@article {pmid40905788,
year = {2025},
author = {Willemse, SW and Demaegd, KC and Van Eijk, RPA and Van Damme, P and Harrington, E and Harms, MB and Shneider, NA and Van Rheenen, W and Veldink, JH and Van Den Berg, LH and Van Es, MA},
title = {A VAPB (P56S) mutation in a Dutch patient with familial motor neuron disease: a case report.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2025.2555218},
pmid = {40905788},
issn = {2167-9223},
abstract = {The c.166C > T p.(Pro56Ser) or P56S mutation in the VAPB gene was initially identified as a cause of motor neuron disease in Brazil in a large extended pedigree comprising >1,500 individuals including more than 200 cases. This VAPB mutation gives rise to three phenotypes: late-onset spinal muscular atrophy, classical ALS with bulbar involvement, pyramidal signs and rapid disease progression, and atypical ALS with slow progression. Nearly all known cases originate from a single founder, with most cases outside of Brazil being related to this pedigree. However, there is one report of an independent German family with the same mutation on a different haplotype, indicating a second founder event. Here, we report the first Dutch patient with a P56S mutation in VAPB and motor neuron disease. Documenting rare genetic causes of MND and their natural history are of increasing importance in light of emerging gene-specific therapies.},
}

@article {pmid40905723,
year = {2025},
author = {Peng, C and Maiuri, T and Truant, R},
title = {Tipping the PARylation scale: Dysregulation of PAR signaling in Huntington and neurodegenerative diseases.},
journal = {Journal of Huntington's disease},
volume = {},
number = {},
pages = {18796397251372667},
doi = {10.1177/18796397251372667},
pmid = {40905723},
issn = {1879-6400},
abstract = {Poly(ADP-ribosyl)ation (PARylation), a crucial post-translational modification, is catalyzed by ADP-ribosyltransferases (ARTs) and has significant implications in various cellular processes, including DNA damage response, cell signaling, and immune processes. Aberrant PAR signaling is implicated in numerous neurodegenerative diseases, including Alzheimer, Parkinson, amyotrophic lateral sclerosis, and cerebellar ataxia, where increased PAR levels and PARP1 activity are commonly observed. However, Huntington disease exhibits a unique characteristic: reduced PAR levels and impaired PARP1 activity even in prodromal phase. This finding challenges the prevailing understanding of PAR's role in neurodegeneration and suggests that dysregulation of PAR signaling, whether through overactivation or suppression, can lead to neuronal dysfunction. Herein, we discuss how this balance may impact neurodegenerative diseases, and possible connections between PAR signaling and emerging modifiers of disease onset identified by HD genome-wide association studies (GWAS).},
}

@article {pmid40905633,
year = {2025},
author = {Verdés, S and Navarro, X and Bosch, A},
title = {Targeting Amyotrophic Lateral Sclerosis with Gene Therapy: From Silencing Genes to Enhancing Neuroprotection.},
journal = {Human gene therapy},
volume = {},
number = {},
pages = {},
doi = {10.1177/10430342251372898},
pmid = {40905633},
issn = {1557-7422},
abstract = {Gene therapy is emerging as a transformative approach for treating amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disease. While gene replacement has shown a groundbreaking success in spinal muscular atrophy, the complexity of ALS-due to frequent gain-of-function mutations and a heterogeneous etiology-presents significant challenges. Importantly, approximately 90% of ALS cases are sporadic, with unknown genetic mutation, further complicating patient stratification and therapeutic targeting. As a result, gene therapy strategies must often address multiple pathological mechanisms simultaneously. So far, current gene therapy strategies aim to either suppress toxic gene expression or promote neuroprotection, predominantly via viral-mediated delivery systems. This review will provide an overview of emerging preclinical and clinical gene therapy approaches for ALS, focusing on two main strategies: gene silencing and neuroprotection. Gene silencing techniques, including antisense oligonucleotides (ASOs), viral-mediated RNA interference, and gene editing, have demonstrated efficacy in reducing mutant gene expression, particularly in SOD1 and C9orf72 models, although clinical translation has so far yielded limited success. The recent Food and Drug Administration's approval of the ASO therapy Qalsody for SOD1-ALS underscores the clinical potential of these approaches. Neuroprotective strategies aim to enhance motor neuron survival through delivery of trophic factors, often targeting both central and peripheral tissues to harness retrograde transport mechanisms. We will discuss the advantages and limitations of various delivery vectors, targeting specificity, timing of intervention, and translational challenges, alongside current clinical trial data. This review aims to synthesize how these approaches may converge to address the multifaceted nature of ALS and guide the development of next-generation therapeutics.},
}

@article {pmid40905501,
year = {2025},
author = {Huang, Y and Wan, Y and Chen, J and Qin, M and Wang, J and Liang, H},
title = {Knowledge mapping of biomarkers in amyotrophic lateral sclerosis: a comprehensive bibliometric and visual analysis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17582024.2025.2554525},
pmid = {40905501},
issn = {1758-2032},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease, and there is currently an urgent need to identify valuable biomarkers to accelerate diagnosis, optimize treatment and prognosis.

METHODS: To conduct a bibliometric analysis of publications related to "ALS biomarker" over the past 20 years, utilizing the subject search feature of the Web of Science Core Collection along with CiteSpace, VOSviewer, and Bibliometrix.

RESULTS: This review presents a 20-year bibliometric analysis of ALS biomarker research (2004-2024), analyzing 2535 publications showing rising trends. The United States led contributions, with Turner, Martin R as the most productive/cited author. Key research hotspots included cerebrospinal fluid, tdp-43, clinical trial, and neuroinflammation. Topics such as neurofilament light chain, machine learning, and exosomes could potentially represent the cutting edge of future research.

CONCLUSION: In summary, this study uses bibliometric analysis of ALS biomarker research to provide a forward-looking perspective on its future limitations and potential.},
}

@article {pmid40904817,
year = {2025},
author = {Kuo, T and Reynolds, T and Chen, L and Park, C and Rascati, K and Godley, P},
title = {Racial and ethnic disparities in ALS: a longitudinal electronic health records study.},
journal = {Therapeutic advances in neurological disorders},
volume = {18},
number = {},
pages = {17562864251365001},
pmid = {40904817},
issn = {1756-2856},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options and significant variability in care. Racial and ethnic disparities in ALS management and outcomes have been reported, but findings remain inconsistent.

OBJECTIVES: This study aimed to evaluate racial and ethnic disparities in ALS care, specifically differences in healthcare utilization, treatment patterns, and survival, within a large healthcare system.

DESIGN: This retrospective cohort study analyzed electronic health records from a large healthcare system in Texas for patients diagnosed with ALS between 2013 and 2023, examining racial and ethnic differences in treatment and outcomes.

METHODS: Patients were identified using International Classification of Diseases (ICD) codes. Baseline characteristics, including race/ethnicity and socioeconomic factors, were collected. Primary outcomes included the use of noninvasive ventilation (NIV), tracheostomy, gastrostomy, mobility aids, and ALS medications; secondary outcomes included time to diagnosis and survival. Racial and ethnic disparities were assessed using generalized linear regression and Cox proportional hazards models, adjusting for demographic and socioeconomic factors.

RESULTS: A total of 636 patients were included (74.5% Non-Hispanic White, 5.3% Non-Hispanic Black, 7.4% Hispanic, and 12.7% Other). Non-Hispanic Black patients had significantly higher tracheostomy rates than Non-Hispanic White patients (35.3% vs 8.7%; adjusted odds ratio (OR), 6.20; 95% confidence interval (CI), 2.43-15.84). Hispanic patients had lower odds of receiving riluzole (42.6% vs 61.8%; adjusted OR, 0.36; 95% CI, 0.18-0.71) and higher rates of emergency department visits (adjusted OR, 2.00; 95% CI, 1.09-3.65) and hospitalizations (adjusted OR, 2.57; 95% CI, 1.37-4.81). No significant racial or ethnic differences were observed in time to diagnosis or survival after adjustment.

CONCLUSION: Significant racial and ethnic disparities exist in ALS care, particularly in tracheostomy utilization, medication prescribing, and healthcare access. These findings underscore the need for targeted interventions to promote equitable ALS management, including provider education and improved healthcare accessibility.},
}

@article {pmid40904199,
year = {2025},
author = {Isik, S and Osman, S and Yeman-Kiyak, B and Shamshir, SRM and Sanchez, NME},
title = {Advances in Neurodegenerative Disease Therapy: Stem Cell Clinical Trials and Promise of Engineered Exosomes.},
journal = {CNS neuroscience & therapeutics},
volume = {31},
number = {9},
pages = {e70577},
doi = {10.1111/cns.70577},
pmid = {40904199},
issn = {1755-5949},
mesh = {Humans ; *Exosomes/transplantation/metabolism ; *Neurodegenerative Diseases/therapy ; Animals ; *Stem Cell Transplantation/methods/trends ; *Clinical Trials as Topic/methods ; },
abstract = {AIM: This review provides a systematic evaluation of 94 stem cell clinical trials to treat neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease.

METHODS: Data were collected from using relevant search terms, focusing exclusively on stem cell therapy. Of the 8000+ participants in these trials, nearly 70% were enrolled in AD-related studies. Only three Phase 3 studies were conducted, and most trials were in the early phases (Phases 1 and 2). Mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, and embryonic stem cells are used the most to treat neurodegenerative diseases. This review also explores the emerging fields of preclinical and clinical investigations of stem cell-derived exosome-based therapies for neurodegenerative diseases.

RESULTS: Exosomes can cross the blood-brain barrier to deliver therapeutic molecules directly to the brain, offering a less invasive alternative to stem cell transplantation. Mesenchymal stem cell-derived exosomes, in particular, have demonstrated significant potential in preclinical models by reducing neuroinflammation, oxidative stress, and promoting neuronal regeneration. Additionally, recent advances in exosome engineering, including surface modifications, therapeutic agent loading, and transgenic modifications, have improved targeting, stability, blood-brain barrier delivery, and neural cell interactions, enabling targeted and effective treatment. Exosome-based therapies are in the preliminary phases of clinical investigation, with only three clinical trials.

CONCLUSION: Given the increasing interest in exosome therapy, clinical investigations are expected to increase. This growth will be driven by ongoing advancements in exosome technology, a deeper understanding of their therapeutic potential, and escalating demand for innovative treatment strategies for neurodegenerative diseases.},
}

Humans
*Exosomes/transplantation/metabolism
*Neurodegenerative Diseases/therapy
Animals
*Stem Cell Transplantation/methods/trends
*Clinical Trials as Topic/methods

@article {pmid40903966,
year = {2025},
author = {Abbassi, Y and Fink, D and Cei, F and Niccolai, E and Amedei, A},
title = {TDP-43-immunity-microbiota axis in amyotrophic lateral sclerosis: A potential pathogenic mechanism.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00440},
pmid = {40903966},
issn = {1673-5374},
abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease marked by progressive motor neuron degeneration. Despite extensive research, effective treatments remain elusive, underscoring the need to explore the molecular mechanisms driving disease progression. The amyotrophic lateral sclerosis complexity is further compounded by its large heterogeneity, encompassing both genetic and sporadic forms, diverse phenotypic presentations, and highly variable progression rates. A key pathological feature of amyotrophic lateral sclerosis is the aggregation of TAR DNA-binding protein 43, which contributes to cellular toxicity, neuroinflammation, and neuronal dysfunction. This review explores the complex interplay between TAR DNA-binding protein 43 pathology, immunity dysregulation, and the gut-brain axis, with a focus on the role of microbiome-derived metabolites in amyotrophic lateral sclerosis. Neuroinflammation, mediated by both innate and adaptive immunity, plays a central role in disease pathogenesis, with TAR DNA-binding protein 43 influencing immune signaling and exacerbating neurotoxicity. Additionally, disruptions in gut microbiota composition and intestinal barrier integrity, frequently observed in amyotrophic lateral sclerosis patients, suggest a potential role for the gut-brain axis in modulating neurodegenerative processes. By integrating evidence from emerging studies, our aim is to clarify how TAR DNA-binding protein 43 aggregation contributes to neuroinflammation and immune dysfunction while exploring the gut microbiota role as both a modulator and potential biomarker of disease. Understanding these interactions could pave the way for novel therapeutic strategies, including microbiome-targeted interventions such as probiotics, dietary modifications, or immune-modulating therapies. Finally, unraveling the TAR DNA-binding protein 43-immune system-microbiome axis may offer new avenues for personalized treatments aimed at mitigating neuroinflammation, slowing amyotrophic lateral sclerosis progression, and improving patient outcomes and life quality.},
}

@article {pmid40903965,
year = {2025},
author = {Parikh, A and Cholavaram, A and Chitti Babu, AK and Deepankumar, K and Vijayan, M},
title = {Role of voltage-dependent anion channel 1 in neurodegeneration: Mechanisms, implications, and therapeutic potential.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00368},
pmid = {40903965},
issn = {1673-5374},
abstract = {Voltage-dependent anion channel 1 is an integral outer membrane protein of the mitochondria that governs apoptosis, enables metabolite exchange, and influences mitochondrial activity. In neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and Alzheimer's disease, oxidative stress, neuroinflammation, and mitochondrial dysfunction are frequent features. Voltage-dependent anion channel 1 is a key regulator of these processes. This review described the structure, membrane topology, and physiological function of voltage-dependent anion channel 1 in neurons and glial cells. We emphasize how it affects mitophagy, oxidative damage, and changes in mitochondrial permeability. Special attention is focused on how voltage-dependent anion channel 1 interacts with pathogenic proteins that damage mitochondrial integrity and cause neurotoxicity, including mutant huntingtin, phosphorylated tau, α-synuclein, amyloid-beta, and TAR DNA-binding protein 43. Furthermore, the paper examines the function of voltage-dependent anion channel 1 in astrocytic dysfunction and microglial activation, highlighting its impact on neuroinflammation. In a nutshell, we assess treatment strategies that target voltage-dependent anion channel 1, such as VBIT-4, a selective inhibitor of voltage-dependent anion channel 1 oligomerization, and newer methods, including structure-based drug design and CRISPR/Cas9 regulation. Improved knowledge of the hinter voltage-dependent anion channel 1 of the molecular mechanism may allow for new therapeutic approaches in neurodegenerative diseases.},
}

@article {pmid40903956,
year = {2025},
author = {Chen, Y and Yin, P and Chen, Q and Zhang, Y and Tang, Y and Jin, W and Yu, L},
title = {Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00274},
pmid = {40903956},
issn = {1673-5374},
abstract = {Neurodegenerative diseases are a class of disorders with the gradual loss of the central nervous system and peripheral nervous system. Neurodegenerative diseases manifest primarily as cognitive and behavioral disorders that adversely affect the lives of millions of people worldwide. Therefore, it is necessary to elucidate the mechanism of neurodegenerative diseases further and find effective new therapies. In recent years, increasing evidence has shown that the immune system plays a significant role in the pathophysiology of neurodegenerative diseases and regulates this process. The central and peripheral immune systems exert different roles in the disease progression. The development of neurodegenerative diseases is influenced by interactions between them. This review focuses on how the immune system, including microglia mediated nucleotide-binding oligomerization domainlike receptor protein 3 inflammation activation and T cell-mediated neuroinflammation, interactions with neurodegenerative diseases by modulating protein aggregation and blood-brain barrier permeability. Besides, we gave particular attention to glial cell-centered multicellular interactions and the inflammatory signaling pathway. Insight into the immune system's functions and cellular interactions is essential for progressing disease research. In addition, the functions and mechanisms of these immune cells also suggest new ideas and targets for treatment. Therefore, this review summarizes some of the existing treatment strategies for amyloid-beta, tau, neuroinflammation, α-synuclein, associated microbiota, immune modulation, and neural injury repair. In addition, this review summarizes and compares animal models of different common neurodegenerative diseases and clinical research progress. In view of the current research status, new research directions and suggestions are proposed.},
}

@article {pmid40903950,
year = {2025},
author = {Liu, Y and Tang, T and Cai, H and Liu, Z},
title = {Bidirectional communication between the gut microbiota and the central nervous system.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00434},
pmid = {40903950},
issn = {1673-5374},
abstract = {In recent years, an increasing number of researchers have become interested in the bidirectional communication between the gut microbiota and the central nervous system. This communication occurs through the microbiota-gut-brain axis. As people age, the composition of the gut microbiota undergoes considerable changes, which are now known to play an important role in the development of many neurodegenerative diseases. This review aims to investigate the complex bidirectional signaling pathways between the gut and the brain. It summarizes the latest research findings on how the gut microbiota and its metabolites play critical roles in regulating inflammation, maintaining gut health, and influencing the development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The review also analyzes the current clinical applications of gut microbiota-based treatments for neurological disorders, including fecal microbiota transplantation, probiotics, and prebiotics. Many studies show that the gut microbiota affects the brain in several ways. For example, it can produce substances such as short-chain fatty acids and activate inflammatory pathways. Studies involving animals and laboratory models have demonstrated that adjusting the gut microbiota can help improve behavior and reduce neurological problems. Recent metagenomic and metabolomics studies have shown that the microbiota plays a crucial role in maintaining the organism's health. Microorganisms primarily colonize the gut and are involved in host nutrient metabolism, maintaining the structural integrity of the intestine, preserving the intestinal mucosal barrier, and modulating the immune system. The gut microbiota communicates with the brain through a bidirectional microbiota-gut-brain axis. The composition of the gut flora changes considerably with age, and ecological dysregulation has been recognized as one of the twelve most recent hallmarks of aging. Recent studies have linked these changes to a variety of age-related neurological disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, and Huntington's disease. Specifically, the gut microbiota influences the brain through the production of key metabolites such as short-chain fatty acids and the activation of inflammatory and other relevant signaling pathways. In preclinical studies, targeted modulation of the gut microbiota, through methods such as fecal microbiota transplantation, probiotics, and prebiotics, has demonstrated potential in improving host behavioral outcomes. Therefore, gut microbiotabased treatments offer new hope for the treatment of nervous system diseases. However, due to the complexity of the gut microbiota and the potential adverse reactions associated with these therapies, researchers need to carefully assess their safety and efficacy before widespread clinical application.},
}

@article {pmid40903937,
year = {2025},
author = {Martinez, P and van Zundert, B and Bustos, FJ},
title = {Reevaluating the role of skeletal muscle in amyotrophic lateral sclerosis pathogenesis: Insights from muscle-derived factors.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00567},
pmid = {40903937},
issn = {1673-5374},
}

@article {pmid40903936,
year = {2025},
author = {Shao, N and Zhang, X and Ge, Y and Tang, J and Gao, H and Si, W and Cai, B},
title = {O-GlcNAcylation: A molecular switch linking brain health to neurodegeneration.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00101},
pmid = {40903936},
issn = {1673-5374},
abstract = {Neurodegenerative disorders are typically caused by harmful protein accumulation and nerve cell damage. A post-translational modification called O-linked N-acetylglucosamine ylation acts as a critical regulator in these disorders by controlling protein behavior, cell signaling, and energy balance. This modification is dynamically balanced through the cooperative actions of O-linked N-acetylglucosamine transferase and O-GlcNAcase. In healthy brains, O-GlcNAcylation supports nerve cell function and survival, but its imbalance contributes to disease progression. Notably, the effects of O-GlcNAcylation differ across disorders. This review reveals how O-GlcNAcylation bridges molecular mechanisms to neurodegeneration, as well as the prospects of targeted O-linked N-acetylglucosamine acylation therapy for neurodegenerative diseases. In Alzheimer's disease, it blocks toxic changes in key proteins like tau and amyloid-beta. In Parkinson's disease, it reduces the clumping of alpha-synuclein, yet may disrupt dopamine production. In amyotrophic lateral sclerosis, it protects nerve fiber transport systems. Additionally, O-GlcNAcylation plays an indispensable part in other neurodegenerative conditions, including Huntington's disease, aging, Machado-Joseph disease, multiple sclerosis, and giant axonal neuropathy. New therapies targeting this mechanism include glucosamine supplements and O-GlcNAcase inhibitors, which show clinical promise but face translational challenges.},
}

