@article {pmid40275359,
year = {2025},
author = {Grima, N and Smith, AN and Shepherd, CE and Henden, L and Zaw, T and Carroll, L and Rowe, DB and Kiernan, MC and Blair, IP and Williams, KL},
title = {Multi-region brain transcriptomic analysis of amyotrophic lateral sclerosis reveals widespread RNA alterations and substantial cerebellum involvement.},
journal = {Molecular neurodegeneration},
volume = {20},
number = {1},
pages = {40},
pmid = {40275359},
issn = {1750-1326},
support = {Ideas Grant 2011120//National Health and Medical Research Council/ ; Investigator Grant 1176913//National Health and Medical Research Council/ ; Angie Cunningham PhD Scholarship and Project Grant-In-Aid Award//FightMND/ ; Discovery Grant//FightMND/ ; Grant-in-Aid//Motor Neurone Disease Research Australia/ ; R28AA012725/AA/NIAAA NIH HHS/United States ; Not applicable//Neuroscience Research Australia/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects the motor neurons, causing progressive muscle weakness and paralysis. While research has focused on understanding pathological mechanisms in the motor cortex and spinal cord, there is growing evidence that extra-motor brain regions may also play a role in the pathogenesis or progression of ALS.

METHODS: We generated 165 sample-matched post-mortem brain transcriptomes from 22 sporadic ALS patients with pTDP-43 pathological staging and 11 non-neurological controls. For each individual, five brain regions underwent mRNA sequencing: motor cortex (pTDP-43 inclusions always present), prefrontal cortex and hippocampus (pTDP-43 inclusions sometimes present), and occipital cortex and cerebellum (pTDP-43 inclusions rarely present). We examined gene expression, cell-type composition, transcript usage (% contribution of a transcript to total gene expression) and alternative splicing, comparing ALS-specific changes between brain regions. We also considered whether post-mortem pTDP-43 pathological stage classification defined ALS subgroups with distinct gene expression profiles.

RESULTS: Significant gene expression changes were observed in ALS cases for all five brain regions, with the cerebellum demonstrating the largest number of total (> 3,000) and unique (60%) differentially expressed genes. Pathway enrichment and predicted activity were largely concordant across brain regions, suggesting that ALS-linked mechanisms, including inflammation, mitochondrial dysfunction and oxidative stress, are also dysregulated in non-motor brain regions. Switches in transcript usage were identified for a small set of genes including increased usage of a POLDIP3 transcript, associated with TDP-43 loss-of-function, in the cerebellum and a XBP1 transcript, indicative of unfolded protein response activity, in the motor cortex. Extensive variation in RNA splicing was identified in the ALS brain, with 26-41% of alternatively spliced genes unique to a given brain region. This included detection of TDP-43-associated cryptic splicing events such as the STMN2 cryptic exon which was shown to have a pTDP-43 pathology-specific expression pattern. Finally, ALS patients with stage 4 pTDP-43 pathology demonstrated distinct gene and protein expression changes in the cerebellum.

CONCLUSIONS: Together our findings highlighted widespread transcriptome alterations in ALS post-mortem brain and showed that, despite the absence of pTDP-43 pathology in the cerebellum, extensive and pTDP-43 pathological stage-specific RNA changes are evident in this brain region.},
}

