@article {pmid41267135,
year = {2025},
author = {Zreik, M and Redding, A and Santarossa, S},
title = {From engagement to evidence: a scoping review of qualitative and quantitative measures of adult patient engagement in research.},
journal = {Research involvement and engagement},
volume = {11},
number = {1},
pages = {136},
pmid = {41267135},
issn = {2056-7529},
support = {SOE-2022C2-28911/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
abstract = {BACKGROUND: Patient engagement in research has been found to improve the quality and relevance of research findings. Quantifying levels of patient engagement may be beneficial in measuring engagement quality, yet tools for this purpose remain scarce. A scoping review was conducted to summarize and analyze existing tools used to measure patient engagement in research for the purpose of assessing the content validity of Hamilton et al.’s Patient Engagement In Research Scale (PEIRS). METHODS: The electronic database Ovid MEDLINE was used to conduct a search related to keywords and controlled vocabulary from 2017 - November 10, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews checklist. Articles were included if they quantitatively or qualitatively measured any outcome of patient engagement in research, exclusively with patients as participants. Data extraction, completed in Microsoft Excel, included the name of the research engagement tool, the type of tool (i.e., questionnaire, survey, or scale), sample size, source, and characteristics, and time frame of data collection. RESULTS: Five articles were ultimately included in this scoping review after an initial search returned 1719 citations. The most common reason for exclusion during the full text review stage was that articles were review articles. Of selected articles that included demographic data, the majority of participants were women and White. Articles highlighted areas for improvement in existing tools, including the need for patient collaboration at each stage of the research process and stronger communication between researchers and patient partners. CONCLUSIONS: Efforts to effectively measure patient engagement in research remain scant. Included studies were limited by inconsistency in defining “patient engagement” and a lack of demographic data collection.},
}

@article {pmid41372737,
year = {2025},
author = {Shah, A and Doshi, G},
title = {Stress and neurodegeneration: mechanistic insights and therapeutic opportunities for preserving brain resilience.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {41372737},
issn = {2240-2993},
abstract = {Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis are strongly influenced by persistent stress, which accelerates both their onset and progression. This review explores the intricate interplay between chronic stressors, oxidative and metabolic imbalances, protein misfolding, inflammatory responses, and psychosocial adversity, and their cumulative impact on the aging brain’s capacity for homeostasis. The loss of cellular resilience due to prolonged stress leads to maladaptive outcomes, including mitochondrial dysfunction, sustained neuroinflammation, breakdown in proteostasis, and disruption of hypothalamic-pituitary-adrenal axis signaling, all of which amplify neuronal vulnerability. The detailed molecular pathways that underlie these phenomena, the article identifies key mediators such as Reactive Oxygen species, mitochondrial regulators, heat shock proteins, and proinflammatory cytokines that drive neurodegeneration. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar up to 2025. Eligible publications included original research articles, clinical studies, and systematic reviews focusing on stress-related molecular pathways, oxidative metabolism, proteostasis, neuroinflammation, and therapeutic interventions in aging and neurodegenerative diseases. A qualitative synthesis of these studies was performed to identify key mechanisms, biomarkers, and emerging treatment strategies relevant to stress-induced neurodegeneration. Further, the review evaluates both established and emerging interventions aimed at mitigating these stress-driven processes. Lifestyle modifications such as aerobic exercise, calorie restriction, and cognitive behavioural therapies complement pharmacological agents like antioxidants, chaperone modulators, and anti-inflammatory drugs to enhance brain resilience and delay disease onset. Recent advances in the field, including integrated multi-omics profiling, biomarker discovery, and medicine approaches, promise to refine our ability to satisfy patients and deliver targeted therapies based on individual stress profiles. Additionally, the article discusses the neuroimmune-gut axis and the potential for interventions targeting microbiome-related inflammation. Early detection of stress-related biomarkers and personalized strategies holds considerable promise for improving clinical outcomes, enabling earlier diagnosis, and fostering tailored therapies that preserve cognitive function and independence in aging populations.},
}

@article {pmid41840453,
year = {2026},
author = {Morgan, TL and Carroll, K and Waqar, A and Hudek, N and Mosa, M and Richards, DP and Meeking, K and Granieri, M and Smith, M and Walz, M and Etherington, C and Marlin, S and Gillies, K and Presseau, J and Brehaut, JC},
title = {A meta-review of patient engagement, shared decision-making, and factors influencing equity-deserving populations' participation in clinical trials.},
journal = {Research involvement and engagement},
volume = {12},
number = {1},
pages = {},
pmid = {41840453},
issn = {2056-7529},
support = {PJT-169055/CAPMC/CIHR/Canada ; PJT-169055/CAPMC/CIHR/Canada ; },
abstract = {BACKGROUND: Many equity-deserving populations, including those facing structural health inequities, lack support to participate in clinical trials while facing barriers to participation. Two approaches—patient engagement (PE) and shared decision-making (SDM)—can help trialists better understand and address such barriers. PE can improve the relevance of trials to silenced communities while SDM can align participation decisions among socially disadvantaged groups with their values, needs, and preferences, which may help overcome health inequities. Further, Indigenous community engagement is vital to address the effects of colonialism and promote Indigenous self-determination and health equity. The extent to which existing reviews have identified common barriers, enablers, and strategies across equity-deserving groups and discussed PE and SDM concepts is unclear. PURPOSE: (1) To describe which equity-deserving populations have been the focus of reviews on clinical trial participation and which barriers, enablers, and strategies are relevant to them (2) to explore the extent to which PE and SDM are discussed in these reviews. METHODS: We searched for English-language reviews (including any study design) summarizing trial participation barriers, enablers, and/or strategies among equity-deserving populations in five peer-reviewed databases. We coded data on the (1) equity-deserving population(s) of focus, (2) barriers, enablers, or interventions/strategies mentioned, (3) PE reported, (4) Indigenous community engagement reported, and (5) SDM outcomes discussed. RESULTS: Findings from 100 reviews showed that some equity-deserving populations have been represented more than others (e.g., 76% on racially, ethnically, culturally, or linguistically diverse populations; 29% on sex and gender populations; 2% on educationally disadvantaged populations). More reviews described barriers (84%) than enablers (31%) or strategies to improve participation (69%). Forty-five reviews (45%) reported PE while 11 (11%) reported Indigenous community engagement. Many reviews (74%) mentioned SDM outcomes (i.e., 9/11 [81.8%] outcomes from Gillies et al.’s internationally agreed core outcome set); however, few reviews (29%) discussed SDM outcomes in detail. CONCLUSIONS: Our findings suggest that PE and SDM could be more broadly applied among multiple equity-deserving groups to better serve disadvantaged communities. We advocate for an expanded focus on less-researched equity-deserving groups, improved PE reporting, prioritization of patient outcomes, and engagement with patients and Indigenous communities.},
}

@article {pmid41863721,
year = {2026},
author = {Maidh, A and Kalra, P and Khan, H and Silakari, P and Grewal, AK},
title = {Circadian disruption as a driver and target in neurodegenerative diseases: from molecular mechanisms to chronotherapeutic strategies.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41863721},
issn = {1573-7365},
abstract = {The Circadian System is a complex network of coordinated clocks that regulates the organism’s internal clock in synchronisation with the outside world. These rhythms are controlled by genetically controlled positive and negative transcriptional-translational feedback loops (TTFL) that generate 24-hour oscillations in the protein level and mRNA of core circadian components. Circadian disruption is recognised as a significant contributor to the molecular pathogenesis of neurodegenerative illnesses, as disease-specific alterations in clock gene expression and melatoninergic signalling have been identified as possible early-stage molecular indicators. Emerging evidence suggests a link between dysregulated circadian rhythms and neurodegenerative diseases, implying that the changes in circadian function may play a critical role in the development and progression of neurodegenerative diseases. The correlation between circadian rhythm and neurodegeneration is highly promising for developing treatment and promoting healthy lifestyle measures. This review article primarily focuses on how abnormalities in circadian rhythms may increase the risk of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Applying knowledge from pre-clinical and translational research on neurodegenerative diseases is crucial for lowering the risks of neurodegeneration and improving the symptoms and quality of life of people with neurodegenerative diseases through approaches that restore circadian rhythm in the context of precision medicine. Understanding this interaction holds promise for developing therapeutic approaches to support a healthy lifestyle.},
}

@article {pmid41894075,
year = {2026},
author = {Kuwar, OK and Tejpal, S and Sharma, V and Sharma, A and Rao, A and Attri, M and Pallavi, and Dhingra, MS},
title = {Therapeutic potential of sulforaphane in neurodegenerative diseases: mechanistic Insights into Nrf2, NF-κB, TrkB, SIRT1, MAPK, and JAK/STAT signalling pathways.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {41894075},
issn = {1573-4978},
abstract = {Neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are chronic and progressive disorders distinguished by neuronal dysfunction, oxidative stress, neuroinflammation, and abnormal protein aggregation. Due to the multifactorial nature of these disorders, current pharmacotherapies provide limited symptomatic relief without altering disease progression. Sulforaphane, a naturally occurring isothiocyanate abundant in cruciferous vegetables like broccoli, has emerged as a potent neuroprotective compound owing to its pleiotropic effects on key cellular signalling pathways. This review provides a thorough overview of the mechanistic insights underlying SFN’s neuroprotective potential, with a focus on the modulation of key signalling pathways such as Nrf2/ARE, NFĸB, BDNF/TrkB, SIRT1, MAPK, and JAK/STAT. Through the activation of antioxidant defenses and suppression of inflammatory cascades, SFN effectively mitigates neuronal damage and supports cellular homeostasis. Preclinical studies consistently demonstrate SFN’s ability to attenuate oxidative stress, inhibit apoptosis, preserve mitochondrial function, and improve neurobehavioral outcomes. While limited clinical evidence supports its safety and bioactivity, further investigations are needed to establish its therapeutic utility in human populations. Overall, SFN represents a promising natural compound with significant potential for the prevention and management of neurodegenerative diseases through multi-targeted pathway modulation.},
}