@article {pmid40903652,
year = {2025},
author = {Koyuncu, S and Dominguez-Canterla, Y and Alis, R and Salarzai, N and Petrovic, D and Flames, N and Vilchez, D},
title = {The aging factor EPS8 induces disease-related protein aggregation through RAC signaling hyperactivation.},
journal = {Nature aging},
volume = {},
number = {},
pages = {},
pmid = {40903652},
issn = {2662-8465},
support = {VI742/4-2//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; EXC 2030-390661388//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 0.22.2.030MN//Fritz Thyssen Stiftung (Fritz Thyssen Foundation)/ ; CIAICO/2022/195//Generalitat Valenciana (Regional Government of Valencia)/ ; },
abstract = {Aging is a major risk factor for neurodegenerative diseases associated with protein aggregation, including Huntington's disease and amyotrophic lateral sclerosis (ALS). Although these diseases involve different aggregation-prone proteins, their common late onset suggests a link to converging changes resulting from aging. In this study, we found that age-associated hyperactivation of EPS8/RAC signaling in Caenorhabditis elegans promotes the pathological aggregation of Huntington's disease-related polyglutamine repeats and ALS-associated mutant FUS and TDP-43 variants. Conversely, knockdown of eps-8 or RAC orthologs prevents protein aggregation and subsequent deficits in neuronal function during aging. Similarly, inhibiting EPS8 signaling reduces protein aggregation and neurodegeneration in human cell models. We further identify the deubiquitinating enzyme USP4 as a regulator of EPS8 ubiquitination and degradation in both worms and human cells. Notably, reducing USP-4 upregulation during aging prevents EPS-8 accumulation, extends longevity and attenuates disease-related changes. Our findings suggest that targeting EPS8 and its regulatory mechanisms could provide therapeutic strategies for age-related diseases.},
}

@article {pmid40903341,
year = {2025},
author = {Vedula, P and Ishizuka, K and Hayashida, A and Sueo, K and Sawa, A},
title = {Stress-induced nuclear GAPDH: Scientific update and clinical application.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {},
number = {},
pages = {e00725},
doi = {10.1016/j.neurot.2025.e00725},
pmid = {40903341},
issn = {1878-7479},
abstract = {Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is known as a moonlighting protein beyond its original glycolytic function. Stress-induced nuclear translocation of GAPDH has been reproducibly reported, which results in variety types of cellular responses, including cell death and dysfunction. Blocking this stress-induced cascade has been regarded as a target of drug discovery and development for human disease conditions, particularly for neurological and psychiatric diseases. There are promising small compounds that can block this cascade in cell and animal models. Nevertheless, the clinical trials for Parkinson's disease and amyotrophic lateral sclerosis with one of these compounds Omigapil were unsuccessful. Including these failure cases, this review article discussed the scientific frontline of GAPDH, particularly stress-induced nuclear GAPDH, and its potential for clinical applications.},
}

@article {pmid40903205,
year = {2025},
author = {Ng, L and Sweeney, KD and Mercer, SW},
title = {Challenges in reducing the 10-item CARE measure to a two-item version: comparison of patients' preferences with psychometric evaluation in a cross-sectional survey in Scotland.},
journal = {BJGP open},
volume = {},
number = {},
pages = {},
doi = {10.3399/BJGPO.2025.0085},
pmid = {40903205},
issn = {2398-3795},
abstract = {BACKGROUND: The Consultation and Relational Empathy (CARE) Measure is a widely used 10-item measure to assess patients' perceptions of physician empathy. Takahashi et al.'s (2022) recent study proposed a two-item version based on psychometric evaluation of survey responses, without considering patient preferences.

AIM: To apply Takahashi et al's psychometric method to UK data, and compare findings with patients' preferences on the two most important items.

DESIGN AND SETTING: In 2022, a cross-sectional postal survey of 6,291 Scottish adults was conducted.

METHOD: Using Takahashi et al..'s method, psychometric evaluation compared correlations between all possible two-item combinations with the original 10-item CARE measure to identify the optimal two-item combination. Patients were also asked to select the two items they considered most important. Descriptive analysis examined the proportion of patients selecting each item, and level of agreement on the most popular two-item combination.

RESULTS: 1053 (17%) of 6,291 patients responded. Psychometric evaluation identified items 6 ("Showing care and compassion") and 8 ("Explaining things clearly") as the optimal two-item combination (Cronbach's alpha=0.916, correlation=0.953). This differed from patient preferences, with items 3 ("Really listening") and 8 receiving the highest proportion of votes (19% and 17%, respectively). Preferences also varied by age, deprivation level, and consultation complexity. The most popular two-item combination (items 3 and 8) was selected by 10% of respondents, with 90% selecting other combinations.

CONCLUSION: The psychometrically optimal two-item combination did not align with patient preferences. Given variation in patient preferences and low agreement, reducing the CARE Measure to two-items may be inadvisable.},
}

@article {pmid40902435,
year = {2025},
author = {Midya, V and Bello, G and Andrew, AS and Re, DB and Stommel, EW and Arora, M},
title = {Dysregulation of hair-strand-based elemental biodynamics in amyotrophic lateral sclerosis.},
journal = {EBioMedicine},
volume = {119},
number = {},
pages = {105907},
doi = {10.1016/j.ebiom.2025.105907},
pmid = {40902435},
issn = {2352-3964},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a rare motor neurodegenerative disorder and is predominantly diagnosed in older adults. Altered levels of essential and toxic elements have been implicated in ALS pathophysiology; however, little is known about the longitudinal biodynamic patterns of these elements in patients with ALS.

METHODS: Using a single individual hair strand, we generated time series data of 400-800 time points approximately at 2 to 4 hourly resolution on 17 elemental intensities in ALS-positive cases and ALS-negative controls from a national collection and a regional centre in the US (on a total sample of 391, with 295 cases and 96 controls, with median age at hair collection over 60 years). The elements included were Li, Mg, P, S, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, Sn, Ba, and Pb. We analysed the growth increments in single hair strands using laser ablation-inductively coupled plasma-mass spectrometry to create time-resolved signals of elemental exposure and intensity along the hair strand. Two complementary information-theoretic methods, cross-recurrence quantification analysis and transfer entropy-based network analysis, were employed to generate time-resolved features that quantify the synchronisation of multi-element biodynamics.

FINDINGS: Male ALS-positive cases had significantly lower synchronicity in Cu-Zn temporal biodynamics than ALS-negative controls (recurrence: log(β) = -1.64, p-value < 0.001, q-value = 0.03). Female ALS-positive cases had lower synchronicity in Cr-Ni temporal biodynamics than ALS-negative controls (recurrence: log(β) = -1.59, p-value < 0.001, q-value = 0.46). In both males and females, multiple centrality measures of Cu (that quantify the importance of Cu within a network of all elemental intensities) were significantly lower in ALS-positive cases than in ALS-negative controls [in males, closeness centrality of Cu: log(β) = -0.64, p-value = 0.002, q-value = 0.04; in females, eigenvector centrality of Cu: log(β) = -0.53, p-value = 0.02, q-value = 0.97].

INTERPRETATION: We demonstrate that ALS-positive cases have significantly higher odds of collapse in the synchronisation of elemental biodynamics and worse connectedness in copper-based networks compared to ALS-negative controls.

FUNDING: US National Institutes of Health (P30ES023515, R01ES026033, U2CES030859, U2CES026561, R35ES030435, UL1TR004419, 1OT2NS136938-01, 1R01ES034133-01) and CDC/ATSDR (R01TS000331, R01TS000324 and R01TS000285).},
}

@article {pmid40901987,
year = {2025},
author = {Sun, Z and Li, C and Leitner, D and Wu, M and Zhang, J and Wisniewski, T and Ge, Y},
title = {Age-related Vascular Alterations in the Choroid Plexus: Novel Insights from Pathophysiology and Imaging Studies.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.0735},
pmid = {40901987},
issn = {2152-5250},
abstract = {The choroid plexus (ChP), a highly vascularized brain structure responsible for cerebrospinal fluid (CSF) production, undergoes significant age-related changes that may contribute to neurodegenerative diseases involving disrupted immune regulation, fluid homeostasis and waste clearance. Compared to other brain regions, vascular research on the ChP remains limited despite its critical role as a central interface between the blood and CSF. This review focuses on age-related vascular and structural alterations in the ChP from both histopathological and neuroimaging perspectives, and explores their impact on CSF dynamics, immune regulation, and the integrity of the blood-CSF barrier (BCSFB). Rather than shrinking, the aging ChP often enlarges due to dystrophic changes, as shown in volumetric MRI studies. Histological studies reveal epithelial degeneration, basement membrane thickening, and stromal fibrosis in the normal aging process. In dementia such as Alzheimer's disease (AD), proteomic studies have identified upregulation of AD- and immune-related proteins, along with downregulation of proteins linked to CSF clearance and metabolic support. Emerging high-resolution contrast-enhanced MRI techniques now allow in vivo visualization of microvascular changes within the ChP, shedding light on its normal and abnormal aging processes. Understanding these alterations is critical, as they may influence the onset and progression of various neurological diseases such as AD, Parkinson's disease (PD), normal pressure hydrocephalus, and amyotrophic lateral sclerosis (ALS). The recent advancements and challenges described in this study underscore the need for deeper investigation into ChP aging to inform future diagnostic and therapeutic strategies of neurodegenerative diseases.},
}

@article {pmid40901879,
year = {2025},
author = {Sun, G and Li, X and Hu, J and Yang, T and Liu, C and Wang, Z and Li, D and Xu, W},
title = {De novo design of protein binders to stabilize monomeric TDP-43 and inhibit its pathological aggregation.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {36},
pages = {e2505320122},
doi = {10.1073/pnas.2505320122},
pmid = {40901879},
issn = {1091-6490},
support = {2020YFA0909200//MOST | National Key Research and Development Program of China (NKPs)/ ; 32101181//MOST | National Natural Science Foundation of China (NSFC)/ ; 32494764//MOST | National Natural Science Foundation of China (NSFC)/ ; 92353302//MOST | National Natural Science Foundation of China (NSFC)/ ; 32170683//MOST | National Natural Science Foundation of China (NSFC)/ ; 82188101//MOST | National Natural Science Foundation of China (NSFC)/ ; 22425704//MOST | National Natural Science Foundation of China (NSFC)/ ; 22JC1410400//Science and Technology Commission of Shanghai Municipality (STCSM)/ ; JCYJ-SHFY-2022-005//Chinese Academy of Sciences, Shanghai Branch (ä¸ç§'院上海分院)/ ; },
mesh = {*DNA-Binding Proteins/metabolism/chemistry/genetics ; Humans ; *Protein Aggregation, Pathological/metabolism ; Protein Aggregates ; Protein Binding ; Amyotrophic Lateral Sclerosis/metabolism/genetics ; Amyloid/metabolism/chemistry ; Frontotemporal Lobar Degeneration/metabolism ; Protein Stability ; },
abstract = {Pathological aggregation of transactive response DNA binding protein of 43 kDa (TDP-43), primarily driven by its low-complexity domain, is closely associated with various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite the therapeutic potential of preventing TDP-43 aggregation, no effective small molecule or biomacromolecule therapeutics have been successfully developed so far. Here, we introduce a protein design strategy that yields de novo designed proteins capable of stabilizing the key amyloidogenic region of TDP-43 in its native helical conformation with nanomolar binding affinity. The binding mechanism was further characterized by the NMR and mutagenesis study. More importantly, we demonstrated that our designed protein binders efficiently reduced TDP-43 amyloid aggregation both in vitro and in cells. Our work provides a strategy for designing protein stabilizer of the native conformation of pathological proteins for preventing its amyloid aggregation, shedding light on the development of potential therapeutic approaches for ALS, FTLD, and other protein aggregation-associated diseases.},
}

*DNA-Binding Proteins/metabolism/chemistry/genetics
Humans
*Protein Aggregation, Pathological/metabolism
Protein Aggregates
Protein Binding
Amyotrophic Lateral Sclerosis/metabolism/genetics
Amyloid/metabolism/chemistry
Frontotemporal Lobar Degeneration/metabolism
Protein Stability

@article {pmid40901491,
year = {2025},
author = {Igarashi, K and Ohue, M},
title = {Protein-ligand affinity prediction via Jensen-Shannon divergence of molecular dynamics simulation trajectories.},
journal = {Biophysics and physicobiology},
volume = {22},
number = {3},
pages = {e220015},
doi = {10.2142/biophysico.bppb-v22.0015},
pmid = {40901491},
issn = {2189-4779},
abstract = {Predicting the binding affinity between proteins and ligands is a critical task in drug discovery. Although various computational methods have been proposed to estimate ligand target affinity, the method of Yasuda et al. (2022) ranks affinities based on the dynamic behavior obtained from molecular dynamics (MD) simulations without requiring structural similarity among ligand substituents. Thus, its applicability is broader than that of relative binding free energy calculations. However, their approach suffers from high computational costs due to the extensive simulation time and the deep learning computations needed for each ligand pair. Moreover, in the absence of experimental ΔG values (oracle), the sign of the correlation can be misinterpreted. In this study, we present an alternative approach inspired by Yasuda et al.'s method, offering an alternative perspective by replacing the distance metric and reducing computational cost. Our contributions are threefold: (1) By introducing the Jensen-Shannon (JS) divergence, we eliminate the need for deep learning-based similarity estimation, thereby significantly reducing computation time; (2) We demonstrate that production run simulation times can be halved while maintaining comparable accuracy; and (3) We propose a method to predict the sign of the correlation between the first principal component (PC1) and ΔG by using coarse ΔG estimations obtained via AutoDock Vina.},
}

@article {pmid40901333,
year = {2025},
author = {Agrawal, H and Gupta, N},
title = {Deep learning models for pathological classification and staging of oesophageal cancer.},
journal = {World journal of clinical oncology},
volume = {16},
number = {8},
pages = {109893},
doi = {10.5306/wjco.v16.i8.109893},
pmid = {40901333},
issn = {2218-4333},
abstract = {This letter comments on Wei et al's study applying the Wave-Vision Transformer for oesophageal cancer classification. Highlighting its superior accuracy and efficiency, we discuss its potential clinical impact, limitations in dataset diversity, and the need for explainable artificial intelligence to enhance adoption in pathology and personalized treatment.},
}

@article {pmid40901171,
year = {2025},
author = {Budha, B and Chapagain, A and Adhikari, D and Bajracharya, S and Poudel, D and Budha, R and Adhikari, S and Gurmaita, RK},
title = {Acquired hemophilia a in a female with minimal change disease and hypothyroidism: a rare case report.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {9},
pages = {6168-6172},
doi = {10.1097/MS9.0000000000003645},
pmid = {40901171},
issn = {2049-0801},
abstract = {INTRODUCTION: Juvenile amyotrophic lateral sclerosis (J-ALS) is extremely rare neurodegenerative motor neuron disorder that begins in early childhood or adolescence, before the age of 25 years old. It is characterized by gradual disease progression with comparison to adult-onset ALS and is often linked to genetic mutations.

CASE PRESENTATION: A 16-years-old female presented with long history of generalized weakness since age of 10 years, followed by bilateral sensorineural hearing loss, bulbar symptoms, and limb spasticity. Neurological examination revealed upper motor neuron signs in upper limbs, lower motor neuron signs in lower limbs, and bulbar involvement. Nerve conduction test was normal however, MRI showed early degenerative changes, and diagnosed with J-ALS after careful evaluation. She was started on Riluzole. Despite ICU care and supportive interventions including PEG and tracheostomy, she succumbed to respiratory failure.

DISCUSSION: Rarity, atypical presentation, and finical constraints can delay diagnosis of J-ALS. However, early diagnosis after careful evaluation of clinical symptoms, medical history, electrophysiological and imaging studies followed by prompt treatment with Riluzole and supportive interventions can help prolong survival and improve quality of life.

CONCLUSION: J-ALS is a rare motor neuron disease which possess immense diagnostic challenges, can exhibit relentless progression over short period of time with time.},
}

@article {pmid40901053,
year = {2025},
author = {Satapathy, P and Mehta, R and Sah, R},
title = {Comment on "Clinical Significance of Biochemical Pregnancy Loss in Recurrent Pregnancy Loss Patients: Insights From Euploid Embryo Transfers Minimizing Embryonic Bias".},
journal = {Reproductive medicine and biology},
volume = {24},
number = {1},
pages = {e12674},
doi = {10.1002/rmb2.12674},
pmid = {40901053},
issn = {1445-5781},
abstract = {This commentary addresses Kuwabara et al.'s study on biochemical pregnancy loss (BPL) in recurrent pregnancy loss (RPL) patients following euploid embryo transfers. While their methodology minimizes embryonic bias and strengthens maternal factor assessment, concerns regarding statistical interpretation and potential ascertainment bias limit generalizability. Nonetheless, this study raises important questions regarding the incorporation of BPL into RPL diagnostic frameworks.},
}

@article {pmid40900744,
year = {2025},
author = {Mani, S and Wasnik, S and Shandilya, C and Srivastava, V and Khan, S and Singh, KK},
title = {Pathogenic synergy: dysfunctional mitochondria and neuroinflammation in neurodegenerative diseases associated with aging.},
journal = {Frontiers in aging},
volume = {6},
number = {},
pages = {1615764},
pmid = {40900744},
issn = {2673-6217},
abstract = {The term "neurodegenerative diseases" (NDDs) refers to a range of aging-associated conditions, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Unique clinical symptoms and underlying pathological mechanisms distinguish each of these illnesses. Although these conditions vary, they share chronic neuroinflammation as a defining characteristic. Protein aggregation and mitochondrial dysfunction are believed to play a role in initiating the neuroinflammatory response and, subsequently, the development and course of these illnesses. Apart from providing energy to the cells, mitochondria are involved in the immunoinflammatory response associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and epilepsy. This involvement is attributed to controlling processes such as inflammasome activation and cell death. Under inflammatory conditions, the underlying regulatory mechanisms for these aging-associated disorders may include calcium homeostasis imbalance, mitochondrial oxidative stress, mitochondrial dynamics, and epigenetics. Various NDDs are linked to neuroinflammation and mitochondrial dysfunction. The linkages between these occurrences are becoming more apparent, but the etiology of these pathologic lesions is yet to be elucidated. This review examines the role of neuroinflammation and mitochondrial dysfunction in the growth and course of NDDs, emphasizing the possibility of identifying novel therapeutic targets to address aging-related neurodegenerative processes and retard the progression of these illnesses.},
}

@article {pmid40900615,
year = {2025},
author = {Lee, Y and Park, MJ},
title = {Response to Li et al.'s Letter to the Editor Regarding "Do Skin Prick Tests Predict Nasal Provocation Test Outcomes in Allergic Rhinitis Patients?".},
journal = {International forum of allergy & rhinology},
volume = {},
number = {},
pages = {},
doi = {10.1002/alr.70029},
pmid = {40900615},
issn = {2042-6984},
}

@article {pmid40899661,
year = {2025},
author = {Atici Endes, E and Sherratt, JA and Gerisch, A},
title = {The Effect of Cell Adhesion on the Interpretation of Scratch Assay Data: A Non-Local Model.},
journal = {Mathematical medicine and biology : a journal of the IMA},
volume = {},
number = {},
pages = {},
doi = {10.1093/imammb/dqaf010},
pmid = {40899661},
issn = {1477-8602},
abstract = {Scratch assays are affordable methods developed for sampling wound healing in a laboratory setting. Thanks to these assays, it is possible to investigate the dynamical structure of cell migration and proliferation, which play a central role in the healing process of the wound. Johnston et al. (BMC Systems Biology 9:38, 2015) use scratch assay data to estimate migration and proliferation parameters in a Fisher-type model. The present study is a new attempt to interpret the same data using a non-local continuum approach that incorporates cell-cell adhesion. The non-local part of our model includes two different force functions representing different types of cell adhesion. Using these functions, we estimate the parameters involved in the diffusive and adhesive motion. The original and our model give similarly good agreement with the experimental data for their respective (optimal) parameter sets but the estimated diffusion coefficients differ significantly between both sets. Consequently, Johnston et al.'s data, and thus their experimental methodology are incapable of providing guidance on the effect of cell-cell adhesion in wound healing.},
}

@article {pmid40898684,
year = {2025},
author = {Zhu, Y and Bai, J and Wang, H and Li, M and Yang, F and Pang, X and Du, R and Zhao, J and Huang, X and Cui, F},
title = {The difference between cystatin C- and creatinine-based estimated glomerular filtration rate and survival in amyotrophic lateral sclerosis: a population-based cohort study.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/17582024.2025.2554224},
pmid = {40898684},
issn = {1758-2032},
abstract = {OBJECTIVES: We investigated the relationship between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) and amyotrophic lateral sclerosis (ALS) outcomes.