@article {pmid40273110,
year = {2025},
author = {Souza, AA and Silva, STD and Régis, AMP and Aires, DN and Pondofe, KM and Melo, LP and Valentim, RAM and Lindquist, ARR and Macedo, LRD and Ribeiro, TS},
title = {Muscle strengthening in individuals with Amyotrophic Lateral Sclerosis: a systematic review with meta-analyses.},
journal = {PloS one},
volume = {20},
number = {4},
pages = {e0320788},
doi = {10.1371/journal.pone.0320788},
pmid = {40273110},
issn = {1932-6203},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy ; *Muscle Strength/physiology ; *Resistance Training/methods ; *Exercise Therapy/methods ; },
abstract = {Despite the observed benefits of properly prescribed exercises for people with Amyotrophic Lateral Sclerosis (ALS), the scarcity of studies and lack of consensus on the effects of muscle-strengthening exercises on this population has a negative impact on their rehabilitation. This study aimed to evaluate the effects of muscle-strengthening interventions in individuals with ALS. This systematic review of intervention studies included clinical trials that performed non-respiratory muscle strengthening in people with ALS compared to non-strengthening interventions, usual care, or placebo. Such studies were obtained from the MEDLINE, EMBASE, Cochrane Library, SPORTDiscus, and Physiotherapy Evidence Database databases, with no language or publication date restrictions. The outcomes considered were peripheral muscle strength, functionality, fatigue, and adverse events. The Physiotherapy Evidence Database scale was used to analyze the risk of bias, while the Grading of Recommendations Assessment, Development and Evaluation system was used to evaluate the quality of the evidence. Searches were conducted in October 2023 and eight studies were included, totaling 296 individuals. Seven of the eight studies showed superiority of the experimental intervention over the control, but this was not supported in the meta-analyses. Small sample size and high heterogeneity in the primary studies contributed significantly to the low quality of the evidence. There was no evidence of the superiority of interventions for muscle strengthening compared to interventions not aimed at strengthening, usual care, or placebo in terms of the outcomes analyzed immediately after the intervention. The quality of the evidence ranged from low to very low. Five of the studies evaluated adverse events, without reporting serious events. Interventions for muscle strengthening did not prove to be more effective when compared to the control group in the short term nor seem to produce serious adverse events. The low quality of the evidence indicates the need for studies with greater methodological rigor in this population, to more assertively assess the impacts of this intervention over the short, medium, and long term.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/therapy
*Muscle Strength/physiology
*Resistance Training/methods
*Exercise Therapy/methods

@article {pmid40272376,
year = {2025},
author = {Nguyen, THV and Ferron, F and Murakami, K},
title = {Neurotoxic Implications of Human Coronaviruses in Neurodegenerative Diseases: A Perspective from Amyloid Aggregation.},
journal = {ACS chemical biology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschembio.5c00153},
pmid = {40272376},
issn = {1554-8937},
abstract = {Human coronaviruses (HCoVs) include seven species: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1, and SARS-CoV-2. The last three, classified as Betacoronaviruses, are highly transmissible and have caused severe pandemics. HCoV infections primarily affect the respiratory system, leading to symptoms such as dry cough, fever, and breath shortness, which can progress to acute respiratory failure and death. Beyond respiratory effects, increasing evidence links HCoVs to neurological dysfunction. However, distinguishing direct neural complications from preexisting disorders, particularly in the elderly, remains challenging. This study examines the association between HCoVs and neurodegenerative diseases like Alzheimer disease, Parkinson disease, Lewy body dementia, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. It also presents the long-term neurological effects of HCoV infections and their differential impact across age groups and sexes. A key aspect of this study is the investigation of the sequence and structural similarities between amyloidogenic and HCoV spike proteins, which can provide insights into potential neuropathomechanisms.},
}

@article {pmid40271431,
year = {2025},
author = {Rana, A and Katiyar, A and Arun, A and Berrios, JN and Kumar, G},
title = {Natural sulfur compounds in mental health and neurological disorders: insights from observational and intervention studies.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1534000},
doi = {10.3389/fnut.2025.1534000},
pmid = {40271431},
issn = {2296-861X},
abstract = {Over the years, the global disease burden of neurological disorders (NDs) and mental disorders (MDs) has significantly increased, making them one of the most critical concerns and challenges to human health. In pursuit of novel therapies against MD and ND, there has been a growing focus on nutrition and health. Dietary sulfur, primarily derived from various natural sources, plays a crucial role in numerous physiological processes, including brain function. This review offers an overview of the chemical composition of several natural sources of the sulfur-rich substances such as isothiocyanates, sulforaphane, glutathione, taurine, sulfated polysaccharides, allyl sulfides, and sulfur-containing amino acids, all of which have neuroprotective properties. A multitude of studies have documented that consuming foods that are high in sulfur enhances brain function by improving cognitive parameters and reduces the severity of neuropathology by exhibiting antioxidant and anti-inflammatory properties at the molecular level. In addition, the growing role of natural sulfur compounds in repairing endothelial dysfunction, compromising blood-brain barrier and improving cerebral blood flow, are documented here. Furthermore, this review covers the encouraging results of supplementing sulfur-rich diets in many animal models and clinical investigations, along with their molecular targets in MD, such as schizophrenia, depression, anxiety, bipolar disorder, and autism spectrum disorder, and ND, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). The prospects of natural sulfur compounds show great promise as they have potential applications in nutraceuticals, medicines, and functional foods to enhance brain function and prevent diseases. However, additional research is required to clarify the mechanisms by which it works, enhance its bioavailability, and evaluate its long-term safety for broad use.},
}