@article {pmid42009918,
year = {2026},
author = {G Diebo, B and E Nassar, J and Lafage, R and Challier, V and Pesenti, S and Lafage, V},
title = {Distinguishing reactive scoliosis: clinical presentation, pathophysiology and a proposed clinical framework.},
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 = {42009918},
issn = {1432-0932},
abstract = {Purpose: This study introduces "reactive scoliosis" as an umbrella term formalizing various scoliosis subtypes that arise secondary to lumbar disc herniation, spondylolisthesis, and benign tumors. It aims to synthesize current evidence on the clinical presentations, pathophysiology, and surgical management of these subtypes, and to propose a preliminary clinical framework to guide their differentiation and treatment.Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Embase, and Scopus from inception through October 2025, following PRISMA guidelines. Search terms included combinations of "scoliosis" with "lumbar disc herniation", "spondylolisthesis", "osteoid osteoma", "osteoblastoma", and "ganglioneuroma". Studies were included if they addressed pathophysiology, clinical presentation, radiographic features, or surgical outcomes of reactive scoliosis subtypes. Two independent reviewers extracted data on curve magnitude, vertebral rotation, trunk shift, and surgical response.Results: Each reactive scoliosis subtype demonstrates distinct clinical and radiographic characteristics. Spasm scoliosis from lumbar disc herniation presents with short lumbosacral curves, minimal apical rotation, and significant coronal imbalance, typically resolving after discectomy. Pure spasm scoliosis from spondylolisthesis similarly resolves following fusion alone, while olisthetic scoliosis, characterized by vertebral rotation at the slip site rather than the curve apex, requires additional rotational correction. Tumor-driven scoliosis, including osteoid osteomas, osteoblastomas, and ganglioneuromas, demands individualized imaging and surgical strategies, with staged approaches warranted in structurally destructive cases.Conclusion: Accurate identification of reactive scoliosis subtypes is critical for surgical planning. The proposed expanded clinical framework, building upon Guo et al.'s modified Crostelli classification, offers surgeons a structured approach to differentiate these etiologies and optimize management. Prospective studies are needed to validate the algorithm and refine its clinical applicability.Keywords: Reactive scoliosis; Spasm scoliosis; Olisthetic scoliosis; Spondylolisthesis; Lumbar disc herniation},
}

@article {pmid42135015,
year = {2026},
author = {Bate, J and Fealey, J and Young, C and McArdle, A and Staunton, CA and Close, GL},
title = {Sport-related trauma and motor neurone disease: a scoping review of epidemiology, mechanisms and future directions.},
journal = {British journal of sports medicine},
volume = {60},
number = {12},
pages = {900-908},
doi = {10.1136/bjsports-2025-111410},
pmid = {42135015},
issn = {1473-0480},
mesh = {Humans ; *Athletic Injuries/epidemiology/complications ; *Motor Neuron Disease/epidemiology/etiology ; Risk Factors ; *Amyotrophic Lateral Sclerosis/epidemiology ; },
abstract = {OBJECTIVE: To map existing epidemiological evidence assessing the relationship of sport-related trauma and Motor Neurone Disease/Amyotrophic Lateral Sclerosis (MND/ALS), identify potential mechanistic pathways through which athletic exposures may influence disease risk and highlight gaps informing future research priorities.

DESIGN: Scoping Review. Online databases were used to retrieve data from available sources to 25 September 2025.

DATA SOURCES: Published and grey literature in English were identified through searches of ProQuest Central, Web of Science, Scopus, Sport Discus and PubMed. Studies were deemed eligible if they examined MND/ALS in the context of sport-related physical trauma.

METHODS: The scoping review was carried out in accordance with Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A three-step search strategy identified primary studies, secondary literature and grey literature. Following screening, data were extracted using a standardised charting tool to develop a descriptive analysis and thematic synthesis.

RESULTS: The search identified 3307 records, with 45 studies meeting inclusion criteria. General physical activity does not elevate MND/ALS risk; however, professional participation in high-impact sports, particularly those involving repetitive head impacts, has been associated with a 4-15-fold increased risk of MND/ALS. However, current evidence is largely descriptive, correlative and lacks mechanistic insights to verify causation.

CONCLUSION: This scoping review highlights a plausible association between repeated physical trauma in sport and MND/ALS, particularly in professional sports with high exposure to repeated head impacts. Future research should identify biological mechanisms linking trauma exposure with MND/ALS, integrating biomarker, experimental and longitudinal study designs to clarify causal mechanisms and inform risk mitigation in sport.},
}

Humans
*Athletic Injuries/epidemiology/complications
*Motor Neuron Disease/epidemiology/etiology
Risk Factors
*Amyotrophic Lateral Sclerosis/epidemiology

@article {pmid42202831,
year = {2026},
author = {Gorenshtein, A and Omar, M and Barash, Y and Nadkarni, GN and Klang, E},
title = {Large language models integrated into brain-computer interfaces for communication and control: a systematic review.},
journal = {Biomedical physics & engineering express},
volume = {12},
number = {3},
pages = {},
doi = {10.1088/2057-1976/ae737b},
pmid = {42202831},
issn = {2057-1976},
mesh = {*Brain-Computer Interfaces ; Humans ; *Large Language Models ; Electroencephalography ; *Communication ; *Brain/physiology ; Event-Related Potentials, P300 ; },
abstract = {Large language models (LLMs) are starting to be coupled with brain-computer interfaces (BCIs) for assistive communication, but the resulting systems differ widely in where the model sits in the pipeline and in what they actually measure. We performed a systematic review, prepared according to PRISMA, of eleven studies that combine an LLM with a BCI for communication or control. The included work covers P300, SSVEP, cVEP, passive affective and auditory paradigms, and five integration patterns: autocomplete, post-edit correction, intent expansion, dynamic interface generation and affective support. For each study we extracted the hardware and decoding pipeline, the LLM and prompting strategy, latency reporting and outcomes; we used scenario-appropriate metrics rather than a single common metric. Risk of bias was judged with an adapted ROBINS-I framework that stratified studies into online, offline-simulation and system-proposal categories. In the copy-spelling scenario, two studies that measured keystroke savings directly reported values above 50%, with one study exceeding 60% in a multi-turn condition; on an intent-based ALS message-bank task, one online study reached 42 characters per minute with a semantic accuracy of 88%. None of the eleven studies enrolled motor-impaired patients, seven of eleven relied on remote OpenAI endpoints, and reporting of end-to-end latency and failure modes was sparse. We propose a five-category taxonomy of BCI/LLM integration, separate findings that are supported from those that are still speculative, and give a checklist of metrics that should be reported by future studies. The taxonomy and the reporting checklist are the main contributions; clinical benefit for the target population remains to be shown.},
}

*Brain-Computer Interfaces
Humans
*Large Language Models
Electroencephalography
*Communication
*Brain/physiology
Event-Related Potentials, P300

@article {pmid42264545,
year = {2026},
author = {Vishwakarma, H and Chauhan, A and Kaur, L and Awasthi, A},
title = {Nanotechnology-enabled targeting strategies for neurodegenerative disorders: role of functionalized nanoparticles.},
journal = {The Journal of pharmacy and pharmacology},
volume = {78},
number = {6},
pages = {},
doi = {10.1093/jpp/rgag060},
pmid = {42264545},
issn = {2042-7158},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/physiopathology/metabolism ; Animals ; *Nanoparticles ; Blood-Brain Barrier/metabolism ; *Drug Delivery Systems/methods ; Neuroprotective Agents/administration & dosage ; *Nanotechnology/methods ; Oxidative Stress/drug effects ; },
abstract = {BACKGROUND: Neurodegenerative disorders comprise a diverse group of progressive neurological diseases characterized by the gradual loss of neuronal structure and function. Conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis arise from multifactorial mechanisms involving genetic susceptibility, environmental factors, and age-related cellular decline.

PATHOPHYSIOLOGY: Key pathogenic processes include oxidative stress, mitochondrial dysfunction, protein misfolding and aggregation, impaired axonal transport, Golgi fragmentation, and chronic neuroinflammation, all of which disrupt neuronal homeostasis and synaptic communication, ultimately leading to neuronal death. Hormonal imbalances further exacerbate these effects by promoting oxidative damage, inflammation, and metabolic dysfunction.

CHALLENGES IN THERAPY: Despite advances in understanding disease mechanisms, effective drug delivery remains challenging due to the restrictive nature of the blood-brain barrier.

Recent developments highlight the potential of nanoparticle-based drug delivery systems to overcome these limitations. Functionalized nanoparticles enhance blood-brain barrier penetration, improve targeting specificity, and enable controlled drug release. These systems can deliver neuroprotective agents, antioxidants, peptides, and gene therapies directly to affected brain regions. Thus, integrating disease pathophysiology with nanotechnology-based strategies offers a promising approach for improving therapeutic outcomes and advancing precision treatment in neurodegenerative disorders.},
}

Humans
*Neurodegenerative Diseases/drug therapy/physiopathology/metabolism
Animals
*Nanoparticles
Blood-Brain Barrier/metabolism
*Drug Delivery Systems/methods
Neuroprotective Agents/administration & dosage
*Nanotechnology/methods
Oxidative Stress/drug effects

@article {pmid42271589,
year = {2026},
author = {Kunieda, K},
title = {[Clinical Management of Dysphagia and Nutritional Disorders in Neurodegenerative Diseases].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {6},
pages = {695-700},
doi = {10.11477/mf.188160960780060695},
pmid = {42271589},
issn = {1881-6096},
mesh = {Humans ; *Deglutition Disorders/therapy/etiology ; *Neurodegenerative Diseases/complications/therapy ; *Nutrition Disorders/therapy/etiology ; },
abstract = {Dysphagia is common in patients with neuro degenerative diseases. It is associated with aspiration pneumonia, malnutrition, and reduced quality of life. Swallowing assessment should incorporate therapeutic perspectives, including the use of compensatory strategies. In conditions such as amyotrophic lateral sclerosis, weight loss is associated with a poor prognosis, and nutritional therapy may function as a disease-modifying intervention. Clinical ethical issues may arise, including decisions regarding gastrostomy or care for patients with impaired decision-making capacity. A multidisciplinary team approach is essential for managing dysphagia and nutritional problems in these patients.},
}

Humans
*Deglutition Disorders/therapy/etiology
*Neurodegenerative Diseases/complications/therapy
*Nutrition Disorders/therapy/etiology

@article {pmid42283246,
year = {2026},
author = {Fikry, H and Saleh, LA and Sadek, DR},
title = {Histological and Tissue-Level Outcomes of Stem Cell Therapies in Neurodegenerative Disorders: A Systematic Review.},
journal = {Clinical anatomy (New York, N.Y.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/ca.70147},
pmid = {42283246},
issn = {1098-2353},
abstract = {Neurodegenerative diseases, which afflict millions worldwide and threaten public health, have no cure. Neurodegenerative diseases lack effective therapies, burdening society and the economy. Over the past 20 years, regenerative cell therapy (stem cell therapy) has advanced, opening novel neurodegenerative disease treatments. Thus, the current review aimed to systematically highlight experimental and clinical studies of potentially effective therapeutic strategies for stem cells and report histological, cellular, or ultrastructural outcomes following stem cell interventions in neurodegenerative diseases. PRISMA-compliant computerized literature searches of PubMed, Scopus, and Web of Science identified studies on embryonic, induced pluripotent, mesenchymal, or neural stem cells (NSCs) in neurodegenerative disease models and histological and tissue-level outcomes. Search terms included nervous system diseases, histology, neuron regeneration, stem cells, stem cell treatment, and transplantation. Peer-reviewed articles published between 2000 and 2025 were selected. Experimental animal and clinical studies that reported histological or tissue-level results after stem cell treatments were included. Eighty-six studies met the eligibility criteria, covering models of Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease. Across these studies, stem cell therapies were linked to improved neuron survival, better synaptic structure, diminished gliosis, and some restoration of tissue structure. These effects depended on the type of stem cell used, the disease model, and how the treatment was given. Overall, the evidence suggests that stem cell therapies can lead to significant histological and tissue-level improvements in neurodegenerative diseases, supporting their potential for regeneration. Further standardized and translational studies are needed to clarify the underlying mechanisms and improve treatment strategies.},
}