METHODS: We enrolled ALS patients diagnosed between January 2014 and December 2019. Experienced neurologists followed up the participants until January 2022. Absolute difference between eGFR (eGFRabdiff) and relative difference between eGFR (eGFRrediff) were obtained. Cox proportional hazard models were used to evaluate the relationship between eGFRdiff and ALS survival.

RESULTS: Negative eGFRabdiff were common in the patients (74.7%). For each SD increase of eGFRabdiff, the risk of poor prognosis for ALS patients decreased by 1.9% (HR, 0.981; 95% CI, 0.973-0.989). For each 10% increment in eGFRrediff, the risk of poor prognosis for ALS patients decreased by 17.7% (HR, 0.823; 95% CI, 754-0.898).

CONCLUSIONS: We found that large eGFRdiff was associated with poor prognosis in ALS. Monitoring eGFRdiff in ALS population facilitates prognostic stratification assessment and precise management.},
}

@article {pmid40898457,
year = {2025},
author = {Peng, S and Ouyang, J and Liu, Y and Wang, L and Liu, R},
title = {Causal effect of infectious mononucleosis on neurodegenerative diseases: A Mendelian randomization study.},
journal = {Medicine},
volume = {104},
number = {35},
pages = {e44145},
doi = {10.1097/MD.0000000000044145},
pmid = {40898457},
issn = {1536-5964},
support = {2019YFE0117100//the National key research and development program of China/ ; 82104603//the National Natural Science Foundation of China/ ; 82074174//the National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Infectious Mononucleosis/complications/genetics/epidemiology/virology ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics/virology/etiology/epidemiology ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Alzheimer Disease/genetics ; Parkinson Disease/genetics ; Multiple Sclerosis/genetics ; },
abstract = {Neurodegenerative diseases (NDs) are common chronic diseases with unknown etiology, and the association between virus and its pathogenesis is not clear. The aim of this study is to explore the role of virus in the pathogenesis of NDs by analyzing the causal effect between infectious mononucleosis (IM) mainly caused by Epstein-Barr virus and NDs. Based on the summary statistics of a large-scale genome-wide association study, we analyzed the causal effects of IM and NDs by Mendelian randomization (MR) using genetic variants as instrumental variables, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis. The reliability and stability of the MR analysis results were assessed by the MR-Egger intercept test, MR-PRESSO test, and heterogeneity test. Twenty-two single nucleotide polymorphisms that were significantly and strongly associated with IM were used as instrumental variables in the MR analysis. Inverse variance weighted as the main method of MR analysis shows that there were significant causal effects between IM and Alzheimer disease (OR: 1.037, 95% CI: 1.006-1.070) and Parkinson disease (OR: 0.964, 95% CI: 0.930-1.000), while IM was not significantly associated with amyotrophic lateral sclerosis (P = .269) and multiple sclerosis (P = .182). Sensitivity analyses showed that the results were robust. This study suggests that EB virus may contribute to the pathogenesis of NDs, and more research is needed to explore the specific mechanism of virus action on NDs.},
}

Humans
*Infectious Mononucleosis/complications/genetics/epidemiology/virology
Mendelian Randomization Analysis
*Neurodegenerative Diseases/genetics/virology/etiology/epidemiology
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Alzheimer Disease/genetics
Parkinson Disease/genetics
Multiple Sclerosis/genetics

@article {pmid40898454,
year = {2025},
author = {Alharthi, S and Jafri, SA and Alzaedi, MA and Aljaed, NM and Eldoskey, MM and Abosabie, SAS and Oshi, M and Abosabie, SA and Kamal, NM},
title = {Multisystem inflammatory syndrome in children (MIS-C) presenting with valvulitis, myocarditis, and QTc prolongation: A case report from Saudi Arabia.},
journal = {Medicine},
volume = {104},
number = {35},
pages = {e43995},
doi = {10.1097/MD.0000000000043995},
pmid = {40898454},
issn = {1536-5964},
mesh = {Humans ; Female ; Child ; *COVID-19/complications/diagnosis/therapy ; *Myocarditis/etiology/diagnosis ; Saudi Arabia ; *Systemic Inflammatory Response Syndrome/diagnosis/complications/therapy ; *Long QT Syndrome/etiology/diagnosis ; Electrocardiography ; Diagnosis, Differential ; SARS-CoV-2 ; Echocardiography ; },
abstract = {RATIONALE: This case report highlights the complex clinical course and successful multidisciplinary management of a pediatric patient with multisystem inflammatory syndrome in children (MIS-C), who posed clinical dilemma at presentation. It underscores the ongoing clinical relevance of MIS-C as a post-Coronavirus disease 2019 sequelae and emphasizes the importance of maintaining a high index of suspicion for MIS-C in pediatric differential diagnoses, especially when symptoms overlap with other common conditions.

PATIENT CONCERNS: An 11-year-old previously healthy Saudi girl presented with gastrointestinal symptoms initially suggestive of acute appendicitis. Her condition rapidly deteriorated with signs of cardiovascular compromise.

DIAGNOSES: Surgical exploration confirmed a perforated appendix. Cardiac workup revealed elevated troponin levels, corrected QT interval prolongation (500 ms), ST-segment changes, and echocardiographic evidence of mitral and aortic regurgitation with reduced ejection fraction, leading to a diagnosis of MIS-C fulfilling both Centers for Disease Control and Prevention and World Health Organization criteria. Schwartz et al's criteria are widely accepted for diagnosing long QT syndrome, which guided our interpretation of the corrected QT interval prolongation observed in this case. According to the Centers for Disease Control and Prevention, MIS-C is defined by a constellation of symptoms occurring in individuals under 21 years with recent severe acute respiratory syndrome coronavirus 2 infection or exposure.

INTERVENTIONS: Management included intravenous immunoglobulin, corticosteroids, inotropes, diuretics, aspirin, and broad-spectrum antibiotics, coordinated by a multidisciplinary care team.

OUTCOMES: The patient experienced full cardiac recovery, confirmed through serial electrocardiogram and echocardiography over 1 year.

LESSONS: This case underscores the importance of recognizing MIS-C in children presenting with atypical symptoms such as abdominal pain. Timely diagnosis and early multidisciplinary intervention are essential to prevent serious cardiac complications.},
}

Humans
Female
Child
*COVID-19/complications/diagnosis/therapy
*Myocarditis/etiology/diagnosis
Saudi Arabia
*Systemic Inflammatory Response Syndrome/diagnosis/complications/therapy
*Long QT Syndrome/etiology/diagnosis
Electrocardiography
Diagnosis, Differential
SARS-CoV-2
Echocardiography

@article {pmid40898372,
year = {2025},
author = {Augur, ZM and Fogo, GM and Arbery, MR and Stern, AM and Benoit, CR and Hsieh, YC and Young-Pearse, TL},
title = {Optineurin deficiency disrupts phosphorylated tau proteostasis and clusterin expression in human neurons.},
journal = {Acta neuropathologica communications},
volume = {13},
number = {1},
pages = {188},
pmid = {40898372},
issn = {2051-5960},
support = {F31AG082393-03//NIA Ruth L. Kirschstein Predoctoral Individual National Research Service Award/ ; K00AG079793//NIA Pathway to Independence Award/ ; R01AG055909//NIH Grant/ ; },
mesh = {Humans ; *Neurons/metabolism/pathology ; *Membrane Transport Proteins/deficiency ; *Cell Cycle Proteins/deficiency ; *tau Proteins/metabolism ; *Alzheimer Disease/metabolism/pathology/genetics ; *Clusterin/metabolism ; Induced Pluripotent Stem Cells/metabolism ; *Proteostasis/physiology ; Phosphorylation ; *Transcription Factor TFIIIA/deficiency/genetics ; Female ; Autophagy ; Male ; Brain/metabolism/pathology ; Astrocytes/metabolism ; Aged ; },
abstract = {Optineurin (OPTN) is an autophagy adaptor protein involved in selective autophagy, including aggrephagy and mitophagy. Pathogenic mutations in OPTN have also been linked to amyotrophic lateral sclerosis, frontotemporal dementia, and glaucoma, supporting its role in the etiology of neurodegenerative diseases. Despite its established biological roles, knowledge about its potential contribution to Alzheimer's disease (AD) pathology and neuronal functioning is lacking. AD is characterized by the accumulation of extracellular amyloid-β plaques and intracellular phosphorylated tau (pTau) tangles, with dysfunction in the autophagy-lysosomal pathway exacerbating tau pathology and impairing proteostasis. To investigate the role of OPTN in neuronal proteostasis and AD, we utilized induced pluripotent stem cell-derived neuron (iN) and astrocyte (iA) models. Analyses revealed a significant negative correlation between OPTN and specific pTau epitopes in neurons, as well as a decrease in OPTN protein abundance in brain tissues of individuals with AD. Given these findings, we generated OPTN knockout (KO), heterozygous, and wildtype iNs and iAs using CRISPR/Cas9 editing of iPSCs in two genetic backgrounds. Loss of OPTN in iNs increased specific pTau proteoforms without substantially affecting autophagy processes or mitochondrial respiration. Despite no clear effect on mitochondrial function, several mitochondrial proteins, including OXCT1, were enriched in an unbiased analysis of the OPTN interactome in iNs, as well as proteins involved in intracellular trafficking. Proteomic analyses further identified intracellular clusterin, an AD risk gene, as significantly upregulated in OPTN KO iNs, suggesting OPTN may influence its intracellular processing. Our model system demonstrates modest roles for OPTN in certain neuronal biological processes and potential implications for AD pathogenesis. These findings also suggest that OPTN may exhibit functional redundancy with other autophagy adaptor proteins in human neurons, leading to relatively mild phenotypic changes with complete loss of OPTN.},
}

Humans
*Neurons/metabolism/pathology
*Membrane Transport Proteins/deficiency
*Cell Cycle Proteins/deficiency
*tau Proteins/metabolism
*Alzheimer Disease/metabolism/pathology/genetics
*Clusterin/metabolism
Induced Pluripotent Stem Cells/metabolism
*Proteostasis/physiology
Phosphorylation
*Transcription Factor TFIIIA/deficiency/genetics
Female
Autophagy
Male
Brain/metabolism/pathology
Astrocytes/metabolism
Aged

@article {pmid40898360,
year = {2025},
author = {Scholl, LS and Demleitner, AF and Riedel, J and Adachi, S and Neuenroth, L and Meijs, C and Tzeplaeff, L and Caldi Gomes, L and Galhoz, A and Cordts, I and Lenz, C and Menden, M and Lingor, P},
title = {Identification and validation of a tear fluid-derived protein biomarker signature in patients with amyotrophic lateral sclerosis.},
journal = {Acta neuropathologica communications},
volume = {13},
number = {1},
pages = {187},
pmid = {40898360},
issn = {2051-5960},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnosis ; Male ; Female ; Middle Aged ; Biomarkers/metabolism ; Aged ; *Tears/metabolism ; Adult ; Machine Learning ; Cohort Studies ; Proteomics ; *Eye Proteins/metabolism ; },
abstract = {The diagnosis of Amyotrophic Lateral Sclerosis (ALS) remains challenging, particularly in early stages, where characteristic symptoms may be subtle and nonspecific. The development of disease-specific and clinically validated biomarkers is crucial to optimize diagnosis. Here, we explored tear fluid (TF) as a promising ALS biomarker source, given its accessibility, anatomical proximity to the brainstem as an important site of neurodegeneration, and proven discriminative power in other neurodegenerative diseases. Using a discovery approach, we profiled protein abundance in TF of ALS patients (n = 49) and controls (n = 54) via data-independent acquisition mass spectrometry. Biostatistical analysis and machine learning identified differential protein abundance and pathways in ALS, leading to a protein signature. These proteins were validated by Western blot in an independent cohort (ALS n = 51; controls n = 52), and their discriminatory performance was assessed in-silico employing machine learning. 876 proteins were consistently detected in TF, with 106 differentially abundant in ALS. A six-protein signature, including CRYM, PFKL, CAPZA2, ALDH16A1, SERPINC1, and HP, exhibited discriminatory potential. We replicated significant differences of SERPINC1 and HP levels between ALS and controls across the cohorts, and their combination yielded the best in-silico performance. Overall, this investigation of TF proteomics in ALS and controls revealed dysregulated proteins and pathways, highlighting inflammation as a key disease feature, strengthening the potential of TF as a source for biomarker discovery.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/diagnosis
Male
Female
Middle Aged
Biomarkers/metabolism
Aged
*Tears/metabolism
Adult
Machine Learning
Cohort Studies
Proteomics
*Eye Proteins/metabolism

@article {pmid40897992,
year = {2025},
author = {Quigley, SE and Quigg, KH and Goutman, SA},
title = {Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.},
journal = {CNS drugs},
volume = {},
number = {},
pages = {},
pmid = {40897992},
issn = {1179-1934},
support = {R01NS120926/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01TS000344/ACL/ACL HHS/United States ; R01TS000327//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons. ALS is classically characterized by painless progressive weakness, causing impaired function of limbs, speech, swallowing, and respiratory function. The disease is fatal within 2-4 years, often the result of respiratory failure. The pathologic hallmark for a majority of ALS cases is aberrant cytoplasmic accumulations of the nuclear protein TAR-DNA binding protein (TDP-43). A total of 10-15% of ALS can be attributed to a single gene mutation, known as genetic or "familial" ALS, while the remainder of cases are termed nongenetic or "sporadic" although heritability has been measured in up to 37% in this population. Complex interactions between genetics, environment, and physiologic susceptibility are thought to contribute to disease. Management is primarily supportive in nature, though there are several approved treatments worldwide. This review details the mechanisms and evidence of approved disease-modifying treatments, relevant measures to track disease burden and progression used in clinical trials, and approaches to pharmacologic management of common symptoms in ALS. As there is not currently a cure for ALS, research into the complex pathophysiologic and genetic alterations contributing to disease is of great interest. This review further discusses the current understanding of genetic etiologies and altered physiology leading to disease, such as neuroinflammation, integrated stress response, aberrant proteostasis and mitochondrial dysfunction, among others. The translation of preclinical discoveries into current investigational therapeutics, novel therapeutic categories such as antisense oligonucleotides and stem cell transplantation, as well as future horizons harnessing the power of artificial intelligence in drug development and clinical trials are discussed.},
}

@article {pmid40897843,
year = {2025},
author = {Lai, Q and Zhang, X and Jiang, S and Krzyaniak, MD and Alayoglu, S and Agarwal, A and Liu, Y and Edenfield, WC and Kobayashi, T and Wang, Y and Dravid, V and Wasielewski, MR and Miller, JT and Kratish, Y and Marks, TJ},
title = {Stable single-site organonickel catalyst preferentially hydrogenolyses branched polyolefin C-C bonds.},
journal = {Nature chemistry},
volume = {},
number = {},
pages = {},
pmid = {40897843},
issn = {1755-4349},
support = {DOE DE-SC0024448//U.S. Department of Energy (DOE)/ ; DE-FG02-99ER14999//U.S. Department of Energy (DOE)/ ; DE-SC0001329//U.S. Department of Energy (DOE)/ ; DE-FG02-99ER14999//U.S. Department of Energy (DOE)/ ; DE-SC0012704//U.S. Department of Energy (DOE)/ ; NSF ECCS-2025633//National Science Foundation (NSF)/ ; NNA04CC36G//NASA | Ames Research Center/ ; },
abstract = {Current methods of processing accumulated polyolefin waste typically require harsh conditions, precious metals or high metal loadings to achieve appreciable activities. Here we examined supported, single-site organonickel catalysts for polyolefin upcycling. Chemisorption of Ni(COD)2 (COD, 1,5-cyclooctadiene) onto Brønsted acidic sulfated alumina (AlS) yields a highly electrophilic Ni(I) precatalyst, AlS/Ni(COD)2, which is converted under H2 to the active AlS/Ni[II]H catalyst. This single-site system exhibits unique hydrogenolysis selectivity that favours cleaving branched polyolefin C-C linkages, enabling the hydrogenolytic separation of polyethylene and isotactic polypropylene (iPP) mixtures. Moreover, AlS/Ni[II]H remains highly selective and active for hydrogenolysis of iPP admixed with polyvinyl chloride, and the spent catalyst can be repeatedly regenerated by AlEt3 treatment. Experimental mechanistic analysis and density functional theory modelling reveal a turnover-limiting C-C scission pathway featuring β-alkyl transfer and strong olefin binding. These results highlight the potential of nickel-based systems for the selective upcycling of complex plastic waste streams.},
}

@article {pmid40896928,
year = {2025},
author = {Issa, NP and Aydin, S and Goicoechea, EB and Carberry, N and Garret, MA and Smith, S and Habib, AA and Soliven, B and Rezania, K},
title = {Intermuscular coherence from muscle pairs in the leg as a biomarker for amyotrophic lateral sclerosis.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {179},
number = {},
pages = {2110986},
doi = {10.1016/j.clinph.2025.2110986},
pmid = {40896928},
issn = {1872-8952},
abstract = {OBJECTIVE: To evaluate the diagnostic potential of intermuscular coherence (IMC) measured from leg muscle pairs as an early-stage biomarker for amyotrophic lateral sclerosis (ALS).

METHODS: Surface electromyography (sEMG) was recorded in neurotypical subjects and patients with early-stage ALS from muscle pairs: gastrocnemius lateralis-gastrocnemius medialis (GLGM), tibialis anterior-extensor digitorum brevis (TAED), and vastus lateralis-vastus medialis (VLVM). IMC within the 20-40 Hz range (IMCβγ) and the imaginary component of coherency in the 20-40 Hz range (ICOHβγ) were calculated. Area under the receiver operating characteristic curves (AUC) was used to assess diagnostic performance.

RESULTS: IMCβγ was lower in ALS patients than neurotypical subjects for all three muscle pairs (p < 0.05 in all cases). Diagnostic performance (AUC) ranged from 0.69 to 0.78 and was highest for TAED. Reducing the effect of volume conduction by using ICOHβγ tended to improve the diagnostic ability (AUC range 0.76 to 0.84).

CONCLUSIONS: IMCβγ from leg muscles, particularly TAED, can help differentiate early-stage ALS patients from neurotypical individuals. ICOHβγ further improves diagnostic performance by reducing volume conduction artifacts.