@article {pmid40271315,
year = {2025},
author = {Honda, N and Watanabe, Y and Honda, H and Uemoto, M and Fukuhara, H and Hanajima, R},
title = {Implications of Mutant SOD1 on RNA Processing and Interferon Responses in Amyotrophic Lateral Sclerosis: Omics Data Analysis.},
journal = {Cureus},
volume = {17},
number = {3},
pages = {e81045},
doi = {10.7759/cureus.81045},
pmid = {40271315},
issn = {2168-8184},
abstract = {INTRODUCTION: Cytoplasmic inclusions are observed in motor neurons in amyotrophic lateral sclerosis (ALS) associated with the Cu/Zn superoxide dismutase mutation (mtSOD1). Although these inclusions are a hallmark of the disorder, degeneration is not necessarily initiated in the cytoplasm, nor are these structures the culprit of ALS. The nucleus stores genetic material and acts as the cell's control center, and a small fraction of mtSOD1 is reported to be distributed in the nucleus. We hypothesized that mtSOD1 in the nucleus contributes to motor neuron degeneration.

METHODS: We explored the roles of mtSOD1 in relation to nuclear proteins, chromosomal DNA, and mRNA expression. An immortalized cell line derived from a transgenic ALS mouse model expressing mtSOD1-L126delTT with a FLAG was used for stable immunoprecipitation of mtSOD1-binding molecules using shotgun proteomics and chromatin immunoprecipitation-sequencing (ChIP-seq). We also examined mRNA expression by silencing whole SOD1 (innate mouse Sod1 and mtSOD1) or mtSOD1 alone and compared these patterns against those in non-silenced counterparts.

RESULTS: We identified 392 mtSOD1-interacting proteins in the nucleus. Gene ontology (GO) revealed these proteins to be enriched for "mRNA processing." Notably, more than 11% of mtSOD1-interacting proteins were expressed concurrently with previously reported wild-type TAR DNA-binding protein 43 (TDP-43)-interacting proteins. ChIP-seq revealed that mtSOD1-interacting DNA portions showed a preference for zinc finger protein-binding motifs. GO analysis of the ChIP-seq data revealed that "mRNA processing" was again enriched among the genes harboring mtSOD1-binding domains. RNA expression analyses revealed that the presence of mouse Sod1 and mtSOD1 induced the overexpression of molecules related to "type 1 IFN responses."

CONCLUSIONS: We revealed that mtSOD1 interacted with nuclear proteins and specific DNA segments and that RNA expression was notably altered when mouse Sod1 and mtSOD1 were silenced. These interactions could play a pivotal role in motor neuron degeneration.},
}

@article {pmid40271071,
year = {2025},
author = {Luo, H and Wei, S and Fu, S and Han, L},
title = {Role of Achyranthes aspera in neurodegenerative diseases: current evidence and future directions.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1511011},
doi = {10.3389/fphar.2025.1511011},
pmid = {40271071},
issn = {1663-9812},
abstract = {Neurodegenerative diseases are caused by the progressive degeneration of neurons and/or their myelin sheaths, ultimately leading to cognitive and motor dysfunction. Due to their complex pathogenesis and the limited efficacy of therapeutic drugs, these diseases have attracted significant attention. Achyranthes aspera, belongs to family Amaranthaceae, has been extensively used in the traditional and folk medicines for the treatment of various ailments. Modern research has revealed that Achyranthes aspera possesses various pharmacological effects, including cardiocerebrovascular protection, immune regulation, antioxidation, and anti-aging. Furthermore, the neuroprotective effects of Achyranthes aspera have been confirmed by numerous scientific studies. This review focuses on the primary pharmacological effects and mechanisms of Achyranthes aspera in the prevention and treatment of neurodegenerative diseases, as well as their potential application prospects. This review aims to provide insights into the potential clinical applications and research directions of Achyranthes aspera in neurodegenerative diseases.},
}