@article {pmid42283497,
year = {2026},
author = {Turner, ED and Twelvetrees, AE},
title = {The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.},
journal = {Journal of neurochemistry},
volume = {170},
number = {6},
pages = {e70496},
pmid = {42283497},
issn = {1471-4159},
support = {220192/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Microtubules/metabolism/physiology ; Animals ; *Neurons/metabolism/physiology ; *Molecular Motor Proteins/metabolism/genetics ; Mutation ; },
abstract = {The extreme morphology and polarised architecture of neurons require the highly sophisticated microtubule transport system for both construction and lifelong survival. Genomic evidence from an expanding landscape of human mutations supports the essential role of the microtubule transport machinery. During neurodevelopment, mutations disrupt the proliferation and migration of neuronal precursors, as well as the initial establishment of polarity. In the mature nervous system, the reliance on microtubule transport shifts to the long-term maintenance of axon integrity and synaptic proteostasis. Across the motor proteins responsible for long distance transport in neurons, mutations highlight a specific vulnerability of long axons to transport failure in Hereditary Spastic Paraplegia (HSP), Charcot Marie Tooth disease Type 2 (CMT2), Spinal Muscular Atrophy (SMA), Perry Syndrome, and Amyotrophic Lateral Sclerosis (ALS) amongst others. Due to the role of microtubule motors in development and maintenance, there is frequently a phenotypic spectrum within a single gene of the microtubule transport system. For example, mutations in dynein motors are linked both to malformations of cortical development and specific motor neuron loss in SMA-LED (Spinal Muscular Atrophy with Lower Extremity Predominance). By synthesising genetic evidence, this review illustrates how specific molecular failures, ranging from motor-domain kinetics to cargo binding, can inform our understanding of neuronal homeostasis. Ultimately, we argue that microtubule transport is not merely a cellular utility, but a key determinant of neuronal longevity.},
}

Humans
*Microtubules/metabolism/physiology
Animals
*Neurons/metabolism/physiology
*Molecular Motor Proteins/metabolism/genetics
Mutation

@article {pmid42285406,
year = {2026},
author = {Mendoza-Camacho, DM and Espinoza-Gutiérrez, HA and Viveros-Paredes, JM and Flores-Soto, ME and Tejeda-Martínez, AR},
title = {Recent advances in neurodegenerative diseases therapeutics: The inhibition of monoacylglycerol lipase strategy.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.06.011},
pmid = {42285406},
issn = {1873-7544},
abstract = {Neurodegenerative diseases share common pathophysiological mechanisms, including chronic neuroinflammation, glutamatergic excitotoxicity, oxidative stress, mitochondrial dysfunction, and disruptions in synaptic and lipid homeostasis. In this context, the endocannabinoid system has emerged as a key modulator of neuroimmune communication and neuronal survival. Within this system, Monoacylglycerol Lipase (MAGL) plays a central role by regulating the levels of the endocannabinoid 2-Arachidonoylglycerol (2-AG) while simultaneously contributing to the generation of arachidonic acid and pro-inflammatory eicosanoids. Pharmacological or genetic inhibition of MAGL increases 2-AG levels and concurrently reduces the biosynthesis of pro-inflammatory lipid mediators, thereby modulating microglial activation, astrocytic responses, and neuronal excitotoxicity. Preclinical studies in models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis consistently demonstrate that MAGL blockade attenuates neuroinflammation, preserves synaptic and neuronal integrity, improves motor and cognitive function, and, in some cases, delays disease progression. Although clinical evidence remains limited, the available data position MAGL as a metabolic convergence point between inflammation and neurodegeneration, suggesting that its modulation may represent a therapeutic strategy with disease-modifying potential.},
}

@article {pmid42287757,
year = {2026},
author = {Jaberi, KR and Haghighi, MR and Aligholi, H and Takallu, S and Asadi, P and Mirzaei, E and Jaberi, AR and Sahraian, A},
title = {Focused ultrasound-mediated nanocarrier delivery across the blood-brain barrier for neurodegenerative diseases.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {201},
number = {},
pages = {119622},
doi = {10.1016/j.biopha.2026.119622},
pmid = {42287757},
issn = {1950-6007},
abstract = {The development of effective therapies for neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis remains a major challenge due to the restrictive nature of the blood-brain barrier (BBB). Conventional systemic drug delivery strategies often fail to achieve sufficient central nervous system (CNS) penetration while avoiding peripheral toxicity. Focused ultrasound (FUS), particularly when combined with microbubbles or nanocarriers, has emerged as a non-invasive approach to transiently and precisely open the BBB, enabling targeted delivery of therapeutics to the brain parenchyma. This review provides a comprehensive overview of the mechanisms by which FUS enhances CNS drug delivery, with a dedicated focus on its integration with nanoparticle-based systems, including liposomes, polymeric nanoparticles, dendrimers, metallic nanoparticles, and exosomes. We discuss how these nanocarriers can be engineered for improved stability, targeting specificity, and stimulus-responsive release upon FUS exposure. Recent advances in ultrasound technology, image guidance (particularly MRI), and therapeutic formulations are summarized, along with preclinical and clinical evidence across key neurodegenerative conditions. Despite promising results, several challenges remain, including long-term BBB stability, regulatory standardization, and scalability for broad clinical application. By integrating principles from acoustics, pharmacology, and nanotechnology, FUS-mediated drug delivery, especially in combination with smart nano systems, represents a significant advancement in precision neurotherapeutics, offering new hope for previously untreatable CNS diseases.},
}

@article {pmid42293743,
year = {2026},
author = {Mavillonio, A and Rizzini, D and Detassis, S and Denti, MA},
title = {Neurodegenerative spliceosomopathies.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1787859},
pmid = {42293743},
issn = {2296-634X},
abstract = {Spliceosomal syndromes are a group of disorders caused by pathogenic variants in core spliceosomal RNAs or proteins, leading to defective pre-mRNA splicing and tissue-specific disease vulnerability. Although the spliceosome is ubiquitously expressed, its dysfunction preferentially affects highly splicing-dependent tissues such as the retina and the nervous system. This mini-review focuses on neurodegenerative spliceosomopathies, including spinal muscular atrophy, amyotrophic lateral sclerosis, and retinitis pigmentosa, highlighting how alterations in snRNP biogenesis, spliceosome assembly, and splicing fidelity drive neuronal and photoreceptor degeneration. We discuss shared and distinct molecular mechanisms, unresolved questions on tissue specificity, and emerging therapeutic strategies targeting RNA splicing.},
}

@article {pmid42295787,
year = {2026},
author = {Zangrando, L and Buratti, E and Paron, F},
title = {TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e76119},
doi = {10.1002/advs.76119},
pmid = {42295787},
issn = {2198-3844},
support = {//AriSLA 2022-NOSRESCUEALS/ ; },
abstract = {TAR DNA-binding protein 43 (TDP-43) is a ubiquitously expressed RNA-binding protein that plays essential roles in RNA metabolism, including transcription, splicing, transport, and stability. Pathological TDP-43 aggregates have become a defining hallmark of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and a large subset of frontotemporal lobar degeneration (FTLD). In the last decade, increasing evidence has challenged the initial thought of TDP-43 condensates as a purely pathological event, highlighting instead the physiological relevance of reversible self-association, polymerization and liquid-liquid phase separation (LLPS) in regulating TDP-43 functions. In this review, we provide an integrated overview of the structural determinants governing TDP-43 two-faced polymerization, with a particular focus on the prion-like domain and its parallelism with prion proteins. Indeed, while physiological assemblies support normal RNA processing, the dysregulation of LLPS by either disease-associated mutations, altered RNA-binding, aberrant post-translational modifications, or proteolytic cleavage can promote the transition toward irreversible, pathogenic aggregates. Finally, we summarize strategies aimed at eliminating TDP-43 aggregates or modulating its phase-separation behavior. Altogether, this review frames TDP-43 polymerization in both healthy and pathological conditions, offering a prion-like centered view of TDP-43 proteinopathies.},
}

@article {pmid42113599,
year = {2026},
author = {Ravits, J and Ferrey, D and Gundogdu, B and Qayoumi, W and Zale, C},
title = {Amyotrophic Lateral Sclerosis: A Review.},
journal = {JAMA},
volume = {335},
number = {22},
pages = {1970-1982},
doi = {10.1001/jama.2026.6385},
pmid = {42113599},
issn = {1538-3598},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/diagnosis/therapy/physiopathology/drug therapy/epidemiology ; Humans ; Superoxide Dismutase-1 ; Riluzole/therapeutic use ; Genetic Therapy ; },
abstract = {IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness due to degeneration of upper motor neurons in the brain and lower motor neurons in the brainstem and spinal cord. It affects approximately 25 000 individuals in the United States.

OBSERVATIONS: Amyotrophic lateral sclerosis is characterized by progressive painless muscle weakness that typically begins in a focal region of the body, such as limb muscle weakness causing hand weakness or foot drop (65%), cranial muscle weakness causing speech or swallowing problems (20%-25%), or axial muscle weakness causing bent posture (5%-10%), and spreads to other body regions over time. The disease usually manifests with dysfunction indicative of both upper motor neurons (causing muscle stiffness and spasticity) and lower motor neurons (causing weakness, fasciculations, atrophy, and flaccidity). After onset, weakness spreads through the musculature and typically causes death due to respiratory muscle weakness. Among people with ALS, approximately 85% have sporadic ALS, which is not associated with known environmental or genetic factors, and 15% have familial ALS. Amyotrophic lateral sclerosis is diagnosed based on clinical features, which can be supported by results of electromyography. More than 60 genes have been associated with ALS, and most are autosomal dominant. Pathogenic variants in chromosome 9 open reading frame 72 (C9orf72) are found in 40% of all familial ALS cases, and pathogenic variants in superoxide dismutase 1 (SOD1) are found in 20% of patients with familial ALS. Patients with ALS survive a mean of 3 to 5 years after diagnosis, and there are currently no curative therapies. Clinical care primarily focuses on symptom management and quality of life. Three US Food and Drug Administration (FDA)-approved disease-modifying therapies are available in the United States. Riluzole and edaravone are oral medications that slow ALS progression by up to 2 to 4 months, and tofersen is an intrathecally administered gene therapy for patients with SOD1 gene variants. Specialized multidisciplinary teams, comprising neurologists, nurses, therapists, dietitians, and social workers, are associated with improved survival (4-7 months) and quality of life.