SIGNIFICANCE: Leg muscle IMC measurements could aid in the early and accurate diagnosis of ALS.},
}

@article {pmid40896593,
year = {2025},
author = {Ueno, Y and Nakamura, Y and Hata, T},
title = {The potential role of microRNA-mediated motor neuron-muscle pathologic interactions in amyotrophic lateral sclerosis.},
journal = {Molecular therapy. Nucleic acids},
volume = {36},
number = {3},
pages = {102675},
pmid = {40896593},
issn = {2162-2531},
}

@article {pmid40895800,
year = {2025},
author = {D'Arrigo, C and Labbate, S and Galante, D},
title = {Boosting the Therapeutic Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells via Advanced Preconditioning for Neurodegenerative Disorders.},
journal = {Stem cells international},
volume = {2025},
number = {},
pages = {2616653},
doi = {10.1155/sci/2616653},
pmid = {40895800},
issn = {1687-966X},
abstract = {Acute and chronic neurodegenerative conditions (NDs) are major causes of disability and mortality worldwide. Acute NDs encompass conditions such as stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). On the other hand, chronic NDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Currently, no definitive cure exists for these diseases, and available therapies focus primarily on slowing the progression of symptoms. Mesenchymal stem cells (MSCs), due to their multilineage differentiation capacity, immunomodulatory abilities, and regenerative properties, have gained attention in regenerative medicine. In recent years, extracellular vesicles (EVs) derived from MSCs have shown great promise as a cell-free therapeutic approach, eliminating the risks associated with direct MSCs use, such as tumorigenicity and poor cell survival after transplantation. EVs have emerged as powerful mediators of intercellular communication and tissue repair, exhibiting immunomodulatory, anti-inflammatory, and proregenerative properties. However, limitations such as low EVs yield and reduced efficacy due to MSCs replicative senescence restrict their therapeutic potential. Preconditioning strategies, including hypoxia, 3D cultures, and biochemical priming, have been explored in other fields to enhance EVs properties, yet their specific application to NDs remains under-reported. This review aims to address this gap by analyzing the preconditioning methods used to boost the therapeutic potential of MSCs-derived EVs for neurodegenerative diseases. These preconditioning strategies may enhance EVs yield, functional cargo, and targeted therapeutic efficacy for treating acute and chronic NDs.},
}

@article {pmid40895324,
year = {2025},
author = {Tan, X and Liu, G and Li, X and Zhong, F and Su, Z and Wang, H},
title = {Amyotrophic Lateral Sclerosis and Risk of Common Cancer: Mendelian Randomization Interrogation of Causality and Mediation.},
journal = {Phenomics (Cham, Switzerland)},
volume = {5},
number = {3},
pages = {270-283},
doi = {10.1007/s43657-024-00159-9},
pmid = {40895324},
issn = {2730-5848},
abstract = {UNLABELLED: Compared with the well-documented inverse comorbidity of common neurodegenerative diseases with some types of cancer, the association of amyotrophic lateral sclerosis (ALS) with cancer was obscure. This Mendelian randomization (MR) analysis was aimed to appraise the causal relationship of ALS with cancer. Leveraging summary statistics of genome-wide association study (GWAS) for ALS, overall-cancer and nine types of site-specific common solid cancer including colorectal cancer (CRC) in populations of European (discovery and replication) and East Asian ancestry, we investigated the causal association of ALS with cancer using inverse-variance weighted (IVW) method and complementary sensitivity analyses. We performed MR-based mediation analysis to assess possible role of serum lipid traits such as hyperlipidemia, one shared risk factor of ALS and CRC, in their causal association. We found that genetically-predicted ALS was not associated with overall-cancer and other tested types of cancer, but was causally associated with reduced risk of CRC [odds ratio (OR) 0.84; 95% confidence interval (95% CI) 0.74-0.96; p = 0.011, OR 0.32; 95% CI 0.15-0.69; p = 0.004, in datasets of European (discovery) and East Asian ancestry respectively]. We observed absences of directional pleiotropy (MR Egger, intercept = -0.02 and -0.02, p = 0.49 and 0.60), instrumental outlier (MR-PRESSO, p = 0.95 and 0.84) or heterogeneity (Cochran Q, p = 0.95 and 0.82). Null reverse causality of CRC with ALS was found in either datasets. However, we found no evidence of the inverse association of ALS with CRC in either the replication (OR 0.99; 95% CI 0.93-1.06) or the combined European datasets (OR 0.92; 95% CI 0.79-1.09). Mediation analysis in European datasets suggested that hyperlipidemia may affect the risk of CRC via ALS in an indirect manner, with the measured mediation effect of hyperlipidemia on CRC being -0.02 (95% CI -0.04 to -0.002, p = 0.03). Our two-sample MR study in trans-ethnic populations uncovered that genetically proxied ALS may be causally associated with reduced risk of CRC, providing new insight into the inverse comorbidity and etiological causality of neurodegenerative disease and cancer.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-024-00159-9.},
}

@article {pmid40894870,
year = {2025},
author = {Manville, RW and Sidlow, R and Abbott, GW},
title = {Conifer metabolite pisiferic acid restores activity in human Kv1.2 potassium channels carrying pathogenic sequence variants.},
journal = {iScience},
volume = {28},
number = {9},
pages = {113283},
doi = {10.1016/j.isci.2025.113283},
pmid = {40894870},
issn = {2589-0042},
abstract = {Sequence variants in KCNA2, the gene encoding voltage-gated potassium channel Kv1.2, cause epilepsy, delayed cognitive development, and movement disorders. Drugs that directly correct mutant Kv1.2 function are lacking. Kv1.2 downregulation is also implicated in pain and amyotrophic lateral sclerosis (ALS). We recently found that the abietane diterpenoid pisiferic acid (PA) from conifer Chamaecyparis pisifera beneficially restores activity in pathogenic loss-of-function (LOF)-variant Kv1.1 channels. Here, using cellular electrophysiology, we classified 19 human Kv1.2 gene variants (pathogenic or of unknown significance) into LOF, gain of function (GOF), or mixed LOF/GOF. By hyperpolarizing their voltage dependence of activation, PA improved function in 13/13 LOF and 1/1 LOF/GOF pathogenic Kv1.2 variants tested, using cRNA ratios representative of autosomal dominant KCNA2 disorders. In silico docking, mutagenesis, and electrophysiology identified a PA binding site in the Kv1.2 voltage sensor. Given its in vitro efficacy and low preclinical toxicity, PA is a promising lead compound for Kv1.2 LOF disorders.},
}

@article {pmid40894255,
year = {2025},
author = {Hu, N and Chen, L and Hu, G and Ma, R},
title = {Advancements in extracellular vesicle therapy for neurodegenerative diseases.},
journal = {Exploration of neuroprotective therapy},
volume = {5},
number = {},
pages = {},
doi = {10.37349/ent.2025.1004104},
pmid = {40894255},
issn = {2769-6510},
abstract = {Neurodegenerative diseases represent a significant and growing challenge to public health worldwide. Current therapeutic strategies often fall short in halting or reversing disease progression, highlighting the urgent need for novel approaches. Extracellular vesicles (EVs) have garnered attention as potential therapeutic agents due to their role in intercellular communication and their ability to transport bioactive cargo, including proteins, nucleic acids, and lipids. This review provides a comprehensive overview of the biology of EVs, their involvement in neurodegenerative diseases, and the potential for EV-based therapies. We discuss the different types of EVs, their biogenesis, and their cargo composition, emphasizing their relevance to neurological processes such as protein misfolding, neuroinflammation, and oxidative stress. Preclinical studies investigating EVs as carriers of therapeutic cargo and their ability to promote neuronal survival and regeneration are examined, with a focus on evidence from animal models of neurodegenerative disorders. We explore the use of EVs in the treatment of neurodegenerative diseases, including ongoing clinical trials, methods for EV isolation and modification, and future perspectives on personalized EV-based therapies designed to meet the unique needs of individual patients. Overall, this review highlights the potential of EVs as a promising avenue for neurodegenerative disease therapy, while also addressing key research gaps and translational hurdles that need to be overcome for their successful clinical implementation.},
}

@article {pmid40892373,
year = {2025},
author = {Dietrich, J and Hollstein, A},
title = {Authors' response to Tiffet et al.'s comment on "Performance and Reproducibility of Large Language Models in Named Entity Recognition: Considerations for the Use in Controlled Environments".},
journal = {Drug safety},
volume = {},
number = {},
pages = {},
pmid = {40892373},
issn = {1179-1942},
}

@article {pmid40891814,
year = {2025},
author = {Ekaterina Slotina, DM and Ditscheid, DRNB and Meissner, DPF and Wiese, A and Hezel, J and Marschall Dipl Oec, DMU and Wedding, APDMU and Freytag, PDRPMA},
title = {Quality of Palliative Care in Nursing Homes and Community Care in Deceased with Chronic Obstructive Pulmonary Disease (COPD), Dementia, Amyotrophic Lateral Sclerosis (ALS), and Cancer: A Retrospective Analysis of Claims Data (2016-2019).},
journal = {Journal of palliative care},
volume = {},
number = {},
pages = {8258597251353315},
doi = {10.1177/08258597251353315},
pmid = {40891814},
issn = {2369-5293},
abstract = {ObjectivePalliative care is more commonly provided to patients with cancer than to those with non-oncological conditions. Little is known about the prevalence of inappropriate care and whether differences exist depending on the underlying disease. This study investigates the care during the last month of life in patients with cancer and non-oncological conditions, such as amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), and dementia, considering the care setting (nursing home vs. community care).MethodsWe conducted a population-based, retrospective analysis of deceased in 2016-2019 with COPD (n = 4,036), dementia (n = 40,853), or ALS (n = 608). Logistic regression analyses compared the care quality with that of the deceased with cancer (n = 58,315). Interaction analyses examined setting effects. Outcome measures included validated quality indicators: hospital and intensive care unit (ICU) stays, emergency service utilization, and place of death.ResultsDeceased with COPD, dementia, and ALS more frequently utilized emergency services compared to those with cancer (40.4%, 28.4%, 29.0% vs. 24.4%, respectively, p < .05) and were less likely to die in a hospital (excluding palliative care units; 38.2%, 15.3%, 25.7% vs. 40.3%, respectively, p < .05). Differences were observed in ICU (13.6%, 3.4%, 6.1% vs. 4.3%, respectively, p < .05) and hospital admissions (42.7% for COPD vs. 31.5% for oncological patients, p < .001). The same pattern was observed across all conditions: deceased in community care had higher rates in all quality indicators than those in nursing homes.ConclusionsThe results suggest differences in care quality depending on the underlying disease. Nononcological patients in community care are less frequently and less adequately cared for than oncological patients.},
}

@article {pmid40891578,
year = {2025},
author = {Toyota, S},
title = {Expanding Chemistry of Expanded Helicenes.},
journal = {Chemistry (Weinheim an der Bergstrasse, Germany)},
volume = {},
number = {},
pages = {e02193},
doi = {10.1002/chem.202502193},
pmid = {40891578},
issn = {1521-3765},
support = {23K26637//Japan Society for the Promotion of Science/ ; 20H02721//Japan Society for the Promotion of Science/ ; 23H01944//Japan Society for the Promotion of Science/ ; },
abstract = {Expanded helicenes are interesting compounds created by modifying the original helicene structure through the incorporation of linearly fused benzene rings, enlarging the helical diameter. Motivated by Tilley et al.'s report of a key expanded helicene structure in 2017, several research groups have synthesized such nonplanar aromatic compounds, aiming to explore their impressive structures, properties, and chiroptical performance. This review highlights recent advances in the expanded helicene chemistry through experimental and theoretical studies. The shape and length of helical structures depend on the number and combination of angularly and linearly fused benzene rings. Helical structures are classified using notations, and specific compounds corresponding to each structural form, namely, hexagonal, triangular, rhombic, or others, are introduced herein. As an extension of the molecular design, examples of nonhexagonal and heteroaromatic ring-embedded expanded helicenes are presented. Specifically, this review focuses on how the diameters, lengths, and turn numbers of helical structures depend on dynamic processes involving helical inversion and chiroptical properties (circular dichroism (CD) and circularly polarized luminescence (CPL)). The characteristics and perspectives of this molecular design are also discussed.},
}

@article {pmid40891506,
year = {2025},
author = {Pir, GJ and Buddenkotte, J and Alam, MA and Own, A and Eck, RJ and Kraemer, BC and Mandelkow, E and Steinhoff, M},
title = {TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70239},
pmid = {40891506},
issn = {1742-4658},
support = {11S-0117 180326//Qatar National Research Fund/ ; //Katharina Hardt Foundation/ ; F99AG088436/NH/NIH HHS/United States ; //Cure Alzheimer's Fund/ ; },
abstract = {TDP-linked proteinopathies, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE), are characterised by pathogenic deposits containing transactive response DNA-binding protein 43 (TDP-43) in the brain and spinal cord of patients. These hallmark pathological features are associated with widespread neuronal dysfunction and progressive neurodegeneration. TDP-43's role as an essential RNA/DNA-binding protein in RNA metabolism and gene expression regulation is clear, but deciphering the intricate pathophysiological mechanisms underpinning TDP-43-mediated neurodegeneration is paramount for developing effective therapies and novel diagnostic tools for early detection before frank neuronal loss occurs. The nematode Caenorhabditis elegans, with highly conserved TDP-43 orthologue TDP-1, serves as a powerful genetic model to investigate the molecular underpinnings of TDP-43 proteinopathies. Here, we provide a brief overview of the structural and functional characteristics of TDP-43 and TDP-1, highlighting their conserved roles in RNA metabolism, stress responses, and neurodegeneration. We then delve into the pathobiology of TDP-43, drawing insights from C. elegans models expressing either monogenic TDP-43 variants or bigenic combinations with ALS-associated risk genes, and discuss how these models have advanced our understanding of the pathomechanisms of TDP-43 proteinopathies. By employing its simplicity and genetic manipulability, we discuss how these models have helped identify chemical and genetic suppressors of TDP-43-induced phenotypes, including small molecules like Pimozide and the probiotic Lacticaseibacillus rhamnosus HA-114, now in clinical trials. This review underscores the translational value of C. elegans in unraveling the biochemical pathways and interactions in TDP-43 proteinopathies that perturb cellular physiology, potentially facilitating mechanism-based therapy development.},
}

@article {pmid40891053,
year = {2025},
author = {Bilican, S and Nabawi, Y and Zhang, WH and Petrovic, D and Wehrmann, M and Muñoz-García, S and Koyuncu, S and Vilchez, D},
title = {C9orf72 ALS-causing mutations lead to mislocalization and aggregation of nucleoporin Nup107 into stress granules.},
journal = {FEBS letters},
volume = {},
number = {},
pages = {},
doi = {10.1002/1873-3468.70156},
pmid = {40891053},
issn = {1873-3468},
support = {CRC1678 (project B06 to D.V)//Deutsche Forschungsgemeinschaft/ ; Germany's Excellence Strategy-CECAD (EXC2030-39390661388)//Deutsche Forschungsgemeinschaft/ ; Largeinstrument grant (INST216/1329-1 FUGG to CECAD Proteomics Facility)//Deutsche Forschungsgemeinschaft/ ; Research Unit FOR5762 (project VI742/10-1 to D.V)//Deutsche Forschungsgemeinschaft/ ; 2021-EKSE.95 to D.V//Else Kröner-Fresenius-Stiftung/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disorder caused by motor neuron degeneration. Hexanucleotide repeat expansions in the C9orf72 gene, the most common genetic cause of ALS (C9-ALS), drive toxicity through different mechanisms. These pathological changes include alterations in stress granules (SGs), ribonucleoprotein complexes formed under stress conditions. Here, we show that G3BP1, a core component of SGs, exhibits enhanced interaction with the nucleoporin Nup107 in motor neurons derived from patient iPSCs carrying C9orf72 mutations. Moreover, Nup107 colocalizes with SGs and aggregates in C9-ALS motor neurons. Notably, knockdown of npp-5, the Caenorhabditis elegans ortholog of Nup107, alleviates ALS-associated phenotypes in worm models, including reduced lifespan and impaired motility. Together, our findings provide insights into disease-related changes in C9-ALS pathogenesis.},
}

@article {pmid40891024,
year = {2025},
author = {Pan, Y and Spiteri, AG and Runwal, P and Sun, J and Hutchinson, DS and Kagawa, Y and Turner, BJ and Huang, C and Shah, AD and Schittenhelm, RB and Nicolazzo, JA},
title = {Increased ATP production and P-glycoprotein activity underlie the marked changes in blood-brain barrier transport of drugs in a mouse model of amyotrophic lateral sclerosis.},
journal = {British journal of pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bph.70147},
pmid = {40891024},
issn = {1476-5381},
support = {23AARF-1020292/ALZ/Alzheimer's Association/United States ; GNT2007912//National Health and Medical Research Council/ ; //FightMND/ ; },
abstract = {BACKGROUND AND PURPOSE: Patients with amyotrophic lateral sclerosis (ALS) are prescribed many medications for symptomatic relief. However, how potential alterations to the blood-brain barrier (BBB) affect the brain exposure of drugs in ALS remains under-investigated.

EXPERIMENTAL APPROACH: We used high-dimensional proteomic analysis, cellular metabolism, and mitochondrial functional assays to characterise isolated brain microvascular endothelial cells (BMECs) from wildtype and SOD1[G93A] transgenic mice, a mouse model of familial ALS, at a late-symptomatic age (P115-120), together with a transcardiac brain perfusion technique to assess BBB function in situ.

KEY RESULTS: The BBB of the SOD1[G93A] transgenic (TG) mice was significantly altered, including a 1.3-fold decrease in apparent brain microvascular volume, and decreased BBB transport of [3]H-diazepam (1.4-fold) and [3]H-2-deoxy-D-glucose (1.2-fold). BMEC proteomic analysis revealed multiple changes in TG mice including altered transmembrane activity, metabolism, and mitochondrial function, as revealed by gene set enrichment analysis, alongside altered glucose transporter (Glut1) abundance. These proteomic findings supported the identified increase in mitochondrial basal/ATP-linked respiration, mitochondrial action potential, ATP production, and intracellular ATP levels in SOD1[G93A] mouse BMECs. The BBB transport of [3]H-digoxin, a specific ATP-binding cassette efflux P-glycoprotein (P-gp) substrate, was reduced by 11.0% in SOD1[G93A] mice. This was confirmed by a 46.7% reduction in BMEC uptake of [3]H-digoxin, an observation that was reversed by resolving the hypermetabolic state of SOD1[G93A] BMECs.

CONCLUSION AND IMPLICATIONS: These findings open possible therapeutic avenues that could be exploited to overcome P-gp-mediated CNS drug resistance in ALS.},
}

@article {pmid40888144,
year = {2025},
author = {Hullock, K and O'Cathain, A and Sampson, F and Woodward, J and Coates, E and Stavroulakis, T and White, SM and White, D and Norman, P and McDermott, C},
title = {Optimising Calorie Intake for People With Amyotrophic Lateral Sclerosis: A Process Evaluation of a Complex Behaviour Change Intervention.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70417},
pmid = {40888144},
issn = {1369-7625},
support = {//This project is funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-1016-20006) and supported by the NIHR Sheffield Biomedical Research Centre./ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diet therapy/psychology ; Female ; Male ; *Energy Intake ; United Kingdom ; Middle Aged ; Aged ; Caregivers/psychology ; Process Assessment, Health Care ; Qualitative Research ; Adult ; },
abstract = {OBJECTIVE: To explore intervention fidelity and experiences of using a new intervention designed to optimise calorie intake in people with amyotrophic lateral sclerosis (ALS).

METHODS: A mixed-methods process evaluation was conducted alongside an ongoing randomised controlled trial across 15 ALS specialist centres in the United Kingdom. Data collection included 146 healthcare professional-completed fidelity checklists, audio recordings of 5 intervention sessions, and qualitative interviews with 32 healthcare professionals, patients and informal caregivers.

RESULTS: Intervention fidelity was high (88%: 1059/1204 items completed by healthcare professionals). Healthcare professionals, patients and informal caregivers within the sample recognised the intervention's value and engaged with it. Patients were motivated to use the intervention because they believed it could slow disease progression, and it gave them a sense of control. Despite challenges with the intervention, including patient concerns about weight gain and physical limitations in food preparation and consumption, patients in this sample remained committed to using the intervention. However, healthcare professionals suggested that these challenges may have negatively influenced trial recruitment and retention. Caregivers played a crucial role in supporting patients emotionally and physically, helping them to adhere to the intervention.

CONCLUSIONS: The intervention was feasible to implement and was delivered with fidelity. While patient engagement in this sample was strong, the intervention usability may be time-limited as physical function declines. Therefore, the intervention may be best suited for those with slower-progressing ALS who can manage the intervention and dietary changes. Moving forward, continued evaluation is needed to assess effectiveness and explore subgroup differences based on ALS type (slow vs. fast progressing).

PPIE CONTRIBUTION: PPI was integral to the process evaluation. PPI members reviewed key study documents, including the Participant Information Sheet and consent forms, leading to participant materials that were clear and easily understood. They also participated in developing the intervention.