@article {pmid40268233,
year = {2025},
author = {Basak, B and Holzbaur, ELF},
title = {Mitophagy in Neurons: Mechanisms Regulating Mitochondrial Turnover and Neuronal Homeostasis.},
journal = {Journal of molecular biology},
volume = {},
number = {},
pages = {169161},
doi = {10.1016/j.jmb.2025.169161},
pmid = {40268233},
issn = {1089-8638},
abstract = {Mitochondrial quality control is instrumental in regulating neuronal health and survival. The receptor-mediated clearance of damaged mitochondria by autophagy, known as mitophagy, plays a key role in controlling mitochondrial homeostasis. Mutations in genes that regulate mitophagy are causative for familial forms of neurological disorders including Parkinson's disease (PD) and Amyotrophic lateral sclerosis(ALS). PINK1/Parkin-dependent mitophagy is the best studied mitophagy pathway, while more recent work has brought to light additional mitochondrial quality control mechanisms that operate either in parallel to or independent of PINK1/Parkin mitophagy. Here, we discuss our current understanding of mitophagy mechanisms operating in neurons to govern mitochondrial homeostasis. We also summarize progress in our understanding of the links between mitophagic dysfunction and neurodegeneration and highlight the potential for therapeutic interventions to maintain mitochondrial health and neuronal function.},
}

@article {pmid40267658,
year = {2025},
author = {Orsucci, D and Vista, M and Santorelli, FM},
title = {Conversational AI in neurogenetics. The example of FUS gene.},
journal = {Journal of the neurological sciences},
volume = {473},
number = {},
pages = {123511},
doi = {10.1016/j.jns.2025.123511},
pmid = {40267658},
issn = {1878-5883},
}

@article {pmid40267619,
year = {2025},
author = {Garnés-Camarena, O and Mahíllo-Fernández, I and Martínez-Ulloa, P and Mandeville, R and Lorenzo, O and Stashuk, DW},
title = {Towards early diagnosis of amyotrophic lateral sclerosis using near fibre EMG.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {174},
number = {},
pages = {114-122},
doi = {10.1016/j.clinph.2025.04.006},
pmid = {40267619},
issn = {1872-8952},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons and diagnosis is usually delayed several months. The continuous denervation and reinnervation associated with ALS are manifest in EMG signals as changes in motor unit potential (MUP) size, temporal dispersion and instability. Near Fibre EMG is a novel method to assess early changes in MUP temporal dispersion and instability using routinely recorded EMG signals in a semi-automated manner.

METHODS: Near Fibre EMG values from 2318 MUs, retrospectively sampled at the time of ALS diagnosis, from 96 muscles of 15 patients were compared with values from 3954 MUs sampled from 109 muscles of 84 reference subjects.

RESULTS: 30.1% and 46.1% of ALS MUs had MUPs with increased complexity or instability, respectively, and 17.4% had both. The potential importance and heightened sensitivity of NFEMG was highlighted when analyzing normal-sized motor units; as many as 24% of the normal-sized MUPs actually had significant instability, while 14% had increased complexity, and 7.4% had both.

CONCLUSIONS: Near Fibre EMG can characterize motor unit electrophysiological status and hence help quantify the degree, and course of denervation and reinnervation.

SIGNIFICANCE: Near-Fiber EMG offers the potential to facilitate earlier ALS diagnosis, which, as promising therapies become available, can be consequential.},
}

@article {pmid40267236,
year = {2025},
author = {Zhong, H and Zhu, J and Liu, S and Zhou, D and Long, Q and Wu, C and Zhao, B and Cheng, C and Yang, Y and Wu, Q and Wu, Y and Li, C and Wang, Z and Wu, J and Guo, X and Zhi, D and Deng, Y and Wu, L},
title = {Linking DNA methylation in brain regions to Alzheimer's disease risk: a Mendelian randomization study.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddaf053},
pmid = {40267236},
issn = {1460-2083},
support = {//University of Hawai'i Cancer Center/ ; },
abstract = {AIM: DNA methylation in brain regions represents a potential mechanism linking genetic variation to Alzheimer's disease (ad) risk, yet most studies have focused on blood-derived methylation markers. In this study, we conducted a systematic Mendelian randomization (MR) study to evaluate associations between predicted brain region-specific DNA methylation levels and ad risk, using methylation quantitative trait loci (mQTL) as genetic instruments.

METHODS: We analyzed mQTLs from five human brain regions: cerebellum (CRBLM), frontal cortex (FCTX), causal pons (PONS), and temporal cortex (TCTX) from 600 individuals in Gibbs et al's study, as well as mQTLs from dorsolateral prefrontal cortex (DLPFC) of 543 participants in the Religious Orders Study and the Rush Memory and Aging Project (ROSMAP). In our MR analyses, we integrated these mQTLs with single nucleotide polymorphisms (SNP)-ad risk summary statistics derived from 85 934 ad-related cases and 401 577 normal controls.