CONCLUSIONS AND RELEVANCE: Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disorder of upper and lower motor neurons. No curative therapies exist. Two oral medications, riluzole and edaravone, are approved by the FDA and modestly decrease disease progression in sporadic ALS. Tofersen, an intrathecally administered gene-based therapy, is also FDA approved and slows disease progression in patients with SOD1 pathogenic gene variants.},
}

*Amyotrophic Lateral Sclerosis/genetics/diagnosis/therapy/physiopathology/drug therapy/epidemiology
Humans
Superoxide Dismutase-1
Riluzole/therapeutic use
Genetic Therapy

@article {pmid42155417,
year = {2026},
author = {Simpson, J and Zarotti, N},
title = {Distress, not symptoms: Reframing psychological difficulties in neurodegenerative diseases of the motor system.},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
volume = {200},
number = {},
pages = {262-271},
doi = {10.1016/j.cortex.2026.05.004},
pmid = {42155417},
issn = {1973-8102},
mesh = {Humans ; *Neurodegenerative Diseases/psychology ; *Psychological Distress ; *Stress, Psychological/psychology ; *Motor Neuron Disease/psychology ; Huntington Disease/psychology ; Parkinson Disease/psychology ; Anxiety/psychology ; },
abstract = {Psychological distress is common among people living with neurodegenerative diseases of the motor system (NDMS) such as Parkinson's disease, motor neurone disease/amyotrophic lateral sclerosis, and Huntington's disease. Yet the way psychological difficulties are conceptualised in these populations is heavily shaped by medicalised language. Terms such as 'non-motor symptoms' and 'neuropsychiatric manifestations' were originally introduced to draw attention to difficulties beyond movement changes but they now risk positioning mood, anxiety, apathy, and related experiences solely as direct manifestations of neurological degeneration. This framing can obscure the rich psychosocial contexts in which distress arises, blur distinctions between emotional responses and disease processes, and reinforce deficit-based and disease-focused understandings that privilege biological explanations over person-centred ones. It may also influence clinical communication, treatment decisions, help-seeking behaviour, and access to psychological therapy and psychosocial interventions, contributing to inequities in care. This article argues that linguistic choices are not neutral: they construct the boundaries of what counts as legitimate knowledge, shape expectations about causality, and delimit the interventions considered appropriate. Without critical attention to these assumptions, individuals may experience distress as biologically inevitable and clinicians may overlook psychosocial contributors that are amenable to change. We propose that greater awareness of the power of language, coupled with empirical investigation into its effects, is essential for developing a linguistic reformulation of psychological distress in NDMS and more holistic, contextually grounded approaches to supporting psychological wellbeing.},
}

Humans
*Neurodegenerative Diseases/psychology
*Psychological Distress
*Stress, Psychological/psychology
*Motor Neuron Disease/psychology
Huntington Disease/psychology
Parkinson Disease/psychology
Anxiety/psychology

@article {pmid39400020,
year = {2026},
author = {Ali, A and Emad, NA and Sultana, N and Waheed, A and Aqil, M and Sultana, Y and Mujeeb, M},
title = {Navigating into the Paradigm of Nose-to-brain Delivery of Nanotherapeutics and their Repurposing as Nanotheranostics for Neurodegenerative Diseases.},
journal = {CNS & neurological disorders drug targets},
volume = {25},
number = {3},
pages = {174-194},
doi = {10.2174/0118715273319597240927044906},
pmid = {39400020},
issn = {1996-3181},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Drug Repositioning/methods ; *Brain/drug effects/metabolism ; Administration, Intranasal ; *Drug Delivery Systems/methods ; *Theranostic Nanomedicine/methods ; Neuroprotective Agents/administration & dosage ; *Nanoparticles/administration & dosage ; Blood-Brain Barrier/drug effects ; },
abstract = {Repurposing drugs for neurodegenerative diseases using the nose-to-brain route of administration is an intriguing concept with potential benefits. The nose-to-brain route involves delivering drugs directly to the brain via the olfactory or trigeminal pathways, bypassing the blood-brain barrier, which can improve drug efficacy and reduce systemic side effects. Treatment of numerous neurodegenerative diseases such as Multiple sclerosis, Amyotrophic lateral sclerosis, Huntington's, Alzheimer's, and Parkinson's diseases has been attempted using this route of administration. These drugs may include neuroprotective agents, anti-inflammatory drugs, antioxidants, or diseasemodifying therapies. Nanotheranostics, which integrates therapeutic and diagnostic functions in a nanosystem, improves treatment precision and efficacy. Repurposing nanotherapeutics as nanotheranostics for neurodegenerative diseases through the nose-to-brain route of administration holds great potential for both diagnosis and treatment. This review highlights the various mechanisms engaged in transporting nanocarriers from nose-to-brain and the proposed fate of these nanocarriers using different live imaging techniques. Additionally, the discussion covers the recent combinatorial therapeutic approaches and theranostic applications of various nanocarriers used for neurodegenerative diseases through the nose-to-brain. Toxicity to the CNS and nasal mucosa and regulatory considerations about these delivery systems are also deliberated. Overall, repurposed nanoparticles designed as nanotheranostic agents offer a versatile platform for precise diagnosis, targeted therapy, and personalized management of neurodegenerative diseases, holding great promise for improving patient care and advancing our understanding of these complex disorders.},
}

Humans
*Neurodegenerative Diseases/drug therapy
Animals
*Drug Repositioning/methods
*Brain/drug effects/metabolism
Administration, Intranasal
*Drug Delivery Systems/methods
*Theranostic Nanomedicine/methods
Neuroprotective Agents/administration & dosage
*Nanoparticles/administration & dosage
Blood-Brain Barrier/drug effects

@article {pmid42264115,
year = {2026},
author = {Pynn, SR and Jørgensen, H and Vanstone, C and Mosewich, AD and Holt, NL and , },
title = {A narrative scoping review exploring parents' emotion knowledge and abilities in youth sport.},
journal = {Psychology of sport and exercise},
volume = {},
number = {},
pages = {103187},
doi = {10.1016/j.psychsport.2026.103187},
pmid = {42264115},
issn = {1878-5476},
abstract = {The purpose of this narrative scoping review was to explore how parents identify, express, use, understand, and manage their own and others' emotions in the context of youth sport. Mikolajczak's (2009) tripartite model of emotional intelligence (EI) was used as the conceptual lens for this review. Using Levac et al.'s (2010) framework for conducting scoping reviews, we reviewed 87 relevant sport parenting studies and conducted consultation focus groups with 10 sport parents and six former youth athletes. Qualitative data analysis techniques were used to map the findings into themes based on the dimensions of EI (i.e., identification and expression of emotions, using emotions, understanding emotions, and managing emotions). Findings indicated that parents identified and articulated their own emotions and empathised with their children in the sport context. This emotional awareness informed their emotionally supportive behaviours, such as providing encouragement and comfort. Parents' understanding of their children and sport shaped how and when they provided appropriate support in emotional situations. Parents also engaged in efforts to manage their own emotional reactions, drawing on self-awareness and knowledge of the sport environment to regulate their behaviour during competition. These findings provide insight into the specific aspects of youth sport parents' emotional competencies and can be used to inform sport parent education initiatives.},
}

@article {pmid42265532,
year = {2026},
author = {Ella, A and Bar-Kalifa, E},
title = {Relational Memory Reconsolidation: A New Lens on Change Mechanisms in EFT for Couples.},
journal = {Family process},
volume = {65},
number = {2},
pages = {e70172},
pmid = {42265532},
issn = {1545-5300},
mesh = {Humans ; *Interpersonal Relations ; *Memory Consolidation ; Emotions ; *Emotion-Focused Therapy/methods ; *Couples Therapy/methods ; Self Concept ; Memory ; Models, Psychological ; Memory, Episodic ; Male ; },
abstract = {This paper presents a new framework to account for change mechanisms in Emotion-Focused Therapy for Couples (EFT). Building on Lane et al.'s (2015) integrated memory model, the Relational Memory Reconsolidation model described here posits that EFT reshapes partners' relational memory structures through emotionally intense moments of expressed vulnerability and responsiveness. These vulnerability-responsiveness events allow partners to access and transform memories of past relational experiences (i.e., episodic memory) as well as associated beliefs about themselves and the relationship (i.e., semantic memory). This process of emotional activation and reconsolidation allows maladaptive interaction patterns, which are rigid and stressful, to evolve into more adaptive, emotionally responsive exchanges. These emotional moments activate and transform relational self-states that are responsive to interpersonal cues and can shape partners' self-concepts in a relational context. As therapy progresses and emotionally significant interactions are repeated, the coactivation of adaptive and maladaptive self-states updates neocortical memory traces, leading to changes in higher-order relational semantic structures (i.e., the relational self). These moments foster alignment in partners' perceptions of their shared reality, characterized by mutuality in feelings, practices, memories, goals, and identity. Clinically, the framework highlights the need to elicit one partner's core vulnerable emotions and, within the reconsolidation window, disconfirm related expectations (e.g., rejection) through the other partner's empathic and supportive response. This process may transform key components of partners' relational memory, including relational episodic memories, semantic structures, and procedural emotional responses.},
}

Humans
*Interpersonal Relations
*Memory Consolidation
Emotions
*Emotion-Focused Therapy/methods
*Couples Therapy/methods
Self Concept
Memory
Models, Psychological
Memory, Episodic
Male

@article {pmid42268660,
year = {2026},
author = {Roy, É and Blais, M and Dion, P and Rouleau, GA and Dupré, N and Picher-Martel, V},
title = {Oligogenic variants in NEK1 and ATXN2 in amyotrophic lateral sclerosis: report of two cases and review of the literature.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2685158},
pmid = {42268660},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects the upper and lower motor neurons and leads to progressive paralysis. More than 40 genes have been implicated in familial ALS, which represents about 10% of ALS cases. Some genes, including C9orf72, SOD1, FUS and TARDBP are undoubtedly considered causative, but many others have uncertain pathogenicity and low penetrance. Here, we described the cases of two siblings affected by ALS and carrying both an ATXN2 heterozygous 32 CAG trinucleotide repeat expansion and a novel NEK1 heterozygous c.1674_1677dup. The segregation of both variants in this large family with thirteen siblings may support a role for these variants as susceptibility alleles within an oligogenic model. Our review of the literature suggests that NEK1 variants are frequently found in combination with other variants and repeats expansion in the ATXN2 gene appears to be more associated with monogenic ALS, but also frequently combined with C9orf72 repeat expansion.},
}