TRIAL REGISTRATION: IRAS ID 275949, ISRCTN30588041.},
}

Humans
*Amyotrophic Lateral Sclerosis/diet therapy/psychology
Female
Male
*Energy Intake
United Kingdom
Middle Aged
Aged
Caregivers/psychology
Process Assessment, Health Care
Qualitative Research
Adult

@article {pmid40888932,
year = {2025},
author = {Platikanov, S and Palomas, A and Mata, MC and Tauler, R and Villar, J and Bragós, R and Bermejo, S and Jaumot, J and Lacorte, S},
title = {Coupling electrochemical and spectroscopic methods for river water dissolved organic matter characterization.},
journal = {Environmental monitoring and assessment},
volume = {197},
number = {9},
pages = {1071},
pmid = {40888932},
issn = {1573-2959},
support = {TED2021-131552B-C21 and TED2021-131552B-C22//Ministerio de Ciencia e Innovación (MCIN) y la Agencia Estatal de Investigación (AEI) and the European Union 'Next Generation EU/PRTR/ ; },
mesh = {*Rivers/chemistry ; *Environmental Monitoring/methods ; *Water Pollutants, Chemical/analysis ; Electrochemical Techniques ; Spectrometry, Fluorescence ; Spectrum Analysis ; *Humic Substances/analysis ; Dielectric Spectroscopy ; },
abstract = {Monitoring dissolved organic matter (DOM) in surface waters is essential for assessing ecosystem health and detecting pollution. However, conventional spectroscopic techniques often provide limited information about the electrochemical behavior of DOM. This study integrates electrochemical impedance spectroscopy (EIS) with classical methods such as UV-Vis absorption and fluorescence spectroscopies to improve DOM characterization in river water samples. In particular, this coupling provides additional insights into the electrochemical properties of DOM, which are not captured by conventional spectroscopic techniques. This study combined multiple data sources, including physicochemical parameters (e.g., water temperature, pH, conductivity), EIS spectral scores, fluorescence indices, and DOM fractions resolved by multivariate curve resolution-alternating least squares (MCR-ALS) applied to excitation-emission matrix (EEM) fluorescence data. The results from these different methods were then merged into a single dataset for a global principal component analysis (PCA), which allowed us to identify shared patterns and correlations across methods. The results revealed that low-altitude rivers showed the highest DOM content, followed by mid-altitude rivers, while high-altitude rivers presented the lowest. The PCA model indicated that low-frequency regions in the EIS spectra correlated with higher DOM content, whereas mid- to high-frequency regions were associated with lower DOM levels. These frequency-dependent patterns reflected differences in charge transfer and dielectric behavior of DOM in the river samples, which are not accessible through optical techniques. This highlights the potential of EIS as a complementary tool that provides electrochemical information on DOM composition for better water quality assessment.},
}

*Rivers/chemistry
*Environmental Monitoring/methods
*Water Pollutants, Chemical/analysis
Electrochemical Techniques
Spectrometry, Fluorescence
Spectrum Analysis
*Humic Substances/analysis
Dielectric Spectroscopy

@article {pmid40888599,
year = {2025},
author = {Mearelli, M and Hirschberg, I and Weissleder, C and Giachino, C and Pérez, MJ and Dubroux, M and Provenzano, F and Rizzuti, M and Ottoboni, L and Sheth, U and Gendron, TF and Corti, S and Deleidi, M},
title = {C9orf72 Repeat Expansion Induces Metabolic Dysfunction in Human iPSC-Derived Microglia and Modulates Glial-Neuronal Crosstalk.},
journal = {Glia},
volume = {},
number = {},
pages = {},
doi = {10.1002/glia.70080},
pmid = {40888599},
issn = {1098-1136},
support = {01GM1913//E-Rare3 INTEGRALS/ ; 101003329/ERC_/European Research Council/International ; 490761034//Deutsche Forschungsgemeinschaft/ ; 01ED2005B//EU Joint Programme - Neurodegenerative Disease Research/ ; },
abstract = {The C9orf72 hexanucleotide repeat expansion mutation is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but its cell type-specific effects on energy metabolism and immune pathways remain poorly understood. Using induced pluripotent stem cell (iPSC)-derived motor neurons, astrocytes, and microglia from C9orf72 patients and their isogenic controls, we investigated metabolic changes at the single-cell level under basal and inflammatory conditions. Our results showed that microglia are particularly susceptible to metabolic disturbances. While C9orf72 motor neurons exhibited impaired mitochondrial respiration and reduced ATP production, C9orf72 microglia presented pronounced increases in glycolytic activity and oxidative stress, accompanied by the upregulation of the expression of key metabolic enzymes. These metabolic changes in microglia were exacerbated by inflammatory stimuli. To investigate how these changes affect the broader cellular environment, we developed a human iPSC-derived triculture system comprising motor neurons, astrocytes, and microglia. This model revealed increased metabolic activity in all cell types and highlighted that microglia-driven metabolic reprogramming in astrocytes contributes to the vulnerability of motor neurons under inflammatory conditions. Our findings highlight the central role of microglia in driving metabolic dysregulation and intercellular crosstalk in ALS pathogenesis and suggest that targeting metabolic pathways in immune cells may provide new therapeutic avenues.},
}

@article {pmid40887399,
year = {2025},
author = {Wang, Y and Lin, J and Qu, Y and Ding, Y and Ye, Z and Zhu, Z and Chen, W and Chen, Z and Sun, H and Hu, F and Chen, C and Fang, L and Li, R and Zhang, B and Wang, N and Fu, Y and Chen, W and Zhang, Q and , },
title = {Corrigendum to "Biomarker profile of a Chinese ALS cohort: A comprehensive clinical-biomarkers-imaging analysis".},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107073},
doi = {10.1016/j.nbd.2025.107073},
pmid = {40887399},
issn = {1095-953X},
}

@article {pmid40887165,
year = {2025},
author = {Eising, J and Dissmeyer, N},
title = {Identification of arginylated N-termini with specific reagents.},
journal = {Methods in enzymology},
volume = {718},
number = {},
pages = {307-317},
doi = {10.1016/bs.mie.2025.06.024},
pmid = {40887165},
issn = {1557-7988},
mesh = {Humans ; *Protein Processing, Post-Translational ; *Arginine/metabolism/chemistry ; *Aminoacyltransferases/metabolism ; *Proteins/metabolism/chemistry ; Animals ; },
abstract = {N-terminal arginylation is a posttranslational modification of proteins that may determine their fate with respect to their stability and half-life and timing of their physiological and molecular function. Arginylated N-termini are in some documented cases N-degrons leading to degradation through the proteasome or autophagic-lysosomal system (ALS) regulating cellular homeostasis and global physiological alterations. Proteins that are targets of arginyl-transferases (Ates) capable of ligating arginine (Arg) residues to N-terminal amino groups and internal side chains show therefore high importance for manipulation in therapeutic and research contexts. Because of that, identifying those substrates is of high interest for all organisms from human to plant research. This chapter will shed some light onto methods for identification of arginylated N-termini with focus on specific antibodies targeting the N-terminally modified proteins.},
}

Humans
*Protein Processing, Post-Translational
*Arginine/metabolism/chemistry
*Aminoacyltransferases/metabolism
*Proteins/metabolism/chemistry
Animals

@article {pmid40887101,
year = {2025},
author = {Guillot, SJ and Luppi, PH and Dupuis, L and Bolborea, M},
title = {Sleep in neurodegenerative diseases: A focus on melatonin, melanin-concentrating hormone and orexin.},
journal = {Journal of neuroendocrinology},
volume = {},
number = {},
pages = {e70085},
doi = {10.1111/jne.70085},
pmid = {40887101},
issn = {1365-2826},
support = {ANR-16-CE16-0015//Agence Nationale de la Recherche/ ; ANR-16-CE92-0031//Agence Nationale de la Recherche/ ; ANR-19-CE17-0016//Agence Nationale de la Recherche/ ; ANR-20-CE17-0008//Agence Nationale de la Recherche/ ; ANR-24-CE37-4064//Agence Nationale de la Recherche/ ; //TargetALS/ ; //Fondation Thierry Latran/ ; //Association Francaise de Recherche sur la sclérose latérale amyotrophique/ ; //Radala Foundation for ALS Research/ ; //ARSLA/ ; //University of Starsbourg fundation/ ; //Fondation Bettencourt Schueller/ ; DEQ20180339179//Fondation pour la Recherche Médicale/ ; //Axa Research Funds/ ; },
abstract = {Sleep and circadian rest-activity rhythm alterations are recognised as inherent clinical features of various neurodegenerative diseases. Traditionally viewed as secondary manifestations of neurodegeneration, recent studies have revealed that disruptions in circadian rhythm and sleep-wake cycles can precede clinical symptoms and significantly contribute to the underlying pathophysiological progression. In this review, we summarise recent research on the impact of sleep and circadian rhythm alterations in ageing and major neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and frontotemporal dementia, highlighting the roles of melatonin, orexin, and melanin-concentrating hormone (MCH) systems as key regulators at the intersection of sleep and neurodegeneration. We argue that sleep and circadian alterations may serve as early biomarkers and therapeutic targets for these diseases.},
}

@article {pmid40886845,
year = {2025},
author = {Beraja, GE and Eber, AE and Yosipovitch, G},
title = {Response to Peng et al.'s "Efficacy and safety of 308-nanometer light-emitting diode phototherapy for Prurigo Nodularis: A randomized and self-controlled clinical trial.".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.08.064},
pmid = {40886845},
issn = {1097-6787},
}

@article {pmid40885478,
year = {2025},
author = {Hafiz, B and Aldahlawi, A and Ashqar, A and Hamzah, A and Alotaibi, Y and Bajunaid, K and Baeesa, S},
title = {Outcomes of Surgical Versus Endovascular Treatment of Spinal Dural Arteriovenous Fistula: A Systematic Review and Meta-Analysis.},
journal = {World neurosurgery},
volume = {},
number = {},
pages = {124420},
doi = {10.1016/j.wneu.2025.124420},
pmid = {40885478},
issn = {1878-8769},
abstract = {BACKGROUND: Spinal dural arteriovenous fistulas (SDAVFs) are the most prevalent type of spinal vascular malformation and can lead to progressive neurological impairments if left untreated. Endovascular embolization and microsurgical resection are treatment options, although the optimal treatment method remains a subject of debate.

OBJECTIVE: A comprehensive systematic review and meta-analysis to compare the endovascular and microsurgical treatment outcomes of SDAVFs.

METHODS: An exhaustive literature search was conducted in the PubMed, Embase, Scopus, and Web of Science databases, encompassing publications from 2014 to 2024. A total of 522 patients from seven studies (417 surgical and 105 endovascular) met the inclusion criteria. Information on post-treatment complications, recurrence/failure rates, and functional improvement as assessed by the Aminoff-Logue Scale (ALS) or modified ALS (mALS) was extracted. I[2] statistics were used to evaluate heterogeneity, and random-effects models were used to compute risk ratios (RRs) and odds ratios (ORs).

RESULTS: Compared to endovascular intervention, surgical treatment was linked to significantly lower rates of recurrence or treatment failure (RR: 0.19; 95% CI: 0.09-0.39; p < 0.001), especially in long-term follow-up and thoracic-level studies. With greater ALS/mALS gains and a higher percentage of patients achieving full or partial recovery, functional improvement favored surgery. Although complication types varied, complication rates were similar across modalities (OR: 0.84; 95% CI: 0.48-1.49). Asymmetry in funnel plots indicated possible publication bias in favor of successful surgical outcomes.

CONCLUSION: For SDAVFs, surgical ligation provides better long-term results than endovascular embolization in terms of neurological recovery and recurrence prevention. Even though both procedures are usually safe, surgery is the recommended first-line course of action due to the higher failure and recurrence rates linked to embolization, especially in patients with operable anatomy and progressive symptoms.},
}

@article {pmid40885336,
year = {2025},
author = {Pavlović, MD},
title = {Response to Li et al.'s "Therapeutic efficacy of platelet-rich plasma combining with microneedling and topical minoxidil in refractory severe androgenic alopecia["].},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.05.1463},
pmid = {40885336},
issn = {1097-6787},
}

@article {pmid40884740,
year = {2025},
author = {Kalasa Anil Kumar, AP and Subair, S and Basthikoppa Shivamurthy, P and Ummar, S and Rajeev, AC and Raju, R},
title = {Decoding ATXN2 Phosphocode: Structural Insights and Therapeutic Opportunities in Disease.},
journal = {The protein journal},
volume = {},
number = {},
pages = {},
pmid = {40884740},
issn = {1875-8355},
abstract = {Ataxin-2 (ATXN2), a key RNA-binding protein, regulates RNA metabolism, stress granule formation, and neuronal homeostasis, with dysregulated phosphorylation contributing to Spinocerebellar Ataxia type 2 (SCA2), amyotrophic lateral sclerosis (ALS), and cancer. This review integrates structural biology, phosphoproteomics, and interactome analyses to map six critical phosphosites (S772, T741, S624, S684, S784, S889) within ATXN2's intrinsically disordered regions. Modulated by kinases GSK3β and CDK13 and phosphatases like INPP5F, these sites orchestrate interactions with RNA-binding partners (e.g., ATXN2L, FXR2, STAU2) and co-regulated proteins (e.g., TP53BP1, NUP153), driving pathogenesis through disrupted autophagy, nucleocytoplasmic transport, and stress granule dynamics. We propose targeted therapies, including GSK3β inhibitors for ALS, antisense oligonucleotides for SCA2, and MTOR modulators for cancer, to restore ATXN2 function. By elucidating phosphocode of ATXN2, this work highlights novel avenues for precision medicine in neurodegenerative and oncogenic diseases.},
}

@article {pmid40884702,
year = {2025},
author = {Hu, X and Wei, M and Zhang, H and Wang, M and Zhang, S and Li, B},
title = {Characteristics and influencing factors of pain in amyotrophic lateral sclerosis: a focus on symptom management.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {},
number = {},
pages = {},
pmid = {40884702},
issn = {1590-3478},
abstract = {PURPOSE: To investigate the characteristics and influencing factors of pain symptoms in ALS patients, provide references for the formulation of pain coping measures in clinical practice.

MATERIALS AND METHODS: The research design was a cross-sectional study.ALS patients were investigated using scales such as the Brief Pain Inventory (BPI). Binary logistic regression equation and multiple linear regression equation were used to analyze the influencing factors of whether occur pain and pain degree in ALS patients.

RESULTS: 149 (74.1%) patients had pain symptoms, and 51 (25.4%) patients had pain as the first symptom. Patients with moderate to severe pain accounted for 60.4%. Fatigue, social support, self-efficacy, and poor sleep quality have been associated with whether occur pain in ALS patients. Personality traits, education, fatigue, social support, physical function, and self-efficacy were associated with pain levels in ALS patients.

CONCLUSIONS: Pain is an important indicator of functional decline, which can directly affect the rehabilitation outcome, reduce the quality of life of patients, and is crucial for predicting disease progression and optimizing end-of-life care, which should arouse the full attention of clinical medical personnel and scientific researchers. In the future, it is necessary to strengthen pain intervention in rehabilitation programs.},
}

@article {pmid40884436,
year = {2025},
author = {Berry, JD and Bowser, R},
title = {Cardiac Troponin T in Tofersen-Treated SOD1 ALS Patients: Beginning to Resolve the Catch-22 of Identifying Treatment Responsive Biomarkers in ALS Drug Development.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70017},
pmid = {40884436},
issn = {1097-4598},
}

@article {pmid40884086,
year = {2025},
author = {Khamkar, AS and Jha, S and Bakhla, AK and Chauhan, G},
title = {Large-scale genetic study identifies shared genetic regions between cerebrovascular and neurodegenerative diseases.},
journal = {International journal of stroke : official journal of the International Stroke Society},
volume = {},
number = {},
pages = {17474930251377513},
doi = {10.1177/17474930251377513},
pmid = {40884086},
issn = {1747-4949},
abstract = {IntroductionCerebrovascular diseases (CeVD) and neurodegenerative diseases (ND) are two major neurological disorders, which are associated with increasing global morbidity and mortality. Population-based studies have indicated a complex link between CeVD and ND. However, the shared genetic etiology between these disease conditions remains less explored.MethodsWe conducted genome-wide genetic correlation analysis and investigated the shared genetic architecture through pleiotropy analysis between ND and CeVD, like stroke and its subtypes, to understand shared genetic factors and biological mechanisms. Publicly available large-scale genome-wide association studies (GWAS) summary statistics data of cross-ancestry, European and South Asian (SAS) ancestry were analyzed using methods implemented in the tools LDSC, PLACO, and COLOC.ResultsWe detected 116 shared genetic loci consisting of 770 lead pleiotropic SNPs (ND-CeVD P-range: 4.81×10-8 to 4.57×10-16) and 40 shared causal genetic regions (ND-CeVD PP.H4-range: 0.70-0.9, posterior probability of H4 (PP.H4) ≥ 0.7) between multiple CeVD and ND pairs. The genetic regions near ICA1L, HLA-DQA1, HLA-DRB1, MIR297, and PITX2 genes were identified as highly pleiotropic across multiple CeVD-ND pairs. We report ERGIC1 (5q35.1) for the first time as a shared causal genetic locus between Amyotrophic Lateral Sclerosis and small vessel stroke. The genetic risk score of stroke derived from the SAS population of the GIGASTROKE study was associated with ND (P-range=2.23×10-28 to 0.02), despite a small sample size compared to other ethnic groups, indicating high penetrance.ConclusionThe shared genetic loci and pathway analysis in this study provides new genes and pathways shared between ND and CeVD, which may help in a better understanding of disease mechanisms in these neurological diseases.},
}

@article {pmid40883656,
year = {2025},
author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P},
title = {Geographic distribution of amyotrophic lateral sclerosis-related genes: a systematic review.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/17582024.2025.2554382},
pmid = {40883656},
issn = {1758-2032},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease. There is no effective treatment, but disease-modifying therapies do exist. Objective. To identify the geographical distribution of ALS-related genes.

METHODS: A systematic review was conducted according to the PRISMA 2020 guidelines in PubMed and Web of Science. Inclusion criteria: patients with ALS, no age or gender restriction, English and Spanish languages, studies published until 31 July 2025.

RESULTS: Thirty-eight results were obtained, 32 were selected, 19 articles were assessed for eligibility, and 8 articles were included from databases. Three articles recommended by clinical experts were added, so 11 results were reviewed. This research showed that published articles on the geographic distribution of ALS-related genes are limited, particularly for underrepresented regions such as Africa.