RESULTS: Among 62 554 cytosine-guanine dinucleotide (CpG) sites, we identified 597 CpG sites (CpGs) significantly associated with ad risk (false discovery rate (FDR) < 0.05). Of these, 289 were confirmed through colocalization and summary-based MR (SMR) analyses, including one CpG site in CRBLM, 285 in DLPFC, one in FCTX, two in PONS, and one in TCTX. By integrating gene expression data, we identified 19 CpG sites with consistent associations across methylation levels, expression of eight target genes, and ad risk, including novel regulatory mechanisms involving RITA1's modulation of cg11558705 and PCGF3's regulation of cg10009224.

CONCLUSION: Our findings highlight brain region-specific DNA methylation as a mediator of genetic risk for ad, offering insights into ad pathogenesis and identifying potential therapeutic targets.},
}

@article {pmid40267187,
year = {2025},
author = {Guillaud, L and Garanzini, A and Zakhia, S and De la Fuente, S and Dimitrov, D and Boerner, S and Terenzio, M},
title = {Loss of intracellular ATP affects axoplasmic viscosity and pathological protein aggregation in mammalian neurons.},
journal = {Science advances},
volume = {11},
number = {17},
pages = {eadq6077},
doi = {10.1126/sciadv.adq6077},
pmid = {40267187},
issn = {2375-2548},
mesh = {*Adenosine Triphosphate/metabolism ; Humans ; Animals ; *Protein Aggregation, Pathological/metabolism/pathology ; Mice ; *Neurons/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; *Axons/metabolism ; Viscosity ; Mitochondria/metabolism ; Protein Aggregates ; Parkinson Disease/metabolism/pathology ; DNA-Binding Proteins/metabolism ; Alzheimer Disease/metabolism/pathology ; },
abstract = {Neurodegenerative diseases display synaptic deficits, mitochondrial defects, and protein aggregation. We show that intracellular adenosine triphosphate (ATP) regulates axoplasmic viscosity and protein aggregation in mammalian neurons. Decreased intracellular ATP upon mitochondrial inhibition leads to axoterminal cytosol, synaptic vesicles, and active zone component condensation, modulating the functional organization of mouse glutamatergic synapses. Proteins involved in the pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) condensed and underwent ATP-dependent liquid phase separation in vitro. Human inducible pluripotent stem cell-derived neurons from patients with PD and ALS displayed reduced axoplasmic fluidity and decreased intracellular ATP. Last, nicotinamide mononucleotide treatment successfully rescued intracellular ATP levels and axoplasmic viscosity in neurons from patients with PD and ALS and reduced TAR DNA-binding protein 43 (TDP-43) aggregation in human motor neurons derived from a patient with ALS. Thus, our data suggest that the hydrotropic activity of ATP contributes to the regulation of neuronal homeostasis under both physiological and pathological conditions.},
}

*Adenosine Triphosphate/metabolism
Humans
Animals
*Protein Aggregation, Pathological/metabolism/pathology
Mice
*Neurons/metabolism
Induced Pluripotent Stem Cells/metabolism
Amyotrophic Lateral Sclerosis/metabolism/pathology
*Axons/metabolism
Viscosity
Mitochondria/metabolism
Protein Aggregates
Parkinson Disease/metabolism/pathology
DNA-Binding Proteins/metabolism
Alzheimer Disease/metabolism/pathology

@article {pmid40265300,
year = {2025},
author = {Xu, IQ and Guo, L and Xu, J and Setiawan, S and Deng, X and Lo, YL and Chai, JYH and Simmons, Z and Ramasamy, S and Yeo, CJJ},
title = {Predictive Analysis of Amyotrophic Lateral Sclerosis Progression and Mortality in a Clinic Cohort From Singapore.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.28416},
pmid = {40265300},
issn = {1097-4598},
support = {C210112024//Agency for Science, Technology and Research/ ; IRNMR21CPGJJ//National Neuroscience Institute/ ; },
abstract = {INTRODUCTION: There is currently no comprehensive Amyotrophic Lateral Sclerosis (ALS) patient database in Singapore comparable to those available in Europe and the United States. We established the Singapore ALS registry (SingALS) to draw meaningful inferences about the ALS population in Singapore through developing statistical and machine learning-based predictive models.