@article {pmid42274555,
year = {2026},
author = {Khan, MS and Zafar, I and Noman, M and Yang, G and Kang, KS and Bopassa, JC},
title = {Polypharmacology of Pathway Crosstalk in Neurodegenerative Diseases: Chemical Modulation of Interconnected Signaling Networks.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274555},
issn = {2073-4409},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; *Signal Transduction/drug effects ; *Polypharmacology ; Animals ; Oxidative Stress ; Mitochondria/metabolism ; },
abstract = {Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), arise from highly interconnected molecular and cellular abnormalities that progressively lead to neuronal dysfunction, synaptic failure, and cell death. This review provides a unified framework to understand the interrelated molecular mechanisms driving these diseases, with a focus on identifying key disease-specific intervention nodes. Core contributors include oxidative stress, mitochondrial dysfunction, protein aggregation, neuroinflammation, and emerging roles of peroxisomal dysfunction in redox imbalance, lipid dysregulation, and inflammatory amplification. Single-target therapies often show limited efficacy due to the complex, interconnected nature of these pathways. In contrast, polypharmacology, which targets multiple disease-relevant mechanisms simultaneously, offers a more promising therapeutic strategy. This review critically examines how pathway crosstalk drives neurodegenerative progression, with particular emphasis on mitochondrial-ROS-inflammatory signaling, aggregation-proteostasis failure, synaptic-neuroimmune dysfunction, and gut-brain communication. It evaluates various multi-node intervention strategies, including multi-target-directed ligands (MTDLs), molecular hybrids, natural products, drug repurposing, and nanocarrier-based delivery systems. Advances in network pharmacology, artificial intelligence (AI), bioinformatics, and multi-omics have enhanced the identification of actionable therapeutic nodes, candidate compounds, and brain-targeted delivery platforms. Notably, the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathways-play distinct roles in neuroinflammation, amplifying neuronal damage by releasing inflammatory cytokines and inducing mitochondrial dysfunction. However, successful translation into clinical practice remains constrained by challenges such as blood-brain barrier penetration, patient heterogeneity, and biomarker limitations. The review advocates for a shift towards mechanism-informed, patient-stratified polypharmacological strategies to better address the network pathology of neurodegeneration, despite significant translational hurdles.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
*Signal Transduction/drug effects
*Polypharmacology
Animals
Oxidative Stress
Mitochondria/metabolism

@article {pmid42274577,
year = {2026},
author = {Schuldt, ON and Leitch, SR and Jones, LK and Buckley, PR and Morrison, BE},
title = {Neuroinflammatory Remodeling by Type 2 Immune Pathways Links Allergic Signaling to Neurodegenerative Disease.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274577},
issn = {2073-4409},
support = {R15HL165397//National Heart Lung and Blood Institute/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/immunology/pathology ; Animals ; *Signal Transduction/immunology ; *Hypersensitivity/immunology ; *Neuroinflammatory Diseases/immunology ; },
abstract = {The hallmarks of allergic diseases are Type 2 immunity, including IL-4 and IL-13 production, IgE antibody generation, mast cell and basophil activation, histamine release, and eosinophil activation. There are many routes by which such mediators can influence CNS biology, including cytokine entry or signaling via brain barrier receptors; leukocyte trafficking across activated barriers; cytokine signaling via circumventricular organ sites or dural immune compartments; vagus nerve afferent signaling; mast cell degranulation; and histamine neuromodulation. Neuroinflammation is a common hallmark of many neurodegenerative diseases, but whether and to what degree allergic/type 2 immune biology may be involved depends on the specific disease stage and pathology. Here, we assess studies connecting the roles of IL-4/IL-13 signaling, IgE/mast cell activation, eosinophil-attractive chemokines, and histamines in Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, dementia with Lewy bodies, Huntington's disease, prion disease, and tauopathy/atypical parkinsonism. Mechanisms appear most clear in the case of Parkinson's disease, where epidemiology suggests an important role in dementia/Alzheimer's disease, while for other neurodegenerative conditions the evidence is less compelling and may be either mechanistic or modulatory. Confounding issues include sex differences, drug exposures, comorbid conditions, socioeconomic factors, and coexisting inflammatory diseases. Finally, we suggest a strategy based on longitudinal immune phenotyping, CNS biomarkers, and pathway manipulation to assess the relationship between allergic immune signaling and neurodegeneration.},
}

Humans
*Neurodegenerative Diseases/immunology/pathology
Animals
*Signal Transduction/immunology
*Hypersensitivity/immunology
*Neuroinflammatory Diseases/immunology

@article {pmid42274592,
year = {2026},
author = {Sgalletta, B and Agostini, F and Bisaglia, M},
title = {The Role of Iron in Neuronal Homeostasis: A Double-Edged Sword.},
journal = {Cells},
volume = {15},
number = {11},
pages = {},
pmid = {42274592},
issn = {2073-4409},
mesh = {Humans ; *Iron/metabolism ; *Homeostasis ; Animals ; *Neurons/metabolism ; Neurodegenerative Diseases/metabolism/pathology ; Neurogenesis ; Neurodevelopment ; Brain/metabolism ; },
abstract = {Iron is an essential micronutrient that plays a central role in numerous biological processes. Despite its relatively low abundance in the human body, iron is particularly critical for brain function. Systemic and cerebral iron homeostasis is tightly regulated through coordinated mechanisms involving absorption, transport, storage, and recycling. Within the brain, iron metabolism is further controlled by the blood-brain barrier and specialized neural cell populations, including neurons, astrocytes, oligodendrocytes, and microglia. Iron is indispensable for neurodevelopment, supporting neurogenesis, myelination, and neurotransmitter synthesis. However, both iron deficiency and iron overload have detrimental consequences. Early-life iron deficiency disrupts neural development and leads to long-lasting cognitive, motor, and behavioral impairments, whereas excessive iron accumulation promotes oxidative stress, ferroptosis, and neuroinflammation. These mechanisms have been described to contribute to the pathogenesis of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, neurodegeneration with brain iron accumulation, and amyotrophic lateral sclerosis. This review first outlines systemic and brain iron metabolism, highlighting how neural cells regulate homeostasis. Next, it examines iron's physiological roles, particularly in neurogenesis and neurodevelopment. Finally, it explores iron's involvement in neurodegenerative diseases, emphasizing neuroinflammation as a primary mechanism of iron toxicity.},
}

Humans
*Iron/metabolism
*Homeostasis
Animals
*Neurons/metabolism
Neurodegenerative Diseases/metabolism/pathology
Neurogenesis
Neurodevelopment
Brain/metabolism

@article {pmid42274906,
year = {2026},
author = {He, Y and Yi, T and Min, M and Xu, K and Lin, H and Xu, R and Deng, D and Xiao, X},
title = {Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {42274906},
issn = {1995-8218},
abstract = {This review illustrates how environmental stressors disrupt glutamate homeostasis via specific mechanisms: lead-induced thiol modification, manganese mediated yin yang 1 (YY1)-histone deacetylases (HDAC) repression, PM2.5-triggered microglia-astrocyte crosstalk, and advanced glycation end products (AGEs)-receptor for advanced glycation end products (RAGE)-nuclear factor kappa-B (NF-κB) signaling from high-sugar diets. Together with genetic susceptibility and pigment epithelium-derived factor (PEDF), these factors impair astrocytic glutamate uptake, promoting synaptic glutamate accumulation. Subsequent N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor overactivation triggers calcium overload, mitochondrial dysfunction, oxidative stress, and neuroinflammation-termed "degenerative excitotoxicity". Excitotoxicity manifests in Alzheimer's disease (amyloid-beta-excitatory amino acid transporter 2 (EAAT2) interplay), Parkinson's disease (subthalamic nucleus-driven excitatory storm), and amyotrophic lateral sclerosis (astrocytic failure versus neuronal cell-autonomous mechanisms). Future interventions need multi-target strategies, emerging technologies, and lifestyle modifications. This convergent framework offers a unified understanding linking environmental exposure to neurodegeneration and charts a roadmap toward mechanism-based prevention and treatment.},
}

@article {pmid42276614,
year = {2026},
author = {Karthikeyan, K and Velmurugan, G and Upadhyay, R and Sevanan, M and Chinnathambi, S},
title = {Glutamate and glutamine metabolism in neurodegenerative diseases.},
journal = {International review of neurobiology},
volume = {186},
number = {},
pages = {1-24},
doi = {10.1016/bs.irn.2026.01.008},
pmid = {42276614},
issn = {2162-5514},
mesh = {Humans ; *Glutamic Acid/metabolism ; *Glutamine/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; Animals ; },
abstract = {Glutamate is known as the most important excitatory neurotransmitter in brain. Glutamate and glutamine recycling is very essential to maintain the nitrogen metabolism. Despite of its major functions, its dysregulation is a basic pathology which is common to neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS). Amyloid-β and Tau in AD disrupt glutamate uptake and the glutamate-glutamine cycle, accelerating synaptic failure, whereas loss of astrocytic EAAT2 in ALS generates unrelenting excitotoxicity and motor neuron demise. Toxic α-synuclein aggregation in PD exacerbates dopamine-glutamate imbalance through destabilizing corticostriatal transmission. This review explores on the key mechanisms by which glutamate impairment leads to the pathogenies of neurogenerative disorders and also about current medications like amantadine, memantine, and riluzole which are glutamate antagonists, are shown to partially alleviative but cannot halt the advancement of the disease. One of the potential targets for disease-modifying treatments could be the receptor modulation, astrocytic function, and elimination of excess glutamate.},
}

Humans
*Glutamic Acid/metabolism
*Glutamine/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy
Animals

@article {pmid42279231,
year = {2026},
author = {Mesches, MH and Granholm, AC and Paredes, D and Mesches, K and Oguma, Y and Dezawa, M},
title = {Stem Cell Therapy for Parkinson's Disease: A Mechanistically Distinct Role for Muse Cells.},
journal = {Journal of clinical medicine},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/jcm15114370},
pmid = {42279231},
issn = {2077-0383},
abstract = {Cell replacement therapy is a promising investigational approach for Parkinson's disease (PD), a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although current PD therapies provide symptomatic relief, none halt or reverse disease progression. Early transplantation studies using fetal dopaminergic neurons provided proof of concept for PD cell replacement, with recent efforts focusing on pluripotent stem cell-derived dopaminergic progenitors that are now entering clinical testing. These strategies face challenges, however, including immune compatibility, tumorigenic risk, and the need for controlled differentiation and functional integration. Multi-lineage differentiating stress-enduring (Muse) cells are endogenous, non-tumorigenic pluripotent-like stem cells that home to sites of tissue injury and differentiate in response to the host microenvironment. A targeted literature search of PubMed and Scopus, however, did not identify prior reviews specifically addressing Muse cells in the context of PD, highlighting a gap in the literature. Here, we examine current limitations of established cell-replacement approaches and consider whether Muse cells may represent a mechanistically distinct cell source. Early clinical studies of Muse cell therapy in stroke and amyotrophic lateral sclerosis suggest an encouraging safety profile and preliminary signals of potential therapeutic benefit, although these findings are based on small, early-stage trials and require confirmation. The evidence supporting Muse cell therapy in PD is currently limited to a single preclinical animal study, supported by mechanistic in vitro findings and indirect evidence from other neurologic disease models; therefore, its relevance to PD remains to be established, and current evidence is insufficient to support conclusions regarding clinical efficacy. Together, these observations provide a rationale for further targeted preclinical investigation and support the systematic evaluation of Muse cells as a mechanistically distinct candidate for regenerative therapy in PD.},
}