CONCLUSION: The findings demonstrate the need for intensified international research to improve knowledge of the genetic epidemiology of ALS.},
}

@article {pmid40883810,
year = {2025},
author = {Downs, J},
title = {A shift or a substitution? On naming, exclusion, and co-production in longstanding eating disorders: matters arising from Lubieniecki et al. (2025).},
journal = {Journal of eating disorders},
volume = {13},
number = {1},
pages = {196},
pmid = {40883810},
issn = {2050-2974},
abstract = {This Matters Arising piece responds to the article by Lubieniecki et al. (2025), which explores lived experience perspectives on the 'SEED' (Severe and Enduring Eating Disorder) classification. Written from the standpoint of someone with lived experience of a longstanding eating disorder and professional involvement in research, policy, and service development, the piece supports Lubieniecki et al.'s analysis of 'SEED' as both validating and restrictive. It extends their work by situating the classification within a broader landscape of psychiatric labelling associated with treatment exclusion. The limitations of replacing 'SEED' with alternative terminology alone are considered, with emphasis on the need for corresponding reforms to care pathways and their provision. The author highlights how diagnostic language can serve not only descriptive but also administrative and prognostic functions, often reflecting institutional constraints rather than individual need. The importance of co-produced approaches to diagnostic frameworks is also discussed, with emphasis on embedding lived experience throughout classificationand service design.},
}

@article {pmid40881903,
year = {2025},
author = {Shi, DD and Ding, J and Tian, J},
title = {Unraveling the enigma of salivary uric acid in periodontitis: Independent association, mechanistic insights, and future trajectories.},
journal = {World journal of clinical cases},
volume = {13},
number = {27},
pages = {108117},
doi = {10.12998/wjcc.v13.i27.108117},
pmid = {40881903},
issn = {2307-8960},
abstract = {This article explores the association between salivary uric acid (UA) and periodontitis, systematically analyzing its dual roles and research progress. Studies indicate that UA acts as a primary antioxidant in saliva under physiological conditions (accounting for 70%), protecting periodontal tissues by scavenging reactive oxygen species. However, when gum disease becomes severe, UA can switch roles and fuel inflammation, worsening tissue damage. Lorente et al's research found an independent inverse correlation between salivary UA levels and periodontitis severity (odds ratio = 6.14, P = 0.001), establishing 111 nmol/mL as a diagnostic threshold (area under the curve = 66%). Nevertheless, limitations include sample heterogeneity and failure to distinguish between gingivitis and periodontitis. Mechanistically, three hypotheses are proposed: The Antioxidant Depletion Hypothesis (UA oxidation consumption leading to feedback loops), the Microbial Metabolic Hijacking Hypothesis (pathogens utilizing UA as a carbon source to disrupt redox balance), and the Epithelial Barrier Dysfunction Hypothesis (UA deficiency causing downregulation of tight junction proteins). Future research should prioritize longitudinal cohorts to validate predictive value, integrate multi-omics to explore dysregulated signatures, and develop UA supplementation or targeted antioxidant therapies. This study provides novel insights into periodontitis diagnosis and mechanisms, advancing the application of salivary biomarkers in precision periodontics.},
}

@article {pmid40881744,
year = {2025},
author = {Zeppieri, M},
title = {Advantages and future outlooks in the use of telemedicine in liver transplantation.},
journal = {World journal of transplantation},
volume = {15},
number = {3},
pages = {104825},
doi = {10.5500/wjt.v15.i3.104825},
pmid = {40881744},
issn = {2220-3230},
abstract = {To maintain care during the coronavirus disease 2019 outbreak, telemedicine was implemented quickly. Jowell et al's pandemic study on telehealth integration and liver transplant evaluation is examined in this editorial. The study showed that telehealth did not affect clinical outcomes including time to evaluation, listing rates, or pre-transplant death. The study found that telehealth did not increase sociodemographic inequalities, suggesting a fair care framework. The editorial discusses how telemedicine in hepatology might help patients receive expert treatment while reducing logistical and financial burdens. Telehealth can democratize liver transplantation by delivering equivalent clinical results as in-person examinations. However, the editorial highlights technological barriers, difficulties in remotely assessing mental and physical health, and the need for specialized outreach to underserved communities. After the pandemic, telemedicine is essential to a more flexible, patient-centered healthcare system. The editorial encourages creativity and research to overcome challenges, improve hybrid care models, and ensure telehealth's egalitarian and successful potential. Pandemic insights can improve liver transplantation treatment and outcomes for diverse patient populations.},
}

@article {pmid40881531,
year = {2025},
author = {Chase, RC and Cortes, P and Lamb, CJ and Francis, D and DeVault, KR and Pang, M},
title = {Factors That Predict Endoscopic Evaluation and Gastrostomy Placement in Patients With Neurologic Disorders and Dysphagia.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88853},
doi = {10.7759/cureus.88853},
pmid = {40881531},
issn = {2168-8184},
abstract = {BACKGROUND: Although patients with neurologic disorders commonly develop dysphagia, there remains little consensus on the role of initial esophagogastroduodenoscopy (EGD) or temporal guidance on gastrostomy placement. We aimed to characterize the predictors associated with EGD and gastrostomy recommendation at the initial gastroenterology consultation in patients with progressive neurologic disorders.

METHODS: This retrospective study spanned from December 31, 2010, to December 31, 2021, and included patients with both dysphagia and neurologic disorders. Multivariate logistic regression determined the predictors for EGD and gastrostomy recommendation after the initial visit.

RESULTS: Out of 273 patients, EGD was recommended for 163 (59.7%) at the initial evaluation. A diagnosis of amyotrophic lateral sclerosis (ALS) (odds ratio: 0.20; 95% confidence interval (CI): 0.07-0.52; P=0.001) and being referred by a neurologist (odds ratio: 0.37; 95% CI: 0.17-0.84; P<0.02) were the negative predictors of an initial EGD recommendation. Gastrostomy was recommended for 38 patients (13.9%) at the initial consultation. Dysphagia to both liquids and solids, body mass index, diagnosis of ALS, and clinical frailty scale scores were associated with gastrostomy (P≤0.01). A model of six variables had high predictive accuracy for EGD recommendation (area under the receiver operating characteristic curve: 0.7741).

CONCLUSIONS: This study proposes a predictive model for initial EGD recommendation. We suggest that when considered in conjunction with the predictive clinical features of ALS diagnosis and dysphagia to both solids and liquids, the clinical frailty scale and American Society of Anesthesiologists physical status classification system scores may help clinicians anticipate gastrostomy when applied to patients with any neurologic disorder.},
}

@article {pmid40881516,
year = {2025},
author = {Swarnakar, R},
title = {Brain-Computer Interfaces in Rehabilitation: Implementation Models and Future Perspectives.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88873},
doi = {10.7759/cureus.88873},
pmid = {40881516},
issn = {2168-8184},
abstract = {Brain-computer interfaces (BCIs) represent an emerging advancement in rehabilitation, enabling direct communication between the brain and external devices to aid recovery in individuals with neurological impairments. BCIs can be classified into invasive, semi-invasive, non-invasive, or hybrid types. By interpreting neural signals and converting them into control commands, BCIs can bypass damaged pathways, offering therapeutic potential for conditions such as stroke, spinal cord injury, traumatic brain injury, and neurodegenerative diseases such as amyotrophic lateral sclerosis. BCIs' current applications, such as motor restoration via robotic exoskeletons and functional electrical stimulation, cognitive enhancement through neurofeedback and attention training, and communication tools for individuals with severe physical limitations, are largely being explored within research settings and are not yet part of routine clinical practice. Advances in EEG signal acquisition, machine learning, wearable and wireless systems, and integration with virtual reality are enhancing the clinical utility of BCIs by improving accuracy, adaptability, and usability. However, widespread clinical adoption faces challenges, including signal variability, training complexity, data privacy, and ethical and regulatory issues. Ethical challenges in BCI include issues related to the ownership and misuse of brain data, risks of neural interference, threats to autonomy and personal identity, as well as concerns around data privacy, user consent, emotional manipulation, and accountability in neural interventions. In this context, this editorial has also proposed one model (NEURO model checklist) for BCI implementation in rehabilitation. The future of BCIs in rehabilitation lies in developing personalized, closed-loop, and home-based systems, enabled by interdisciplinary collaboration among clinicians, engineers, neuroscientists, and policymakers. With continued research and ethical implementation, BCIs have the potential to transform neurorehabilitation and greatly enhance patient outcomes and quality of life.},
}

@article {pmid40879853,
year = {2025},
author = {Tu, JY},
title = {Letter to the Editor- The association between sarcopenic obesity and depression in middle-aged and elderly U.S. adults: insights from the NHANES study.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {260},
pmid = {40879853},
issn = {1720-8319},
mesh = {Humans ; *Sarcopenia/complications/psychology/epidemiology ; *Obesity/complications/epidemiology/psychology ; Aged ; *Depression/epidemiology/complications ; Middle Aged ; Nutrition Surveys ; United States/epidemiology ; Male ; Female ; },
abstract = {After reading "The association between sarcopenic obesity and depression in middle-aged and elderly U.S. adults: insights from the NHANES study", we sincerely appreciate Zhang et al.'s exploration of the relationship between sarcopenic obesity and depression in middle-aged and elderly populations, which provides new clinical perspectives for preventing sarcopenic obesity and depression. However, to more rigorously and clearly elucidate this relationship, several concerns must be addressed.},
}

Humans
*Sarcopenia/complications/psychology/epidemiology
*Obesity/complications/epidemiology/psychology
Aged
*Depression/epidemiology/complications
Middle Aged
Nutrition Surveys
United States/epidemiology
Male
Female

@article {pmid40879603,
year = {2025},
author = {Karimi, S and Ghaheri, A and Madani, H and Beheshti Maal, A and Sadri, B and Khodadoust, E and Sharafi, F and Vosough, M and Nabavi, SM},
title = {Intravenous vs intrathecal transplantation of allogeneic GMP/GCP compliant Wharton's jelly mesenchymal stromal cells in ALS patients: a phase I study.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/17582024.2025.2553499},
pmid = {40879603},
issn = {1758-2032},
abstract = {INTRODUCTION: There are a few therapeutic approaches for Amyotrophic Lateral Sclerosis (ALS) which can only slow down or stop the disease progression for a limited period of time. Since it has been proven that Mesenchymal Stromal Cells (MSCs) produce neurotrophic factors and have some neuroprotective effects, stem cell therapy has been proposed as an alternative or add-on treatment for ALS patients.

METHOD & MATERIAL: In this open-label clinical trial, two-repeated dose of 60 million GMP compliant Wharton's Jelly-derived Mesenchymal Stromal Cells (WJ-MSCs) were transplanted intrathecally (#6 patients) or intravenously (#6 patients) twice with a 3-month interval.

RESULTS: No adverse events related to the intervention or injected cells were reported. While no significant improvement in the total revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) score or overall clinical efficacy was achieved, patients reported improvements in specific sub-items such as salivation, swallowing, and their speech. Additionally, reductions in muscle tremors and fasciculations, as well as increased muscle strength were observed.

CONCLUSION: In conclusion, using WJ-MSCs is safe and feasible in ALS patients, but the efficacy of these cells should be assessed in future studies with more patients, different routes of cell administration, and maybe with higher doses of the injected cells.},
}

@article {pmid40879079,
year = {2025},
author = {Talbot, K and Thompson, AG},
title = {Unpacking the relationship between exercise and amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awaf310},
pmid = {40879079},
issn = {1460-2156},
}

@article {pmid40878928,
year = {2025},
author = {Chakraborty, A and Benassy, MN and Weil, D and Kundu, B},
title = {Optineurin Localization at the Centrosome, Spindle, and Midbody Implies Its Role in Cell Division.},
journal = {Cytoskeleton (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/cm.70015},
pmid = {40878928},
issn = {1949-3592},
abstract = {Optineurin (OPTN), a multifunctional cytosolic protein, is recognized as an autophagy adaptor. Its association with neurodegenerative diseases, like ALS, triggered extensive research. OPTN has been found in intracellular organelles, including the mitochondria, Golgi body, endosomes, microtubules, and the nucleus. The report of mitotic defects and delayed cell division in OPTN-depleted cells prompted us to explore OPTN's exact localization in the cell that could interfere with cell division assemblies. We used three distinct human cell lines, HeLa, HEK293, and SH-SY5Y, and probed them for OPTN localization using both centrosomal (Aurora A kinase, pericentrin, PCM1, Cep170, and γ-tubulin) and mitotic spindle markers (β-tubulin). Our immunofluorescence-based detection using wide-field fluorescence, confocal, and structured illumination microscopy (SIM) placed OPTN at the centrosome, which remained associated with the centriole after duplication and their migration during mitosis. OPTN was also observed at the junction of daughter cells during cytokinesis. Our finding reveals unmapped localizations of OPTN with key cytosolic assemblies that are directly involved in cell division.},
}

@article {pmid40878817,
year = {2025},
author = {Lester, DG and Talbot, K and Turner, MR and Thompson, AG and , },
title = {A Validated Model to Predict Severe Weight Loss in Amyotrophic Lateral Sclerosis.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70129},
pmid = {40878817},
issn = {2328-9503},
support = {Lester/2450/795/MNDA_/Motor Neurone Disease Association/United Kingdom ; Thompson/Jan20/952-795/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/T006927/1/MRC_/Medical Research Council/United Kingdom ; MR/Y001095/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {Severe weight loss in amyotrophic lateral sclerosis (ALS) is common, multifactorial, and associated with shortened survival. Using longitudinal weight data from over 6000 patients with ALS across three cohorts, we built an accelerated failure time model to predict the risk of future severe (≥ 10%) weight loss using five single-timepoint clinical predictors: symptom duration, revised ALS Functional Rating Scale, site of onset, forced vital capacity, and age. Model performance and generalisability were evaluated using internal-external cross-validation and random-effects meta-analysis. The overall concordance statistic was 0.71 (95% CI 0.63-0.79), and the calibration slope and intercept were 0.91 (0.69-1.13) and 0.05 (-0.11-0.21). This study highlights clinical factors most associated with severe weight loss in ALS and provides the basis for a stratification tool.},
}

@article {pmid40878665,
year = {2025},
author = {Abrahao, A and Da Silva, P and Ciepielewska, M and Zinman, L},
title = {Real-world safety and tolerability of intravenous edaravone in patients with amyotrophic lateral sclerosis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/17582024.2025.2552610},
pmid = {40878665},
issn = {1758-2032},
abstract = {AIMS: This retrospective cohort study describes real-world safety and tolerability outcomes in United States-based edaravone-treated patients with ALS.

PATIENTS & METHODS: Amerita Specialty Infusion Services provided IV edaravone to patients with ALS treated with their first dose between 25 September 2017-30 September 2022. Mean ALS Functional Rating Scale-Revised (ALSFRS-R) scores and forced vital capacity (FVC) %-predicted measures were recorded within ± 100 days from care initiation to approximate baseline values.

RESULTS: Included patients (n = 243) received/were still receiving IV edaravone/edaravone oral suspension as of 30 September 2022. At initiation, 66.7% were male, mean age ± SD was 61.2 ± 11.2 years, and 61.3% were covered by government insurance. In patients with provider-recorded ALSFRS-R (n = 115) and FVC (n = 84) %-predicted measures within ± 100 days from care initiation, mean ± SD values were 35.1 ± 8.9 and 72.3% ± 21.7%, respectively. Mean ± SD therapy duration was 13.5 ± 11.4 months. Discontinuation reasons included death/hospice (n = 82), patient's choice (n = 38), doctor's choice (n = 31), insurance (n = 18), and other (n = 12). Reasons for IV edaravone discontinuation and IV edaravone administration access device were not associated.

CONCLUSIONS: Treatment discontinuation was primarily related to ALS disease progression/death, rather than safety or tolerability. This study representative of real-world patients with ALS suggests that edaravone showed consistent safety and tolerability profiles with previous studies.},
}

@article {pmid40878249,
year = {2025},
author = {Silva, MM and Cunha, EM and Briois, V and Rochet, A},
title = {Unraveling hydride dynamics on cubic palladium nanoparticles.},
journal = {Physical chemistry chemical physics : PCCP},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5cp02672e},
pmid = {40878249},
issn = {1463-9084},
abstract = {Palladium-based materials exhibit a high affinity for hydrogen molecules, enabling the effortless formation of a hydride phase. This property is widely exploited in several catalytic reactions and hydrogen storage materials. However, the effects of morphological parameters, support interactions, and formation kinetics remain incompletely understood. In this work, we applied in situ time-resolved X-ray absorption spectroscopy (XAS) to investigate the impact of nanoparticle sizes and support materials on the dynamic formation of palladium hydrides during thermal treatment under H2. A detailed analysis using multivariate curve resolution with alternating least squares (MCR-ALS) enabled the extraction of concentration profiles and the identification of pure species involved in the process, thereby revealing distinct kinetic behaviours across the samples. This study provides valuable insights into how particle size and support influence the kinetics of hydrogen absorption in palladium systems, which can significantly impact catalytic performance.},
}

@article {pmid40877115,
year = {2025},
author = {Hu, N and Ding, J and Tian, H and Shen, D and Yang, X and Niu, J and Liu, M and Cui, L},
title = {Impacts of oral supplementation of vitamin B12 and plasma levels of homocysteine on progression and survival in a Chinese ALS cohort.},
journal = {Neurological research},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/01616412.2025.2553147},
pmid = {40877115},
issn = {1743-1328},
abstract = {OBJECTIVE: We investigate the impact of plasma levels of folate, vitamin B12 (VB12), homocysteine (HCY) and oral supplementation of folate and VB12 on amyotrophic lateral sclerosis (ALS) progression and survival.

METHODS: Patients with sporadic ALS were consecutively enrolled and regularly followed up. Oral supplementation of folate and VB12 was recommended to all involved patients. Tests of plasma levels of folate, VB12 and HCY were conducted before or after medication.

RESULTS: A total of 120 sporadic ALS patients with results of plasma folate, VB12 or HCY were finally included. Oral supplementation of VB12 significantly increased the plasma levels of folate (p < 0.01) and VB12 (p < 0.01), and lower HCY (p < 0.001). The progression rate of ALS patients in the first 3-6 months was negatively related to the plasma level of VB12 (p = 0.008). After taking VB supplements, the progression rate in the first 3-6 months was comparable to previous progression rate (p = 0.102) and significantly lower than that in the 9-12 month follow-up (p < 0.01). There was no significant difference in survival time between the two groups that took VB12 and those who did not take it neither between patients with high and low serum levels of folate, VB12 or HCY.

CONCLUSION: Oral intake of VB12 supplements may significantly increase plasma levels of folate and VB12 and decrease plasma levels of HCY in ALS patients. Oral supplementation of folate and VB12, and subsequent high levels of VB12 in serum, may lower the ALS progression at the early stages but show no significant impact on ALS survival time.},
}

@article {pmid40876628,
year = {2025},
author = {Pytel, D and Longo, JF},
title = {The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2025.07.011},
pmid = {40876628},
issn = {1525-2191},
abstract = {Proteinopathies are neurodegenerative disorders that are characterized by accumulation of misfolded toxic protein aggregates that lead to synaptic and neuronal dysfunction. Though genetically, clinically and pathologically distinct, a common feature of these diseases is disruption of protein homeostasis (proteostasis), which causes accumulation of misfolded proteins. The machinery mediating proteostasis exquisitely balances and interlaces protein synthesis, protein folding and trafficking, and protein degradation processes within the proteostasis network to maintain homeostasis. The proteostasis network governs a functional and dynamic proteome by modulating the timing, location, and stoichiometry of protein expression, surveillance and maintenance of protein folding and removal of misfolded or excess proteins. Although a functional proteome is essential for the health of all cell types, this is especially true for neurons which are prone to enhanced cellular stress. Aging is the most important risk factor for proteostasis decline and the development of proteinopathies. However, germline and somatic mutations can also functionally impair components of the proteostasis network. Post-mitotic cells, particularly neurons, are rendered further susceptible to proteostasis dysfunction due to their extended lifespan. This review discusses the interconnections between the functional components mediating proteostasis in neuronal cells and how aberrations in proteostasis contribute to neuronal dysfunction and disease.},
}

@article {pmid40876427,
year = {2025},
author = {Ibrahim, SI and Zaher, DM and Hersi, FA and Hamouda, AO and Al Hindawi, MA and Omar, HA},
title = {Repurposing edaravone in oncology: Bridging antioxidant defense and immune modulation.},
journal = {International immunopharmacology},
volume = {164},
number = {},
pages = {115413},
doi = {10.1016/j.intimp.2025.115413},
pmid = {40876427},
issn = {1878-1705},
abstract = {Edaravone, a synthetic free radical scavenger originally approved for neurological disorders such as stroke and amyotrophic lateral sclerosis (ALS), is gaining attention for its emerging potential role in cancer. Beyond its well-established antioxidant properties, edaravone demonstrates significant anti-inflammatory and immunomodulatory activities, including the inhibition of key pathways such as NF-κB, JAK2/STAT3, and TLR4/IL-6, suggesting potential to modulate immune responses within the tumor microenvironment. This review discusses how edaravone disrupts oncogenic signaling, induces cell cycle arrest, and enhances apoptosis, particularly in cancer stem cells and therapy-resistant models. It also examines edaravone's dual role in combination therapies, where it may improve the cytotoxicity of chemotherapeutic and radiotherapeutic agents while simultaneously protecting normal tissues from treatment-induced toxicities. By linking mechanistic insights with therapeutic outcomes, this review highlights the rationale for repurposing edaravone as a potential adjuvant in cancer therapy. Although clinical data are currently limited, preliminary findings are encouraging and warrant further investigation into edaravone's potential use in cancer treatment regimens.},
}

@article {pmid40875997,
year = {2025},
author = {Kaufman Goldberg, T and Hadlock, TA},
title = {Invited Commentary on: Frants et al.'s "Dual Innervation of the Depressor Labii Inferioris and Implications for Deep Plane Facelift and Structural Neck Contouring": Converging Evidence for Cervical Branch Innervation of the Depressor Labii Inferioris.},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {27},
number = {5},
pages = {406-407},
doi = {10.1177/26893614251370279},
pmid = {40875997},
issn = {2689-3622},
}

@article {pmid40875690,
year = {2025},
author = {Abdallah, W and Picard-Turcot, MA and Lafontaine-Trudel, I and Codsi, E and Wavrant, S and Carmant, L and Raboisson, MJ and Khalil, A and Audibert, F},
title = {Prediction of dual twin survival after laser for twin-to-twin transfusion syndrome.},
journal = {Fetal diagnosis and therapy},
volume = {},
number = {},
pages = {1-14},
doi = {10.1159/000547995},
pmid = {40875690},
issn = {1421-9964},
abstract = {OBJECTIVES: To evaluate the predictive value of sonographic parameters at diagnosis of Twin-to-Twin Transfusion Syndrome (TTTS) treated with fetoscopic laser photocoagulation for post-natal dual twin survival, and to validate Krispin et al's calculator.