METHODS: The SingALS registry was established through the retrospective collection of demographic, clinical, and laboratory data from 72 ALS patients at Tan Tock Seng Hospital (TTSH) and combining it with demographic and clinical data from 71 patients at Singapore General Hospital (SGH). The SingALS was compared against international ALS registries. Using comparative studies including survival and temporal feature analysis, we identified key factors influencing ALS survival and developed a machine learning model to predict survival outcomes.

RESULTS: Compared to Caucasian-dominant registries, such as the German Swabia registry, SingALS patients had longer average survival (50.51 vs. 31.0 months), younger age of onset (56.18 vs. 66.6 years), and lower bulbar onset prevalence (20.98% vs. 34.10%). Singaporean males had poorer outcomes compared to females, with a hazard ratio (HR) of 3.12 (p = 0.008). Patients who died within 24 months had an earlier need for being bedbound (p < 0.004), percutaneous endoscopic gastrostomy (PEG) insertion (p = 0.004) and non-invasive ventilation (NIV) (p < 0.001). Machine learning and statistical analysis indicated that a steeper ALSFRS-R slope, higher alkaline phosphatase (ALP), white blood cell (WBC), absolute neutrophil counts, and creatinine levels are associated with worse mortality.

DISCUSSION: We developed a comprehensive Singaporean ALS registry and identified key factors influencing survival.},
}

@article {pmid40265276,
year = {2025},
author = {Mendonça, IP and Peixoto, CA},
title = {The Double-Edged Sword: The Complex Function of Enteric Glial Cells in Neurodegenerative Diseases.},
journal = {Journal of neurochemistry},
volume = {169},
number = {4},
pages = {e70069},
doi = {10.1111/jnc.70069},
pmid = {40265276},
issn = {1471-4159},
support = {CNPq;#301891/2022-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; IAM-PROEP# 005-FIO-22//Instituto Aggeu Magalhães/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/pathology/metabolism ; *Neuroglia/metabolism/pathology/physiology ; Animals ; *Enteric Nervous System/pathology/metabolism ; },
abstract = {Over the past two decades, a growing number of studies have been conducted on the role of bidirectional communication through the gut-brain axis in the development of neurodegenerative diseases. These studies were driven by the curious fact that all of these diseases present varying degrees of intestinal involvement included in their wide range of symptoms. A population of cells belonging to the ENS, called enteric glial cells (EGCs), appears to actively participate in this communication between the intestine and the brain, but acting in a dualistic manner, sometimes in reactive gliosis releasing inflammatory mediators, sometimes promoting homeostasis and resilience in the face of inflammatory injuries. To date, the intracellular mechanisms that define the transcriptional profile expressed in EGCs in each situation have not yet been elucidated. This review proposes a discussion on: (1) the complex role of distinct phenotypes of enteric glial cells involved in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and multiple sclerosis (MS); and (2) innovative strategies such as IDO/TDO inhibitors, Brazil nuts, caffeic acid, polyphenols, among others, that act on EGCs and have the potential to treat neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/pathology/metabolism
*Neuroglia/metabolism/pathology/physiology
Animals
*Enteric Nervous System/pathology/metabolism

@article {pmid40264898,
year = {2024},
author = {Kumar, J and Varela-Ramirez, A and Narayan, M},
title = {Development of novel carbon-based biomedical platforms for intervention in xenotoxicant-induced Parkinson's disease onset.},
journal = {BMEmat},
volume = {2},
number = {4},
pages = {},
pmid = {40264898},
issn = {2751-7446},
abstract = {Chronic exposure to herbicides, weedicides, and pesticides is associated with the onset and progress of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we have investigated whether quinic- and chlorogenic-acid-derived Carbon Quantum Dots (QACQDs and ChACQDs, respectively) protect against a (pesticide) paraquat-insult model of PD. Our results indicated that both types of CQDs intervened in the soluble-to-toxic transformation of the amyloid-forming model protein Hen Egg White Lysozyme (HEWL). Furthermore, QACQDs and ChACQDs demonstrated antioxidant activity while remaining biocompatible in a human neuroblastoma-derived cell line (SH-SY5Y) up to 5 mg/ml and protected the cell line from the environmental neurotoxicant (paraquat). Importantly, both CQDs were found to protect dopaminergic neuronal ablation in a paraquat model of Parkinson's disease using the nematode C. elegans. Our results are significant because both plant-derived organic acids cross the blood-brain barrier, making them attractive for developing CQD architectures. Furthermore, since the synthesis of these CQDs was performed using green chemistry methods from precursor acids that cross the BBB, these engineered bionanomaterial platforms are tantalizing candidates for preventing neurodegenerative disorders associated with exposure to environmental neurotoxicants.},
}