@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 ; Oxidative Stress/radiation effects ; Animals ; *Ultraviolet Rays ; Public Health ; },
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.},
}

Humans
*Neurodegenerative Diseases/radiotherapy/therapy
*Ultraviolet Therapy/methods
Oxidative Stress/radiation effects
Animals
*Ultraviolet Rays
Public Health

@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 = {Humans ; *Artificial Intelligence/standards ; *Decision Support Systems, Clinical/standards ; Intelligent Systems ; },
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.},
}

Humans
*Artificial Intelligence/standards
*Decision Support Systems, Clinical/standards
Intelligent Systems

@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 = {*Metals, Heavy/toxicity ; Humans ; *Environmental Exposure/adverse effects ; Meta-Analysis as Topic ; },
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.},
}

*Metals, Heavy/toxicity
Humans
*Environmental Exposure/adverse effects
Meta-Analysis as Topic

@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 = {*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy ; Humans ; Japan ; *Practice Guidelines as Topic ; Edaravone/administration & dosage ; Genetic Therapy ; *Drug Approval ; Administration, Oral ; Oligonucleotides, Antisense/administration & dosage ; Drug Therapy, Combination ; Consensus ; },
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.},
}

*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy
Humans
Japan
*Practice Guidelines as Topic
Edaravone/administration & dosage
Genetic Therapy
*Drug Approval
Administration, Oral
Oligonucleotides, Antisense/administration & dosage
Drug Therapy, Combination
Consensus

@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/pathology/metabolism ; *Antimicrobial Peptides/immunology/metabolism ; Drosophila ; *Antimicrobial Cationic Peptides/immunology ; },
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.},
}

Animals
Humans
*Neurodegenerative Diseases/immunology/pathology/metabolism
*Antimicrobial Peptides/immunology/metabolism
Drosophila
*Antimicrobial Cationic Peptides/immunology

@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 ; *Perioperative Care/methods ; Hypothalamo-Hypophyseal System/immunology ; *Enhanced Recovery After Surgery ; *Neuroimmunomodulation/physiology ; Pituitary-Adrenal System ; *Transcutaneous Electric Nerve Stimulation/methods ; *Gastrointestinal Tract/surgery/innervation ; Randomized Controlled Trials as Topic ; Treatment Outcome ; *Postoperative Complications/prevention & control ; },
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.},
}

Humans
*Acupuncture Points
Recovery of Function
*Perioperative Care/methods
Hypothalamo-Hypophyseal System/immunology
*Enhanced Recovery After Surgery
*Neuroimmunomodulation/physiology
Pituitary-Adrenal System
*Transcutaneous Electric Nerve Stimulation/methods
*Gastrointestinal Tract/surgery/innervation
Randomized Controlled Trials as Topic
Treatment Outcome
*Postoperative Complications/prevention & control

@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 ; *Motor Cortex/physiology/physiopathology ; Functional Laterality/physiology ; *Evoked Potentials, Motor/physiology ; Movement/physiology ; Pyramidal Tracts/physiology/physiopathology ; },
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.

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.

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.

CONCLUSIONS: Mirror movements can be interpreted within a tri-layer model reflecting distinct disruptions in corticospinal connectivity, interhemispheric inhibition, and supraspinal motor control.

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.},
}

Humans
*Transcranial Magnetic Stimulation/methods
*Movement Disorders/physiopathology
*Motor Cortex/physiology/physiopathology
Functional Laterality/physiology
*Evoked Potentials, Motor/physiology
Movement/physiology
Pyramidal Tracts/physiology/physiopathology

@article {pmid42255170,
year = {2026},
author = {Gurumurthy, NP and Hurley, L and Nezami, BT and Gottfredson O'Shea, N},
title = {Behavior change techniques in mobile health interventions promoting recovery from substances: A synthesis of reviews and meta-analyses.},
journal = {Digital health},
volume = {12},
number = {},
pages = {20552076261458891},
pmid = {42255170},
issn = {2055-2076},
abstract = {OBJECTIVE: This synthesis of reviews and meta-analyses delves into the landscape of behavior change techniques (BCTs) employed in digital interventions designed to help individuals abstain from or reduce consumption of substances (including alcohol, tobacco, and illicit drugs). This review considers the "black box" problem in mHealth programs by using Michie et al.'s BCT taxonomy to describe BCTs that have been used in intervention literature and to explore potential active ingredients that may contribute to intervention effectiveness.

METHODS: We synthesize findings from 49 systematic reviews and meta-analyses. While individual studies often express inconclusiveness for the effectiveness of specific BCTs, this review uncovers promising avenues for future research. Our analysis focuses on mobile health (mHealth) just-in-time adaptive interventions (JITAIs), with a specific emphasis on substance use reduction.

RESULTS: Eleven BCTs were studied extensively in these reviews, including self-monitoring of behavior, feedback on behavior, goal setting, social support, prompts/cues, and behavior substitution. Our synthesis of evidence points to prompts/cues as particularly promising and highlights a handful of BCTs that demand further investigation, including self-monitoring, goal setting, and feedback on behavior.

CONCLUSIONS: This review identifies specific limitations in each step of review formulation and provides nuanced suggestions to enhance the efficacy of future research endeavors.},
}

@article {pmid42257870,
year = {2026},
author = {Nguyen, N and Lauinger, AR and Naik, A and Liu, R and Yolcu, Y and Arnold, PM},
title = {Clinical Research for the Use of 7 T Magnetic Resonance Imaging for Spinal Pathologies: a Scoping Review.},
journal = {Clinical neuroradiology},
volume = {},
number = {},
pages = {},
pmid = {42257870},
issn = {1869-1447},
abstract = {PURPOSE: Magnetic resonance imaging (MRI) at 7 T (7T) offers higher signal-to-noise ratio and improved spatial resolution compared to lower magnetic field strengths such as 1.5T and 3T, which may improve lesion detection and anatomical visualization for spinal cord pathology. This review summarizes current techniques and achievements in 7T spinal imaging and outlines associated technical barriers and future directions.

METHODS: A scoping review in accordance with PRISMA extension for scoping reviews guidelines was performed utilizing PubMed, Scopus, and Web of Science. Only studies related to 7T MRI of human subjects were included, after removing unrelated studies and those of non-human subjects.

RESULTS: Twenty-nine studies were included. Current literature supports 7T's superior resolution and signal-to-noise ratio in comparison to 1.5T and 3T MRI. These studies reported improved lesion detection and staging in multiple sclerosis (MS), spinal cord injury (SCI), and amyotrophic lateral sclerosis (ALS); however, the implications of results are limited by small sample sizes, technical heterogeneity, and inconsistent outcome measures. Additionally, the use of 7T spinal imaging remains limited by radiofrequency coil design, susceptibility artifacts, physiological noise, lack of FDA-clearance for spinal indications, and an absence of standardized imaging protocols. Future research aims to address these limitations.

CONCLUSION: Spinal cord imaging at 7T is challenging due to technical constraints and higher susceptibility to artifacts as a result of physiological noise (respiration, swallowing, and bulk movement). However, early studies' results using 7T imaging support improved ability, compared to 3T, to provide enhanced visualization of fine anatomical structures, such as nerve roots, and to improve spinal cord lesion detection.},
}

@article {pmid42259394,
year = {2026},
author = {Zhang, K and Kong, S and Ma, Y and Kan, C and Zheng, T and Sun, X},
title = {Natural monomer compounds in neurodegenerative diseases: Targeting ferroptosis and neuroinflammation.},
journal = {Behavioural brain research},
volume = {513},
number = {},
pages = {116319},
doi = {10.1016/j.bbr.2026.116319},
pmid = {42259394},
issn = {1872-7549},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss driven by oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Ferroptosis, an iron-dependent and lipid peroxidation-associated form of regulated cell death, has recently been identified as a key contributor to neuronal vulnerability. Emerging evidence demonstrates that purified natural monomer compounds derived from medicinal plants exert potent neuroprotective effects by targeting ferroptosis and neuroinflammatory pathways. Representative agents such as curcumin, baicalin, resveratrol, and ginsenoside Rg1 activate nuclear factor E2-related factor-2 and glutathione peroxidase 4 signaling to preserve redox balance, while suppressing microglia-mediated inflammation through inhibition of toll-like receptor 4 pathways. This review highlights the interplay between ferroptosis and neuroinflammation in NDDs, summarizes the regulatory effects of bioactive herbal monomer compounds, and discusses recent advances in multi-omics profiling, nano-delivery strategies, and translational research. By modulating the ferroptosis-neuroinflammation axis, these compounds may represent promising therapeutic candidates for NDDs.},
}

@article {pmid42261056,
year = {2026},
author = {Bromberg, MB},
title = {The Flail Limb Syndrome.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70307},
pmid = {42261056},
issn = {1097-4598},
abstract = {The flail limb syndrome is primarily a lower motor neuron disorder that initially affects proximal arm muscles (flail arm syndrome-FAS) or distal leg muscles (flail leg syndrome-FLS). Both were recognized early on (1886 for FAS and 1918 for FLS) as somewhat distinct from classic amyotrophic lateral sclerosis (ALS). Descriptions in the literature are case series with limited information on electrophysiologic features (central and peripheral), cognitive involvement, and genetic mutations. What follows is a compilation of these features. The flail limb syndromes are rare, representing ~7%-8% of ALS. They have a higher ratio of males to females compared to classic ALS. Both are defined by predominant focal arm or leg weakness for ~2 years before progression to other regions, although there can be early and mild clinical or electrophysiologic evidence for denervation and reinnervation in other regions during the initial period. Ultimately, there is progression to respiratory failure, but at a slower rate compared to classic ALS. Upper motor neuron clinical signs are variable, but transcortical magnetic stimulation paradigms and magnetic resonance imaging tractography support upper motor neuron loss. Tests of the split hand pattern show it is rare compared to ALS. Dementia is also rare. Genetic testing supports a spectrum of ALS-related gene mutations but at a lower frequency than with classic ALS, and no gene mutation is predominant. Diagnosis requires ~2 years of regional stability to predict the better prognosis for the flail limb syndromes.},
}