METHODS: This is a retrospective cohort study of cases of TTTS treated by FLPC. The primary outcome was dual survival 30 days after delivery. The calculator used preoperative variables: donor's estimated fetal weight (EFW)<10th centile, intertwin growth discordance >25%, anterior placenta, pulsatility index (PI) in the umbilical artery (UA), ductus venosus (DV) and middle cerebral artery (MCA), with scores ranging 0-300.

RESULTS: Among 157 patients, 84 (53.5%) had dual twin survival (A), compared to 73 (46.5%) with one or no survivors (B). No significant differences were seen in donor's EFW <10th centile (57.1%(A) vs. 57.5%(B), p=0.96), intertwin growth discordance (26.2%(A) vs. 38.4%(B) p=0.95), rates of PI>95th centile in the donor's UA and DV, and PI<5th centile in the MCA (p>0.05). However, a significant difference was found for anterior placenta (38.1% (A) vs. 58.9% (B), p=0.009). The observed dual survival was higher than predicted for scores ≥100.

CONCLUSIONS: We did not externally validate the calculator of dual survival after laser for TTTS, especially for elevated scores.},
}

@article {pmid40875372,
year = {2025},
author = {Ghaffari, LT and Welebob, EA and Newton, SEB and Boehringer, AV and Cyliax, KL and Pasinelli, P and Trotti, D and Haeusler, AR},
title = {Neuronal Activity-Dependent Gene Dysregulation in C9orf72 i[3]Neuronal Models of ALS/FTD Pathogenesis.},
journal = {American journal of physiology. Cell physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpcell.00238.2025},
pmid = {40875372},
issn = {1522-1563},
support = {RF1NS114128//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS114128//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS109150//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; NA//Farber Family Foundation/ ; NA//Aldrich Foundation/ ; },
abstract = {The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9orf72 (C9) gene is the most common cause of ALS and FTD. Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE iPSC-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization, or a blockade of K[+] channels, followed by RNA sequencing, induces a temporally divergent activity-dependent transcriptome of C9-NRE cortical neurons compared to healthy controls. This study provides new insights into how neuronal activity influences the ALS/FTD-associated transcriptome, offering a dataset that enables further exploration of pathways necessary for conferring neuronal resilience or degeneration.},
}

@article {pmid40875341,
year = {2025},
author = {Dang, J and Xiao, S},
title = {A meta-analytic reassessment of the vicious cycle of psychopathology and stressful life events: Commentary on Rnic et al. (2023).},
journal = {Psychological bulletin},
volume = {151},
number = {7},
pages = {930-939},
doi = {10.1037/bul0000475},
pmid = {40875341},
issn = {1939-1455},
mesh = {Humans ; *Stress, Psychological/psychology ; *Life Change Events ; *Mental Disorders/psychology/epidemiology ; Psychopathology ; },
abstract = {Rnic et al. (2023) conducted a comprehensive multilevel meta-analysis examining the stress generation hypothesis across various forms of psychopathology. They utilized the bivariate correlation between psychopathology at Time 1 and stress at Time 2 to estimate effect sizes. To address potential confounding from baseline stress assessments, we reanalyzed the data by (a) using the cross-lagged association in a multilevel meta-analysis to examine longitudinal links between Time 1 psychopathology and Time 2 stress and (b) incorporating Time 1 stress as a control variable in a meta-analytic structural equation model. Based on a subset of Rnic et al.'s original data set (33 studies with 18,684 participants and 126 effect sizes), our findings revealed cross-lagged associations of rC.L = .12 for the predictive effect of baseline psychopathology, especially internalizing psychopathology, on subsequent dependent stress and rC.L = .06 for independent stress. These effects were homogeneous across diverse samples, measures, and contexts. Moreover, even after controlling for Time 1 stress, dependent stress continued to mediate the relationship between baseline psychopathology and subsequent symptoms, whereas independent stress did not mediate, underscoring the role of dependent stress in perpetuating the cycle of stress and psychopathology. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

Humans
*Stress, Psychological/psychology
*Life Change Events
*Mental Disorders/psychology/epidemiology
Psychopathology

@article {pmid40875336,
year = {2025},
author = {Yuan, Z and Yin, J and Sun, J},
title = {The paradox of team conflict revisited: An updated meta-analysis of the team conflict-team performance relationships.},
journal = {The Journal of applied psychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/apl0001315},
pmid = {40875336},
issn = {1939-1854},
abstract = {The possibility that team conflict, especially task conflict, might improve team performance has stimulated a large body of empirical research that continues to grow to this day. Nevertheless, 12 years has passed since de Wit et al.'s (2012) comprehensive meta-analysis. To synthesize the even larger body of empirical evidence now available, we provide an updated meta-analysis of the team conflict-team performance relationships by revisiting the population average estimates and their effect size heterogeneity. Given the recent developments in the team conflict literature, we also incorporate status conflict into our synthesis. Moreover, to shed light on the contextual factors that may help explain the heterogeneous team conflict-team performance relationships, we examine a host of moderators pertaining to national culture, team features, and research methods. Our results based on psychometric meta-analysis indicate that all four team conflict dimensions (i.e., task conflict, relationship conflict, process conflict, and status conflict) are negatively related to team performance. Moreover, the relationships of task conflict and relationship conflict with team performance have substantial cross-situation heterogeneity. Examining the contingencies of these heterogeneous relationships, our metaregression analyses reveal that national culture (e.g., individualism), team features (e.g., team performance facet), and methodological factors (e.g., team conflict scale) all play important roles in helping to explain the mixed effects of team conflict on team performance. Based on our quantitative synthesis, we discuss the implications for the next waves of team conflict research. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

@article {pmid40874900,
year = {2025},
author = {Shive, M and Hawryluk, E and Drucker, AM and Frazer-Green, L},
title = {Response to Chu et al's "Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.07.061},
pmid = {40874900},
issn = {1097-6787},
}

@article {pmid40873038,
year = {2025},
author = {Dulski, J and Boddapati, AK and Risi, B and Iruzubieta, P and Orlacchio, A and Fernández-Torrón, R and Castillo-Triviño, T and López de Munain, A and Vucic, S and Padovani, A and Kaat, LD and Barakat, TS and Petrucelli, L and Prudencio, M and Landers, JE and Weishaupt, JH and Prokop, A and Filosto, M and Wszolek, ZK and Pant, DC},
title = {Targeted plasma proteomics uncover proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100498},
doi = {10.1016/j.xhgg.2025.100498},
pmid = {40873038},
issn = {2666-2477},
abstract = {KIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a multiplex NULISA targeted platform to analyze plasma proteome from KIF5A-linked SPG10, ALS individuals and compared to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function, and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG10 individuals. Moreover, these findings can now be taken forward to gain mechanistic understanding of axonopathies linking to N- versus C-terminal KIF5A variants affecting both central and peripheral nervous systems.},
}

@article {pmid40872233,
year = {2025},
author = {Garcia-Sherman, MC and Hamid, SA and Jackson, DN and Thomas, J and Lipke, PN},
title = {Functional Amyloids in Adhesion of Non-albicans Candida Species.},
journal = {Pathogens (Basel, Switzerland)},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/pathogens14080723},
pmid = {40872233},
issn = {2076-0817},
support = {1R01GM098616-01/NH/NIH HHS/United States ; },
mesh = {Humans ; *Cell Adhesion ; *Candida/physiology/metabolism ; *Amyloid/metabolism ; Biofilms/growth & development ; Fungal Proteins/metabolism ; Candida albicans ; Candidiasis/microbiology ; Epithelial Cells/microbiology ; },
abstract = {Candida fungal species are the most common fungal opportunistic pathogens. Their ability to form antifungal resistant biofilms contributes to their increasing clinical frequency. These fungi express surface-anchored adhesins including members of the Als family. These adhesins mediate epithelial adhesion, aggregation, and biofilm formation. Many of the adhesins contain cross-β core sequences that form amyloid-like protein aggregates on the fungal surface. The aggregates mediate high-avidity bonding that contributes to biofilm establishment and persistence. Accordingly, autopsy sections from individuals with candidiasis and other mycoses have amyloids within abscesses. An amyloid-forming peptide containing a sequence from Candida albicans Als5 bound to C. albicans, C. tropicalis, and C. parapsilosis. C. albicans and C. tropicalis aggregated with beads coated with serum albumin, and the aggregates stained with the amyloid-binding dye thioflavin T. Additionally, an Als5-derived amyloid-inhibiting peptide blocked cell aggregation. The amyloid-inhibiting peptide also blocked C. albicans, C. tropicalis, and C. parapsilosis adhesion to monolayers of FaDu epithelial cells. These results show the involvement of amyloid-like interactions in pathogenesis in several Candida species.},
}

Humans
*Cell Adhesion
*Candida/physiology/metabolism
*Amyloid/metabolism
Biofilms/growth & development
Fungal Proteins/metabolism
Candida albicans
Candidiasis/microbiology
Epithelial Cells/microbiology

@article {pmid40871062,
year = {2025},
author = {Yang, HM},
title = {Overcoming the Blood-Brain Barrier: Advanced Strategies in Targeted Drug Delivery for Neurodegenerative Diseases.},
journal = {Pharmaceutics},
volume = {17},
number = {8},
pages = {},
doi = {10.3390/pharmaceutics17081041},
pmid = {40871062},
issn = {1999-4923},
support = {03-2025-0200//Seoul National University Hospital/ ; },
abstract = {The increasing global health crisis of neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease is worsening because of a rapidly increasing aging population. Disease-modifying therapies continue to face development challenges due to the blood-brain barrier (BBB), which prevents more than 98% of small molecules and all biologics from entering the central nervous system. The therapeutic landscape for neurodegenerative diseases has recently undergone transformation through advances in targeted drug delivery that include ligand-decorated nanoparticles, bispecific antibody shuttles, focused ultrasound-mediated BBB modulation, intranasal exosomes, and mRNA lipid nanoparticles. This review provides an analysis of the molecular pathways that cause major neurodegenerative diseases, discusses the physiological and physicochemical barriers to drug delivery to the brain, and reviews the most recent drug targeting strategies including receptor-mediated transcytosis, cell-based "Trojan horse" approaches, gene-editing vectors, and spatiotemporally controlled physical methods. The review also critically evaluates the limitations such as immunogenicity, scalability, and clinical translation challenges, proposing potential solutions to enhance therapeutic efficacy. The recent clinical trials are assessed in detail, and current and future trends are discussed, including artificial intelligence (AI)-based carrier engineering, combination therapy, and precision neuro-nanomedicine. The successful translation of these innovations into effective treatments for patients with neurodegenerative diseases will require essential interdisciplinary collaboration between neuroscientists, pharmaceutics experts, clinicians, and regulators.},
}

@article {pmid40870776,
year = {2025},
author = {Semyalo, D and Joshi, R and Kim, Y and Omia, E and Alal, LB and Kim, MS and Baek, I and Cho, BK},
title = {Short-Wavelength Infrared Hyperspectral Imaging and Spectral Unmixing Techniques for Detection and Distribution of Pesticide Residues on Edible Perilla Leaves.},
journal = {Foods (Basel, Switzerland)},
volume = {14},
number = {16},
pages = {},
doi = {10.3390/foods14162864},
pmid = {40870776},
issn = {2304-8158},
support = {N/A//Chungnam National University/ ; },
abstract = {Pesticide residue analysis of agricultural produce is vital because of associated health concerns, highlighting the need for effective non-destructive techniques. This study introduces a method that combines short-wavelength infrared hyperspectral imaging with spectral unmixing to detect chlorfenapyr and azoxystrobin residues on perilla leaves. Sixty-six leaves were treated with pesticides at concentrations between 0 and 0.06%. The study utilized multicurve resolution-alternating least squares (MCR-ALS), a spectral unmixing method, to identify and visualize the distribution of pesticide residues. This technique achieved lack-of-fit values of 1.03% and 1.78%, with an explained variance of 99% for both pesticides. Furthermore, a quantitative model was developed that integrates insights from MCR-ALS with Gaussian process regression to estimate chlorfenapyr residue concentrations, resulting in a root mean square error of double cross-validation (RMSEV) of 0.0012% and a double cross-validation coefficient of determination (R[2]v) of 0.99. Compared to other chemometric approaches, such as partial least squares regression and support vector regression, the proposed integrated method decreased RMSEV by 67.57% and improved R[2]v by 2.06%. The combination of hyperspectral imaging with spectral unmixing offers advancements in the real-time monitoring of agricultural product safety, supporting the delivery of high-quality fresh vegetables to consumers.},
}

@article {pmid40870005,
year = {2025},
author = {Jeong, J and Kim, J and Kim, MS},
title = {Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.},
journal = {Genes},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/genes16080957},
pmid = {40870005},
issn = {2073-4425},
mesh = {Humans ; *Mitochondria/metabolism/pathology/genetics ; *Stress, Physiological ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics ; },
abstract = {BACKGROUND: The mitochondrial integrated stress response (ISR) represents a fundamental cellular adaptation mechanism with dual protective and pathological roles. We critically analyzed current literature on ISR mechanisms, focusing on recent paradigm shifts including the 2020 discovery of the OMA1-DELE1-HRI axis, emerging controversies over context-dependent activation patterns, and the January 2025 clinical trial failures that have reshaped the therapeutic landscape.

METHODS: We reviewed recent literature (2020-2025) examining ISR mechanisms, clinical trials, and therapeutic developments through comprehensive database searches.

RESULTS: The field has evolved from simple linear pathway models to recognition of complex, context-dependent networks. Recent findings reveal that ISR activation mechanisms vary dramatically based on cellular metabolic state, with distinct pathways operating in proliferating versus differentiated cells. The "dark microglia" phenotype in neurodegeneration and DR5-mediated apoptotic switches exemplify pathological ISR manifestations, while adaptive responses include metabolic reprogramming and quality control enhancement.

CONCLUSIONS: The 2025 failures of DNL343 and ABBV-CLS-7262 in ALS trials underscore the need for precision medicine approaches that account for context-dependent ISR functions, temporal dynamics, and disease-specific mechanisms.},
}

Humans
*Mitochondria/metabolism/pathology/genetics
*Stress, Physiological
Animals
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics

@article {pmid40869392,
year = {2025},
author = {Șerban, M and Toader, C and Covache-Busuioc, RA},
title = {Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26168072},
pmid = {40869392},
issn = {1422-0067},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology/diagnosis ; Humans ; *Biomarkers/metabolism ; Disease Progression ; Animals ; Mitochondria/metabolism ; Precision Medicine ; Neurofilament Proteins/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is still a heterogeneous neurodegenerative disorder that can be identified clinically and biologically, without a strong set of biomarkers that can adequately measure its fast rate of progression and molecular heterogeneity. In this review, we intend to consolidate the most relevant and timely advances in ALS biomarker discovery, in order to begin to bring molecular, imaging, genetic, and digital areas together for potential integration into a precision medicine approach to ALS. Our goal is to begin to display how several biomarkers in development (e.g., neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), TDP-43 aggregates, mitochondrial stress markers, inflammatory markers, etc.) are changing our understanding of ALS and ALS dynamics. We will attempt to provide a framework for thinking about biomarkers in a systematic way where our candidates are not signals alone but part of a tethered pathophysiological cascade. We are particularly interested in the fast progressor phenotype, a devastating and under-characterized subset of ALS due to a rapid axonal degeneration, early respiratory failure, and very short life span. We will try to highlight the salient molecular features of this ALS subtype, including SOD1 A5V toxicity, C9orf72 repeats, FUS variants, mitochondrial collapse, and impaired autophagy mechanisms, and relate these features to measurable blood and CSF (biomarkers) and imaging platforms. We will elaborate on several interesting tools, for example, single-cell transcriptomics, CSF exosomal cargo analysis, MRI techniques, and wearable sensor outputs that are developing into high-resolution windows of disease progression and onset. Instead of providing a static catalog, we plan on providing a conceptual roadmap to integrate biomarker panels that will allow for earlier diagnosis, real-time disease monitoring, and adaptive therapeutic trial design. We hope this synthesis will make a meaningful contribution to the shift from observational neurology to proactive biologically informed clinical care in ALS. Although there are still considerable obstacles to overcome, the intersection of a precise molecular or genetic association approach, digital phenotyping, and systems-level understandings may ultimately redefine how we monitor, care for, and treat this challenging neurodegenerative disease.},
}

*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology/diagnosis
Humans
*Biomarkers/metabolism
Disease Progression
Animals
Mitochondria/metabolism
Precision Medicine
Neurofilament Proteins/metabolism

@article {pmid40869205,
year = {2025},
author = {Lewandowski, D and Konieczny, M and Różycka, A and Chrzanowski, K and Owecki, W and Kalinowski, J and Stepura, M and Jagodziński, P and Dorszewska, J},
title = {Cathepsins in Neurological Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26167886},
pmid = {40869205},
issn = {1422-0067},
mesh = {Humans ; *Cathepsins/metabolism ; Animals ; *Nervous System Diseases/metabolism/pathology ; Lysosomes/metabolism ; Biomarkers/metabolism ; },
abstract = {Cathepsins, a family of lysosomal proteases, play critical roles in maintaining cellular homeostasis through protein degradation and modulation of immune responses. In the central nervous system (CNS), their functions extend beyond classical proteolysis, influencing neuroinflammation, synaptic remodeling, and neurodegeneration. Emerging evidence underscores the crucial role of microglial cathepsins in the pathophysiology of several neurological disorders. This review synthesizes current knowledge on the involvement of cathepsins in a spectrum of CNS diseases, including Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, Huntington's disease, and ischemic stroke. We highlight how specific cathepsins contribute to disease progression by modulating key pathological processes such as α-synuclein and amyloid-β clearance, tau degradation, lysosomal dysfunction, neuroinflammation, and demyelination. Notably, several cathepsins demonstrate both neuroprotective and pathogenic roles depending on disease context and expression levels. Additionally, the balance between cathepsins and their endogenous inhibitors, such as cystatins, emerges as a critical factor in CNS pathology. While cathepsins represent promising biomarkers and therapeutic targets, significant gaps remain in our understanding of their mechanistic roles across diseases. Future studies focusing on their regulation, substrate specificity, and interplay with genetic and epigenetic factors may yield novel strategies for early diagnosis and disease-modifying treatments in neurology.},
}

Humans
*Cathepsins/metabolism
Animals
*Nervous System Diseases/metabolism/pathology
Lysosomes/metabolism
Biomarkers/metabolism