@article {pmid40263468,
year = {2025},
author = {Su, Y and Schwartz, M and Fayad, I and García, M and Zavala, MA and Tijerín-Triviño, J and Astigarraga, J and Cruz-Alonso, V and Liu, S and Zhang, X and Chen, S and Ritter, F and Besic, N and d'Aspremont, A and Ciais, P},
title = {Canopy height and biomass distribution across the forests of Iberian Peninsula.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {678},
pmid = {40263468},
issn = {2052-4463},
support = {ANR-22-FAI1-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-22-FAI1-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-22-FAI1-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-22-FAI1-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; },
abstract = {Accurate mapping of vegetation canopy height and biomass distribution is essential for effective forest monitoring, climate change mitigation, and sustainable forestry. Here we present high-resolution remote sensing-based canopy height (10 m resolution) and above ground biomass (AGB, 50 m resolution) maps for the forests of the Iberian Peninsula from 2017 to 2021, using a deep learning framework that integrates Sentinel-1, Sentinel-2, and LiDAR data. Two UNET models were developed: one trained on Airborne Laser Scanning (ALS) data (MAE: 1.22 m), while another using Global Ecosystem Dynamics Investigation (GEDI) footprints (MAE: 3.24 m). External validation with 6,308 Spanish National Forest Inventory (NFI) plots (2017-2019) confirmed canopy height reliability, showing MAEs of 2-3 m in tree-covered areas. AGB estimates were obtained through Random Forest models that linked UNET derived height predictions to NFI AGB data, achieves an MAE of ~29 Mg/ha. The creation of high-resolution maps of canopy height and biomass across various forest landscapes in the Iberian Peninsula provides a valuable new tool for environmental researchers, policy makers, and forest management professionals, offering detailed insights that can inform conservation strategies, carbon sequestration efforts, and sustainable forest management practices.},
}

@article {pmid40262868,
year = {2025},
author = {Shi, Y and Wu, Z and Cheng, R and Zhang, L and Guo, X and Li, X and Bi, Y},
title = {The Trp-574-Leu mutations together with enhanced metabolism contribute to cross-resistance to ALS inhibiting herbicides in Fimbristylis littoralis.},
journal = {Pesticide biochemistry and physiology},
volume = {210},
number = {},
pages = {106385},
doi = {10.1016/j.pestbp.2025.106385},
pmid = {40262868},
issn = {1095-9939},
abstract = {Fimbristylis littoralis Gaudich., an important weed in Chinese paddy fields, has caused significant yield losses in rice and other crops. Acetolactate synthase (ALS) inhibitors, such as halosulfuron-methyl, are widely used for weed control. This study identified a highly resistant population (R23-1) of F. littoralis to halosulfuron-methyl, with an exceptionally high resistance index (RI) of 3441.66. The resistant mechanisms of F. littoralis to ALS inhibitors have not been reported previously. We employed a comprehensive approach to address this, including whole-plant bioassay, ALS target gene sequencing, molecular docking, synergistic tests with metabolic enzyme inhibitors, glutathione S-transferases (GSTs) activity assays, and cross-resistance testing. The results revealed the first report of a Trp-574-Leu mutation in the ALS gene of the R23-1 population, which significantly increased binding energy, as shown by molecular docking analysis. Synergistic tests demonstrated that the cytochrome P450 monooxygenase (P450) inhibitor piperonyl butoxide (PBO) and the GSTs inhibitor 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl) markedly enhanced the sensitivity of the R23-1 population to halosulfuron-methyl, with synergistic ratios of 4.11 and 8.15, respectively, while malathion had no effect. GST activity decreased in both populations after halosulfuron-methyl treatment, with the R23-1 population consistently showing significantly higher levels, peaking on day five. Furthermore, the R23-1 population demonstrated cross-resistance to multiple ALS inhibitors. These findings provide novel insights into the resistance mechanisms of F. littoralis and lay a theoretical foundation for developing effective strategies to mitigate or delay the evolution of resistance.},
}