@article {pmid42262533,
year = {2026},
author = {Korade, G and Kharat, S and Rathi, K},
title = {Nitric oxide in neuroinflammation and neurodegeneration: dual roles, inflammasome crosstalk, and biomarker opportunities.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42262533},
issn = {1432-1912},
abstract = {Nitric oxide is a short-lived gas that plays a critical role in numerous physiological processes, including vascular regulation, neurotransmission, and immune responses. In the CNS NO's role is complex, as it can both protect and damage neurons. Microglia, the brain's resident macrophages, produce excessive NO in response to stimuli like endotoxins and cytokines, leading to chronic inflammation and neuronal damage associated with neurodegenerative diseases such as Alzheimer's, Parkinson's, multiple sclerosis, and amyotrophic lateral sclerosis. NO's dual role as a pro-inflammatory and anti-inflammatory mediator is intricately linked to its impact on neuronal health and disease progression. This review is aimed at summarizing and critically discussing the roles of NO in neuroinflammation, neurodegeneration, inflammasome regulation, and related therapeutic perspectives. A narrative literature review was conducted using electronic databases (e.g. PubMed and Google Scholar) to identify experimental and clinical studies on NO, neuroinflammation, neurodegenerative diseases, inflammasomes, and related biomarkers and therapies, with emphasis on mechanistic and translational work. Research into NO's effects on inflammasomes, key components of the innate immune system, reveals that NO can inhibit inflammasome activation, influencing inflammatory responses. Despite progress, challenges remain, including the need for cell-type-specific models, advanced technological approaches, and the development of selective NO modulators. Overall, current evidence indicates that NO exerts both neuroprotective and neurotoxic effects in the CNS, mediated by its complex interactions with neural, glial, and immune pathways. Future research should focus on the dual nature of NO, explore lesser-known inflammasomes, and incorporate human-centric models to develop targeted therapies.},
}

@article {pmid42262640,
year = {2026},
author = {Tavassoli, T and Marco, EJ and Puts, N},
title = {Sensory Reactivity in Autism: Integrating Behavioural, Affective, Physiological, and Neural Dimensions.},
journal = {Current psychiatry reports},
volume = {28},
number = {1},
pages = {},
pmid = {42262640},
issn = {1535-1645},
abstract = {PURPOSE OF REVIEW: The goal of this paper is to synthesise recent research on sensory reactivity differences in autism across the lifespan, using He et al.'s sensory taxonomy as an organising framework. The review aims to address how behavioural, affective, perceptual, physiological, and neural levels of processing contribute to sensory reactivity differences, and how these differences relate to broader outcomes such as mental health, adaptive functioning, and quality of life.

RECENT FINDINGS: Across behavioural studies, autistic youth show elevated and variable sensory responsivity, with hypersensitivity predicting internalising symptoms and sensory seeking linked to externalising behaviours. Affective reactivity is consistently elevated across cultures, associated with anxiety and caregiver stress, and sensory seeking may function as a coping mechanism. Psychophysical research reveals domain‑specific perceptual differences-such as reduced tactile adaptation, altered motion noise exclusion, and enhanced pitch discrimination-rather than overarching hyper‑ or hyposensitivity. These perceptual findings often show limited correspondence with questionnaire‑based measures. Physiologically, autonomic dysregulation is implicated, or pharmacological approaches show emerging promise. Neuroimaging evidence highlights excitation-inhibition imbalance and altered connectivity, including dissociations between exogenous and endogenous networks in sensory‑reactive autistic children. Across multiple levels of processing, sensory reactivity differences in autism are robust, heterogeneous, and meaningfully linked to mental health and daily functioning. Key conclusions include: • Sensory hyperreactivity predicts internalising challenges, while sensory seeking may reflect regulatory strategies. • Perceptual differences are domain‑specific • Physiological and neural evidence converges on autonomic dysregulation and differences in connectivity patterns.},
}

@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 ; *Stress Granules/metabolism/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Organelles/metabolism ; Autophagy ; Neurons/metabolism ; },
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].},
}

Humans
*Aging/metabolism/physiology
*Stress Granules/metabolism/physiology
*Neurodegenerative Diseases/metabolism/pathology
Animals
*Organelles/metabolism
Autophagy
Neurons/metabolism

@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/methods ; Forensic Genetics ; *Forensic Sciences/methods ; Genome, Human/genetics ; Gene Frequency/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.},
}

Humans
*Death, Sudden, Cardiac/pathology
*Genomics/methods
Autopsy/methods
Forensic Genetics
*Forensic Sciences/methods
Genome, Human/genetics
Gene Frequency/genetics

@article {pmid42254255,
year = {2026},
author = {Beniwal, SS and Rawat, A and Sharma, N and Calderón, DC and Mwaanga, C and Mora, VA and Saini, P and da Costa, REAR and Mushir Ali, AS and Kumar, A and Dwivedi, A and Mehta, SP and Patel, DR and Danda, P},
title = {Translating potential into practice: the evolving landscape of neural stem cell therapeutics in clinical applications.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {6},
pages = {3284-3295},
pmid = {42254255},
issn = {2049-0801},
abstract = {BACKGROUND: Neural stem cell (NSC) therapeutics have emerged as a promising approach for addressing neurological disorders due to their inherent ability to self-renew, differentiate into neural lineages, and secrete neurotrophic factors.

METHODS: This narrative review explores the evolving clinical landscape of NSC applications, highlighting their therapeutic potential in neurodegenerative diseases, ischemic stroke, and spinal cord injuries.

FINDINGS: Recent clinical advancements demonstrate the safety and preliminary efficacy of NSC-based therapies in conditions like Parkinson's disease and amyotrophic lateral sclerosis. NSCs' capacity to promote neuroplasticity and tissue restoration underscores their potential in reversing synaptic and neuronal damage. Despite these advancements, significant challenges remain. Ethical considerations, particularly concerning cell sourcing and patient consent, must be carefully navigated. Technical barriers, including cell delivery, survival, and long-term integration, require innovative solutions. Furthermore, safety concerns such as tumor formation and immune rejection necessitate rigorous preclinical and clinical assessments. Regulatory challenges, including the standardization of manufacturing processes and international harmonization, are essential for widespread adoption.

CONCLUSION: Looking ahead, the integration of precision medicine, advanced biomaterials, and patient-specific-induced pluripotent stem cells offers promising approaches to enhance NSC therapeutics. Collaborative efforts between researchers, clinicians, and regulatory agencies are crucial for overcoming existing barriers and translating NSC research into clinical practice, offering new hope for patients with complex neurological conditions.},
}

@article {pmid42254864,
year = {2026},
author = {Yokoi, S and Iguchi, Y and Katsuno, M},
title = {Human iPSC-derived motor neurons as a platform for elucidating TDP-43-related amyotrophic lateral sclerosis pathogenesis: a mini review.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1864964},
pmid = {42254864},
issn = {1662-5099},
abstract = {TAR DNA-binding protein 43 (TDP-43) is a major pathogenic RNA-binding protein associated with amyotrophic lateral sclerosis (ALS). Heterozygous mutations in TDP-43 cause familial ALS, known as ALS10. TDP-43 is predominantly localized in the nucleus under physiological conditions. Not only ALS patients with TARDBP mutations but also the majority of sporadic ALS patients exhibit TDP-43 pathology, which is defined by nuclear clearance and cytoplasmic aggregation. The inclusion of cryptic exons in genes such as STMN2 and UNC13A has emerged as a hallmark of TDP-43 loss of function, as demonstrated in TDP-43 knockdown models and postmortem analyses. However, it is not yet clear how TDP-43 levels and location change from healthy to pathological conditions in ALS. Motor neurons derived from induced pluripotent stem cells (iPSCs) have been widely used in ALS research and provide a promising platform to investigate early-stage disease mechanisms. However, challenges remain in generating models that faithfully recapitulate ALS pathogenesis. In this review, we summarize recent advances in TDP-43-related iPSC-derived motor neuron models and discuss future perspectives for elucidating ALS pathogenesis. We propose that longitudinal analyses of TDP-43 dynamics and co-culture systems will be essential to better model early ALS pathogenesis.},
}

@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 = {},
pmid = {41498289},
issn = {1744-1358},
mesh = {*Valosin Containing Protein/metabolism/genetics ; Humans ; *Mitochondria/metabolism ; *Homeostasis ; Animals ; *Adenosine Triphosphatases/metabolism/genetics ; Mitochondrial Proteins/metabolism ; Mitochondria Associated Membranes ; 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.},
}

*Valosin Containing Protein/metabolism/genetics
Humans
*Mitochondria/metabolism
*Homeostasis
Animals
*Adenosine Triphosphatases/metabolism/genetics
Mitochondrial Proteins/metabolism
Mitochondria Associated Membranes
Nuclear Proteins

@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 ; *Neurodegenerative Diseases/metabolism/genetics/enzymology ; *N-Acetylglucosaminyltransferases/genetics/metabolism/antagonists & inhibitors ; *Aging/metabolism/genetics ; Animals ; RNA, Messenger/metabolism/genetics ; RNA Splicing ; },
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.},
}

Humans
*Neurodegenerative Diseases/metabolism/genetics/enzymology
*N-Acetylglucosaminyltransferases/genetics/metabolism/antagonists & inhibitors
*Aging/metabolism/genetics
Animals
RNA, Messenger/metabolism/genetics
RNA Splicing

@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 & dosage ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Animals ; Drug Discovery/methods ; Neuroprotective Agents/pharmacology/administration & dosage ; Drug Development/methods ; Mice, Transgenic ; Disease Models, Animal ; Free Radical Scavengers/pharmacology/administration & dosage ; Oxidative Stress/drug effects ; Mice ; 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.

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.

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.},
}

*Edaravone/pharmacology/administration & dosage
Humans
*Amyotrophic Lateral Sclerosis/drug therapy/physiopathology
Animals
Drug Discovery/methods
Neuroprotective Agents/pharmacology/administration & dosage
Drug Development/methods
Mice, Transgenic
Disease Models, Animal
Free Radical Scavengers/pharmacology/administration & dosage
Oxidative Stress/drug effects
Mice
Blood-Brain Barrier/metabolism

@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.},
}

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

@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.},
}

Humans
*Interleukin-17/metabolism
*Neurodegenerative Diseases/metabolism/pathology/immunology
Animals
*Inflammation/metabolism/pathology
Signal Transduction
Disease Progression
Blood-Brain Barrier/metabolism

@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.},
}

*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

@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.},
}

Humans
*Vesicular Transport Proteins/metabolism/chemistry/genetics
Animals
*Cell Membrane/metabolism

@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 {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.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology
*Frontotemporal Dementia/pathology
*Neuroglia/pathology/metabolism
Animals

@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.

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.

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.

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.

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 {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 & 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 {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.},
}

Humans
*Nerve Growth Factor/therapeutic use
Animals
*Nervous System Diseases/therapy/drug therapy
History, 20th Century
History, 21st Century

@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 & supportive care},
volume = {23},
number = {},
pages = {e85},
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.

OBJECTIVES: To establish the current state of the research literature examining the impact of MND on the couple's relationship.

METHODS: A scoping review was undertaken with thematic analysis used to synthesize the data.

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.

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.},
}

Humans
*Motor Neuron Disease/psychology/complications
*Spouses/psychology
Qualitative Research
Interpersonal Relations
Male
Female
Adaptation, Psychological

@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 {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 = {398},
number = {9},
pages = {11357-11386},
pmid = {40163151},
issn = {1432-1912},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/physiopathology/therapy ; *Mitochondria/drug effects/metabolism/pathology ; Animals ; Oxidative Stress ; },
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.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/physiopathology/therapy
*Mitochondria/drug effects/metabolism/pathology
Animals
Oxidative Stress

@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 = {64},
number = {12},
pages = {1213-1223},
doi = {10.1080/14992027.2025.2477755},
pmid = {40164145},
issn = {1708-8186},
mesh = {Adult ; Child ; Humans ; Communication Barriers ; *Cultural Diversity ; Culturally Competent Care/ethnology ; *Ethnicity/psychology ; Health Knowledge, Attitudes, Practice/ethnology ; Health Literacy ; *Health Services Accessibility ; *Healthcare Disparities/ethnology ; *Persons with Hearing Disabilities/psychology/rehabilitation ; },
abstract = {OBJECTIVE: To conduct a systematic review of identified barriers and facilitators for ethnically diverse adults and children in accessing hearing health services.