@article {pmid40868609,
year = {2025},
author = {Lisiecka, D and Dyson, N and Malpress, K and Smith, A and McNeice, E and Shack, P and Hutchinson, K},
title = {'Finally, in Hands I Can Trust': Perspectives on Trust in Motor Neurone Disease Care.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {16},
pages = {},
doi = {10.3390/healthcare13161994},
pmid = {40868609},
issn = {2227-9032},
abstract = {Integrated multidisciplinary care is recognised as essential for people living with motor neurone disease (PlwMND) and their families. The values underpinning integrated care, such as person-centredness, respect, empowerment, and co-production, are central to delivering meaningful and comprehensive support. Trust is an essential yet often overlooked element of effective person- and family-centred integrated care, particularly for PlwMND. While specialist multidisciplinary MND clinics represent the benchmark for evidence-based care, many PlwMND and their families depend significantly on local and community-based support services to maintain quality of life. Trust directly influences their engagement with these services and the continuity of care provided. Trust enables understanding of personal priorities and how they change as the disease progresses, ultimately allowing for person-centred care to happen. Trust is necessary to enable service co-production, which is a strong value of integrated care. Research highlights seven key domains of support essential to PlwMND and their carers: practical, social, informational, psychological, physical, emotional, and spiritual. Effective integrated care requires strong relationships built upon trust, shared decision-making, respect for individuality, and clear communication. Furthermore, due to the rapidly progressive nature of MND, care priorities and perceived symptom burdens may shift significantly over short periods, making flexible, temporally sensitive approaches critical. A dynamic, inclusive model of decision-making that fosters autonomy within and regular co-review of needs is recommended. This perspective paper examines how person- and family-centred integrated care is currently being delivered, what is working well, and how these practices can be further strengthened to enhance the care experiences of PlwMND, their families, and the health and social care providers involved. This paper builds on both theoretical knowledge and clinical experience to offer our perspective on the critical role of trust in co-producing integrated care for PlwMND. It brings together the voices of clinicians and researchers, alongside those with lived experience of MND. We propose a diagram of care that embeds the core values of integrated, person-centred care within the specific context of MND. Our aim is to enhance collaborative practices, strengthen cross-sector partnerships, and ultimately improve the care experiences for professionals, PlwMND, and their families.},
}

@article {pmid40868276,
year = {2025},
author = {Voicu, V and Toader, C and Șerban, M and Covache-Busuioc, RA and Ciurea, AV},
title = {Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteostatic Collapse, and Network Failure Across the CNS.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/biomedicines13082025},
pmid = {40868276},
issn = {2227-9059},
abstract = {Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization-spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways-including PI3K-AKT-mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades-undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome-lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3-CR3 axis), and excitatory-inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network "meaning-making"-a collapse of coordinated signal interpretation, triage prioritization, and adaptive response-the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning-a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration.},
}

@article {pmid40868211,
year = {2025},
author = {Flor, J and Silveira, AT and Martins, IA and Otero, LB and Silva, FM and Vizuete, AFK and Wink, MR and Rigatto, K},
title = {Biological Actions of Alamandine: A Scoping Review.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/biomedicines13081957},
pmid = {40868211},
issn = {2227-9059},
abstract = {Objective: This scoping review aims to comprehensively map the existing literature on the mechanisms of action of Alamandine (ALA), a peptide within the renin-angiotensin system, and its effects across various physiological systems. Materials and Methods: Utilizing the Joanna Briggs Institute methodology, a thorough search of databases including PubMed, Embase, Scopus, and Web of Science was conducted up to 30 January 2025. The review focused on identifying studies that explore the biological and therapeutic roles of ALA in different contexts, incorporating in vivo, in vitro, and in silico research. Results: A total of 590 records were initially identified, with 25 meeting the eligibility criteria for inclusion in this review. China emerged as the leading contributor to the research in this area, with a significant focus on the cardiovascular system. The studies revealed that ALA exhibits a range of beneficial effects, including anti-inflammatory, vasodilatory, antifibrotic, and antiapoptotic actions. These effects are primarily mediated through the inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway and modulation of the nitric oxide pathway. The review also highlighted AL's potential in mitigating oxidative stress and its implications in treating cardiovascular diseases, fibrosis, and cancer. Conclusions: The findings suggest that ALA holds significant therapeutic potential, offering antihypertensive, anti-inflammatory, antifibrotic, and anticancer benefits without notable adverse effects, warranting further research to explore its full potential and mechanism of action.},
}

@article {pmid40866928,
year = {2025},
author = {Tsang, VSK and Malaspina, A and Henson, SM},
title = {The metabolic intersection between immunosenescence and neuroinflammation in amyotrophic lateral sclerosis.},
journal = {Journal of inflammation (London, England)},
volume = {22},
number = {1},
pages = {36},
pmid = {40866928},
issn = {1476-9255},
support = {BBX009610/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons. Although it is traditionally viewed as a neuron-centric disease, neurodegeneration is increasingly linked to immunosenescence and age-related immune dysfunction, but the mechanisms connecting immune ageing to neurodegeneration remain poorly understood. In this review, we explore how metabolic reprogramming, especially the loss of metabolic plasticity in senescent immune cells, drives neuroinflammation in ALS. Senescent immune cells, including microglia and T cells, exhibit mitochondrial dysfunction, redox imbalance, impaired autophagy, and altered nutrient-sensing pathways that impair their homeostatic and reparative capacities. These cells adopt a metabolically demanding pro-inflammatory phenotype, sustaining an inflammatory secretome while promoting glial activation and neuronal damage. Finally, we discuss how targeting immunometabolic pathways may offer new therapeutic opportunities to restore immune balance, mitigate neuroinflammation, and potentially slow ALS progression. Understanding the metabolic basis of immune ageing is essential for developing effective, age-tailored interventions for ALS.},
}

@article {pmid40866479,
year = {2025},
author = {Waheed, ZA and Colagar, AH and Seyedalipour, B and Baziyar, P},
title = {Uncovering the protein aggregation process through effect of G41D mutant SOD1 charge variation in ALS disease.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {31661},
pmid = {40866479},
issn = {2045-2322},
abstract = {Neurodegenerative disorders are a group of hereditary and sporadic conditions that are characterized by progressive nervous system dysfunctions. Mutations in the gene encoding human superoxide dismutase 1 (hSOD1) were among the first to be proposed in line with the protein aggregation theory for ALS disease. This study aimed to characterize the (G41D) mutation/charge effects on the biochemical and biophysical properties of the SOD1 structure through computational and experimental methods. The computed average values of RMSD, RMSF, and Rg demonstrate that mutation results in a loss of conformational stability, increased flexibility, and greater compactness, all supporting the observed aggregation. The G41D mutant revealed distinct changes in β-sheet content compared to WT-SOD1 under amyloidogenic conditions, as confirmed by FTIR spectroscopy. Furthermore, the formation of amyloid/amorphous species was identified using ThT/ANS fluorescence and confirmed by TEM analysis. Mutations that alter the net negative charge of the SOD1 protein are crucial in misfolding and shortening the lag phase in SOD1 aggregation. Our results provide supporting evidence that these charge alterations, alongside amyloid-inducing agents at near-physiological pH, significantly contribute to the formation of amyloid-like species. Therefore, studying the G41D mutation may provide valuable insights into the mechanisms of fALS-associated aggregate formation, which holds promise for the development of highly effective inhibitors in reducing aggregates and therapeutic potential.},
}

@article {pmid40865732,
year = {2025},
author = {Deighen, MR and Fakult, NJ and Mani, KA and Cullison, CR and Wang, M and Bordeaux, JS and Carroll, BT and Rothermel, LD and Zaorsky, NG},
title = {Response to Sheu et al., "Comments on Fakult et al.'s 'Epidemiology of Merkel Cell Carcinoma in the United States'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.08.055},
pmid = {40865732},
issn = {1097-6787},
}

@article {pmid40865726,
year = {2025},
author = {Li, Y and Wang, Y and Li, Y and Jia, X and Du, X},
title = {[Response][to][Pavlović] '[s] "[Response][to][Li][et][al.'s] '[Therapeutic efficacy of platelet-rich plasma combining with microneedling and topical minoxidil in refractory severe androgenic alopecia]'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.08.056},
pmid = {40865726},
issn = {1097-6787},
}

@article {pmid40865585,
year = {2025},
author = {Xu, C and Naudet, F and Kim, TT and Hengartner, MP and Horowitz, MA and Kirsch, I and Moncrieff, J and Pigott, E and Plöderl, M},
title = {Large responses to antidepressants or methodological artifacts? A secondary analysis of STAR*D, a single-arm, open-label, non-industry antidepressant trial.},
journal = {Journal of clinical epidemiology},
volume = {},
number = {},
pages = {111943},
doi = {10.1016/j.jclinepi.2025.111943},
pmid = {40865585},
issn = {1878-5921},
abstract = {OBJECTIVES: To replicate Stone et al.'s (2022) [1] finding that the distribution of response in clinical antidepressant trials is trimodal with large, medium-effect, and small subgroups.

METHODS: To apply finite mixture modeling to pre-post Hamilton Depression Rating Scale (HDRS) differences (n = 2184) of STAR*D study's level 1, a single-arm, open-label study. For a successful replication, the best fitting model had to be trimodal, with comparable components as in Stone et al. Secondary/sensitivity analyses repeated the analysis for different baseline levels of depression severity, imputed values, and patient-reported depression symptoms.

RESULTS: The best fitting models were either bimodal or trimodal but the trimodal solution did not meet criteria for replication. The bimodal model had one component with HDRS mean change of M = -13.0, SD = 6.7 and included 65.3% of patients, and another component with M = -1.8, SD = 5.1, 34.7%, respectively. For the trimodal model, the component with the largest change (M = -14.3, SD = 6.4) applied to 52% of patients, which differed substantially from the large effect component in Stone et al. (M = -18.8, SD = 5.1) which applied to 7.2%. Secondary/sensitivity analyses arrived at similar conclusions and for patient-reported depression symptoms the best fitting models were unimodal or bimodal.

CONCLUSIONS: This analysis failed to identify the trimodal distribution of response reported in Stone et al. In addition to being difficult to operationalize for regulatory purposes, results from mixture modeling are not sufficiently reliable to replace the more robust approach of comparing mean differences in depression rating scale scores between treatment arms.},
}

@article {pmid40865525,
year = {2025},
author = {McEachin, ZT and Chung, M and Stratton, SA and Han, C and Kim, WJ and Sheth, U and Thomas, EV and Issenberg, E and Kamra, T and Merino, P and Levites, Y and Raj, N and Dammer, EB and Duong, DM and Ping, L and Shantaraman, A and Trautwig, AN and Gadhavi, J and Assefa, E and Gearing, M and Kelly, KM and Roemer, SF and DeTure, M and Asress, S and Kukar, T and Fournier, C and Dickson, DW and Petrucelli, L and Golde, TE and Oskarsson, B and Gendron, TF and Seyfried, NT and Glass, JD},
title = {Molecular impact of antisense oligonucleotide therapy in C9orf72-associated ALS.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2025.07.045},
pmid = {40865525},
issn = {1097-4172},
abstract = {C9orf72-associated amyotrophic lateral sclerosis (c9ALS) is caused by an intronic G4C2 repeat expansion that leads to toxic RNA transcripts and dipeptide repeat proteins (DPRs). A clinical trial using the antisense oligonucleotide (ASO) BIIB078 to target these transcripts was discontinued after failing to provide clinical benefit. Here, we determine the extent of target engagement in the central nervous system (CNS) and elucidate pharmacodynamic cerebrospinal fluid (CSF) biomarkers following treatment. CSF from BIIB078-treated cases showed reduced DPRs and sustained increases in inflammatory biomarkers, including C-C motif chemokine ligand 26 (CCL26). BIIB078 was widely distributed in postmortem CNS tissue; however, DPRs and phosphorylated TDP-43 remained abundant. Proteomic signatures in c9ALS spinal cord were not altered with treatment, although a distinct increase in RNase T2 abundance that correlated with BIIB078 concentration was observed. Thus, despite widespread distribution, BIIB078 did not significantly impact key CNS pathologies, emphasizing the need to identify pharmacodynamic biomarkers that reflect disease-relevant neuropathological changes in response to ASO therapies.},
}

@article {pmid40864790,
year = {2025},
author = {Du, Y and Fan, SS and Wu, H and He, J and He, Y and Meng, XY and Xu, X},
title = {Convergent and Divergent Mitochondrial Pathways as Causal Drivers and Therapeutic Targets in Neurological Disorders.},
journal = {Current issues in molecular biology},
volume = {47},
number = {8},
pages = {},
doi = {10.3390/cimb47080636},
pmid = {40864790},
issn = {1467-3045},
support = {0801059201//the Research Fund for the Doctoral Program of Anhui Medical University/ ; 82303057//National Natural Science Foundation of China/ ; 2023AFB521//Natural Science Foundation of Hubei Province of China/ ; },
abstract = {Mitochondrial dysfunction is implicated across a spectrum of neurological diseases, yet its causal role and mechanistic specificity remain unclear. This study employed a multi-modal integrative analysis of mitochondrial gene expression in Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson's Disease (PD) to address these gaps. We combined machine learning for predictive modeling with genetic causal inference methods (Mendelian Randomization, colocalization, PheWAS), followed by drug enrichment analysis and molecular docking. Our machine learning models, particularly Support Vector Machine and Multi-layer Perceptron, effectively classified these conditions, with MS exhibiting the highest predictability (mean Accuracy: 0.758). Causal inference analyses identified specific gene-disease links; for instance, genetically predicted increased expression of PDK1 was causally associated with an elevated risk for both AD (OR = 1.041) and ALS (OR = 1.037), identifying pyruvate metabolism as a shared vulnerability. In contrast, genes like SLC25A38 emerged as highly predictive specifically for PD. We also observed evidence of potential brain-periphery interaction, such as a bidirectional causal relationship between red blood cell indices and MS risk. Finally, drug enrichment analysis highlighted Celecoxib, and subsequent molecular docking predicted a strong binding affinity to PDK1 (docking score S = -6.522 kcal/mol), generating hypotheses for potential metabolic modulation. Taken together, this study provides a computational hypothesis framework suggesting mitochondrial pathways and targets that warrant future biological validation. This study provides specific, genetically supported evidence for the causal role of mitochondrial pathways in neurological diseases and identifies tangible targets for future therapeutic development.},
}

@article {pmid40864664,
year = {2025},
author = {Popoli, R and Wells, TL and Akay, T},
title = {Unlocking new mechanisms for future ALS therapies: early interventions with cholinergic antagonists reduce neuromuscular decline.},
journal = {Journal of neurophysiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/jn.00306.2025},
pmid = {40864664},
issn = {1522-1598},
support = {2017//ALS Society of Canada (ALS Canada)/ ; 162357//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by motor neuron loss, leading to muscle paralysis and death. C-boutons have been shown to be part of the compensatory mechanism behind delayed symptom onset, and are most active during vigorous exercises, like swimming. When mutant mice with silenced C-boutons perform this exercise, disease progression and behavioral performance drastically improve. Genetic manipulation of C-boutons in human patients remains limited, therefore, we sought to manipulate these synapses using cholinergic antagonists in the presence and absence of exercise in a mouse model of ALS. We demonstrate that atropine and methoctramine administration yield significant improvements in human endpoints, weight maintenance, treadmill performance, and grip strength. Most remarkably, muscle innervation was greatly enhanced at humane endpoints compared to controls, suggesting these drugs provide a protective effect against loss of motor control. We found that methoctramine provided greater benefits in the absence of exercise, hinting at the presence of novel cholinergic mechanisms that can be manipulated in order to preserve motor function. Moreover, we provide evidence that these results are independent of C-boutons, and that methoctramine does not appear to cross the blood-brain barrier. Our results reveal pharmacological mechanisms by which muscle denervation can be reduced, thereby decreasing the rate of disease progression. We have uncovered a promising avenue for improving ALS symptoms by pharmacologically manipulating cholinergic transmission. This mechanism presents as a possible therapy translatable to the clinical setting, which has the potential to prevent the loss of motor control in patients with ALS.},
}

@article {pmid40864229,
year = {2025},
author = {Xu, Y and Raban, MZ and Li, L and Nguyen, AD and Silva, SSM and Huang, G and Arnolda, G and Westbrook, JI and Wabe, N},
title = {Anticholinergic medication use and falls in Australian residential aged care: a retrospective multisite cohort study.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {257},
pmid = {40864229},
issn = {1720-8319},
support = {APP1170898//Australian National Health and Medical Research Council/ ; APP1170898//Australian National Health and Medical Research Council/ ; },
mesh = {Humans ; *Accidental Falls/statistics & numerical data/prevention & control ; *Cholinergic Antagonists/adverse effects/therapeutic use ; Female ; Male ; Aged ; Retrospective Studies ; Aged, 80 and over ; *Homes for the Aged/statistics & numerical data ; Australia ; New South Wales ; },
abstract = {BACKGROUND: Associations between anticholinergic load and falls remain understudied in residential aged care facilities (RACFs).

AIMS: To examine associations between anticholinergic load and falls in the first year after entry to an RACF.

METHODS: We aggregated routinely collected data from 27 RACFs in New South Wales, Australia. Anticholinergic load and falls were repeatedly measured for one year after residents first entered an RACF. Thirteen 28-day review periods were set. Associations between anticholinergic load in a review period and any falls in the next review period were examined, comprising 12 repeated measurements of associations. We included new residents aged ≥ 65 years, who entered an RACF between 1 July 2014 and 2 September 2021. Six scales were used: Anticholinergic Cognitive Burden (ACB), Anticholinergic Drug Scale (ADS), Anticholinergic Loading Scale (ALS), Anticholinergic Risk Scale (ARS), Chew's list, and Clinician-rated Anticholinergic Score (CrAS). We used mixed-effect logistic regression models, adjusting for potential confounders. Facility was used as a cluster variable.

RESULTS: For the 2300 residents (67.7% females), there were steady increases in mean anticholinergic load from the first to the 12th review period. Per one-point higher anticholinergic load was associated with an increased risk of falls, adjusted odds ratios: 1.08 (95% confidence interval[CI] 1.04, 1.12) using ACB, 1.11 (95%CI 1.06, 1.15) using ADS, 1.15 (95%CI 1.10, 1.21) using ALS, 1.10 (95%CI 1.04, 1.17) using ARS, 1.18 (95%CI 1.09, 1.27) using Chew's list, and 1.14 (95%CI 1.10, 1.19) using CrAS.

CONCLUSION: Anticholinergic scales may be useful to inform falls prevention programs for new RACF residents.},
}

Humans
*Accidental Falls/statistics & numerical data/prevention & control
*Cholinergic Antagonists/adverse effects/therapeutic use
Female
Male
Aged
Retrospective Studies
Aged, 80 and over
*Homes for the Aged/statistics & numerical data
Australia
New South Wales

@article {pmid40864161,
year = {2025},
author = {Zhu, Y and Cho, K and Lacin, H and Zhu, Y and DiPaola, JT and Wilson, BA and Patti, G and Skeath, JB},
title = {Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {40864161},
issn = {2050-084X},
support = {NS036570/NS/NINDS NIH HHS/United States ; NS122903/NS/NINDS NIH HHS/United States ; ES2028365/ES/NIEHS NIH HHS/United States ; },
mesh = {Animals ; *Endoplasmic Reticulum/metabolism ; *Neuroglia/metabolism/pathology ; *Lipid Droplets/metabolism ; *Oxidoreductases/metabolism/genetics ; Homeostasis ; *Drosophila Proteins/metabolism/genetics ; Ceramides/metabolism ; *Drosophila melanogaster/genetics ; },
abstract = {Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc), the Drosophila DEGS1 homolog, is expressed primarily in glial cells to promote CNS development by guarding against neurodegeneration. Loss of ifc causes massive dihydroceramide accumulation and severe morphological defects in cortex glia, including endoplasmic reticulum (ER) expansion, failure of neuronal ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream ceramide synthase schlank in glia of ifc mutants rescues ER expansion, suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi knockdown of ifc in glia but not neurons drives neuronal cell death, suggesting that ifc function in glia promotes neuronal survival. Our work identifies glia as the primary site of disease progression in HLD-18 and may inform on juvenile forms of ALS, which also feature elevated dihydroceramide levels.},
}

Animals
*Endoplasmic Reticulum/metabolism
*Neuroglia/metabolism/pathology
*Lipid Droplets/metabolism
*Oxidoreductases/metabolism/genetics
Homeostasis
*Drosophila Proteins/metabolism/genetics
Ceramides/metabolism
*Drosophila melanogaster/genetics

@article {pmid40863128,
year = {2025},
author = {Pawłowska, M and Kruszka, J and Porzych, M and Garbarek, J and Nuszkiewicz, J},
title = {Ketogenic Metabolism in Neurodegenerative Diseases: Mechanisms of Action and Therapeutic Potential.},
journal = {Metabolites},
volume = {15},
number = {8},
pages = {},
pmid = {40863128},
issn = {2218-1989},
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders.},
}