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 al.'s conceptual framework of access to healthcare.

STUDY SAMPLE: 25 articles met the inclusion criteria.

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.

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.},
}

Adult
Child
Humans
Communication Barriers
*Cultural Diversity
Culturally Competent Care/ethnology
*Ethnicity/psychology
Health Knowledge, Attitudes, Practice/ethnology
Health Literacy
*Health Services Accessibility
*Healthcare Disparities/ethnology
*Persons with Hearing Disabilities/psychology/rehabilitation

@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/ ; //María 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.},
}

*Conservation of Natural Resources
*Social Network Analysis
*Politics
Cooperative Behavior
Knowledge

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/therapy/metabolism/diagnosis
*Epigenesis, Genetic
Biomarkers/metabolism
DNA Methylation
Animals

@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.},
}

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

@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.

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.

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.

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.},
}

Humans
*Radiofrequency Ablation/adverse effects/methods
*Thyroid Cancer, Papillary/surgery
*Thyroid Neoplasms/surgery
Treatment Outcome
Postoperative Complications/epidemiology/etiology

@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 & biomedicine},
volume = {26},
number = {3},
pages = {368-376},
pmid = {40178484},
issn = {2831-090X},
mesh = {*Amyotrophic Lateral Sclerosis/pathology/diagnosis/metabolism ; Humans ; Biomarkers/metabolism ; *Skin/pathology/metabolism ; Animals ; alpha-Synuclein/metabolism ; },
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.},
}

*Amyotrophic Lateral Sclerosis/pathology/diagnosis/metabolism
Humans
Biomarkers/metabolism
*Skin/pathology/metabolism
Animals
alpha-Synuclein/metabolism

@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.},
}

*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

@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.},
}

*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

@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.},
}

Humans
*Extracellular Vesicles/metabolism
*Translational Research, Biomedical/methods
Biomarkers/metabolism
*Nervous System Diseases/therapy/diagnosis/metabolism
Animals
*Neurology/methods/trends

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/physiopathology/diagnostic imaging
*Neuroimaging/methods
*Brain/pathology/diagnostic imaging
Disease Progression
Spinal Cord/pathology/diagnostic imaging
*Functional Laterality/physiology

@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.},
}

*Copper/metabolism
Humans
*Neurodegenerative Diseases/metabolism
*COVID-19/metabolism
Animals
SARS-CoV-2
Brain/metabolism

@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.},
}

*Neurofilament Proteins/analysis
Humans
Biomarkers/analysis
*Nervous System Diseases/diagnosis/metabolism

@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},
support = {P20 GM109025/GM/NIGMS NIH HHS/United States ; R35 AG071476/AG/NIA NIH HHS/United States ; },
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.},
}

Humans
*Biomarkers/metabolism/blood
*Drug Development/methods
*Neurodegenerative Diseases/drug therapy/diagnosis
Clinical Trials as Topic/methods
Animals
Alzheimer Disease/drug therapy

@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.},
}

Humans
*Autophagy/drug effects
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
Animals
*Protein Aggregates/drug effects
*Protein Aggregation, Pathological/drug therapy/metabolism

@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 & 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.

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.

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.},
}

Humans
*Drug Delivery Systems
*Neurodegenerative Diseases/drug therapy/physiopathology
Oxidation-Reduction
Blood-Brain Barrier/metabolism
Animals
*Central Nervous System Agents/administration & dosage/pharmacokinetics
Brain/metabolism

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*DNA-Binding Proteins/genetics/metabolism
Animals
Mutation
Protein Processing, Post-Translational

@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 & 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.

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.

RESULTS: Our analysis encompassed 22 RCTs involving 138,282 participants (mean age 64.8 years, 36.4% female). Among all investigated medications, only dapagliflozin demonstrated significant prophylactic benefits, specifically in preventing Parkinson's disease (odds ratio = 0.28, 95% confidence intervals = 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.

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.

TRIAL REGISTRATION: PROSPERO CRD42021252381.},
}

Humans
*Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use
Hypoglycemic Agents/pharmacology/therapeutic use
*Neurodegenerative Diseases/prevention & control/drug therapy
Randomized Controlled Trials as Topic
*Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology

@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 = {83},
number = {3},
pages = {2713-2726},
pmid = {40192904},
issn = {1559-0283},
mesh = {*Superoxide Dismutase/metabolism ; Humans ; Animals ; Amyotrophic Lateral Sclerosis/enzymology/metabolism ; Male ; },
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.},
}

*Superoxide Dismutase/metabolism
Humans
Animals
Amyotrophic Lateral Sclerosis/enzymology/metabolism
Male

@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).},
}

Humans
*Black or African American/psychology
Adolescent
Child
*Social Learning
*Students/psychology
*Emotions
Schools

@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 & 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.},
}

Humans
*Gait Disorders, Neurologic/therapy/etiology/diagnosis/physiopathology
*Muscle Spasticity/therapy/complications/physiopathology/diagnosis
*Disease Management

@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.},
}

*Amyotrophic Lateral Sclerosis/drug therapy
Humans
*Edaravone/therapeutic use
*Neuroprotective Agents/therapeutic use
*Free Radical Scavengers/therapeutic use
Disease Progression
Riluzole/therapeutic use

@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.},
}

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

@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.},
}

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

@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 & pharmacotherapy = Biomedecine & 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.},
}

Humans
*Receptor, Cannabinoid, CB2/metabolism/agonists
*Neurodegenerative Diseases/drug therapy/metabolism
Animals
Endocannabinoids/metabolism
Molecular Targeted Therapy
Cannabinoid Receptor Agonists/therapeutic use

@article {pmid40209696,
year = {2025},
author = {Nashwan, AJ and 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 = {34},
number = {5},
pages = {432-442},
pmid = {40209696},
issn = {1423-0151},
mesh = {Humans ; *Myasthenia Gravis/diagnosis/complications/physiopathology/epidemiology/therapy ; *Amyotrophic Lateral Sclerosis/diagnosis/complications/physiopathology/therapy/epidemiology ; Middle Aged ; Aged ; Adult ; Aged, 80 and over ; Male ; },
abstract = {UNLABELLED:

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.

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.

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.

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.

Humans
*Myasthenia Gravis/diagnosis/complications/physiopathology/epidemiology/therapy
*Amyotrophic Lateral Sclerosis/diagnosis/complications/physiopathology/therapy/epidemiology
Middle Aged
Aged
Adult
Aged, 80 and over
Male

@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 {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.},
}

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

@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.},
}

Humans
Animals
*Neurons/pathology/metabolism/physiology
*Stress, Psychological/pathology/metabolism
*Brain/pathology

@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 & 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.},
}

Humans
*Ubiquitins/metabolism
Animals
*Cytokines/metabolism
*Neurodegenerative Diseases/metabolism

@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.},
}

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

@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 = {31},
number = {12},
pages = {1077-1088},
doi = {10.1016/j.molmed.2025.03.008},
pmid = {40234116},
issn = {1471-499X},
mesh = {Humans ; *Phosphoglycerate Kinase/metabolism/genetics/antagonists & inhibitors ; Animals ; *Nervous System Diseases/drug therapy/enzymology/metabolism ; Molecular Targeted Therapy ; Parkinson Disease/drug therapy/metabolism/enzymology ; },
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.},
}

Humans
*Phosphoglycerate Kinase/metabolism/genetics/antagonists & inhibitors
Animals
*Nervous System Diseases/drug therapy/enzymology/metabolism
Molecular Targeted Therapy
Parkinson Disease/drug therapy/metabolism/enzymology

@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.},
}

*Amyotrophic Lateral Sclerosis/therapy/genetics
Humans
*Genetic Therapy/methods/trends
Animals

@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.},
}

Humans
*Alzheimer Disease/metabolism/drug therapy/pathology
Animals
*Interferon Regulatory Factors/metabolism/genetics
*Neuroinflammatory Diseases/metabolism/drug therapy
Signal Transduction
Inflammation/metabolism

@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.},
}

*Caenorhabditis elegans/genetics/metabolism
Animals
*Neurodegenerative Diseases/metabolism/genetics/drug therapy/pathology
*Disease Models, Animal
Humans
Caenorhabditis elegans Proteins/metabolism/genetics

@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 & inhibitors/genetics ; *GPI-Linked Proteins/metabolism/antagonists & 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.},
}

Humans
Animals
*Nervous System Diseases/metabolism/drug therapy
*Nerve Tissue Proteins/metabolism/antagonists & inhibitors/genetics
*GPI-Linked Proteins/metabolism/antagonists & inhibitors/genetics
Molecular Targeted Therapy
Neurodegenerative Diseases/metabolism/drug therapy

@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.

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.

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).

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.

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.},
}

Humans
*Exercise
*Motor Neuron Disease/diagnosis/physiopathology
*Wearable Electronic Devices

@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},
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.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism
*DNA-Binding Proteins/genetics/metabolism
*TDP-43 Proteinopathies/genetics/pathology
*Mutation/genetics

@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 & frontotemporal degeneration},
volume = {26},
number = {7-8},
pages = {605-622},
doi = {10.1080/21678421.2025.2488298},
pmid = {40253599},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/epidemiology/diagnosis ; *Exercise/physiology ; Surveys and Questionnaires ; Reproducibility of Results ; },
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.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/epidemiology/diagnosis
*Exercise/physiology
Surveys and Questionnaires
Reproducibility of Results

@article {pmid40254133,
year = {2025},
author = {Turner-Ivey, B and Jenkins, DP and Carroll, SL},
title = {Multiple Roles for Neuregulins and Their v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog Receptors in Neurodegenerative Disease Pathogenesis and Therapy.},
journal = {The American journal of pathology},
volume = {195},
number = {11},
pages = {2015-2031},
pmid = {40254133},
issn = {1525-2191},
support = {P30 NS057098/NS/NINDS NIH HHS/United States ; P50 AG016582/AG/NIA NIH HHS/United States ; P50 DC000422/DC/NIDCD NIH HHS/United States ; R01 NS109655/NS/NINDS NIH HHS/United States ; },
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 the structural variability of NRG isoforms generated by alternative RNA splicing, the use of multiple promoters and proteolysis, and the impact of this structural variability on neuronal and glial physiology during development and adulthood. We discuss 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 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, we discuss the effects of NRG 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 {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.},
}

*Neurodegenerative Diseases/therapy
Humans
Male
Animals
*Sertoli Cells/transplantation