@article {pmid40262704,
year = {2025},
author = {Kim, HB and Ehsan, MF and Alshawabkeh, AN and Kim, JG},
title = {Electrochemical activation of alum sludge for the adsorption of lead (Pb(II)) and arsenic (As): Mechanistic insights and machine learning (ML) analysis.},
journal = {Bioresource technology},
volume = {},
number = {},
pages = {132563},
doi = {10.1016/j.biortech.2025.132563},
pmid = {40262704},
issn = {1873-2976},
abstract = {Alum sludge (AlS) has emerged as an effective adsorbent for anionic contaminants, with traditional activation methods like acid/base treatments and calcination employed to enhance its adsorption capacity. However, these approaches encounter significant drawbacks, including excessive waste generation, structural degradation, and limited efficacy for cationic contaminants. To overcome these challenges, this study proposes electrochemical activation as a sustainable method to enhance alum sludge adsorption performance by generating oxygen-containing functional groups (O-FGs) on its surface. In particular, cathodic activated AlS (E-AlS) leads to the formation of hydroxyl (-OH) and carboxyl (-COOH) groups, which served as key active sites for Pb(II) adsorption through complexation mechanisms. E-AlS effectively removed both Pb(II) and As within 4 h, showcasing its dual functionality for cationic and anionic contaminants. While HCl- and KOH-activated AlS also achieved 100 % Pb(II) removal, they caused substantial aluminum (Al) leaching, exceeding 1,000 mg/L, due to structural instability. In contrast, E-AlS minimized Al leaching, preserved structural integrity, and exhibited a 6.5-fold higher Pb(II) adsorption capacity than raw AlS. X-ray photoelectron spectroscopy (XPS) and machine learning (ML) validated the enhanced adsorption performance of E-AlS. These findings highlight electrochemical activation as a cost-effective and environmentally friendly remediation.},
}

@article {pmid40262277,
year = {2025},
author = {Turner, N and Palmer, J and Faull, C and Davidson, S and Turner, MR and Wilson, E},
title = {Tracheostomy ventilation in ALS: healthcare practitioner perspectives on quality of life and implications for decision-making.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2025.2495014},
pmid = {40262277},
issn = {2167-9223},
abstract = {Objectives: This qualitative study aimed to increase understanding of how healthcare practitioners (HCPs) perceive quality of life for people with ALS who use tracheostomy ventilation (TV) and the extent to which such views inform discussions regarding future treatment and care. Methods: A thematic analysis was applied to data derived from online semi-structured interviews with a professionally diverse group of 24 HCPs with experience of supporting people with ALS to use TV. Results: Four main themes relating to TV use emerged: i) Positive benefits; ii) Risks and challenges; iii) Factors influencing HCP perspectives; iv) Concepts informing HCP discussions. HCPs acknowledged that TV has the potential to extend life but were concerned with prolonging a serious decline in physical and cognitive functioning. HCPs tried to identify the 'tipping point' between quantity and quality of life for the individual and their family, taking into account the likelihood of a higher burden of care. HCPs drew on prior experience to assess anticipated quality of life, yet most HCPs in the UK have limited experience of TV for this group. HCPs also drew on principles of person-centered care, patient autonomy and value for money to guide their approach to discussing TV. Conclusions: HCP experience of positive outcomes of TV can foster a more proactive approach to initiating conversations about its potential use. Sharing best practice and improving guidance for HCPs may support early and on-going future care planning and enable people with ALS to make choices which are informed and in their best interests.},
}

@article {pmid40261626,
year = {2025},
author = {Lum, JS and Brown, ML and Suters, SC and Yerbury, JJ and McAlary, L},
title = {In-Gel Zymography of Amyotrophic Lateral Sclerosis-Associated Variants of Superoxide Dismutase-1.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2918},
number = {},
pages = {221-228},
pmid = {40261626},
issn = {1940-6029},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/enzymology/metabolism ; *Superoxide Dismutase-1/genetics/metabolism ; Humans ; *Enzyme Assays/methods ; *Electrophoresis, Polyacrylamide Gel/methods ; },
abstract = {In-gel zymography allows the separation of protein via electrophoresis and subsequent measurement of enzymatic activity of enzymes from biological mixtures. The antioxidant enzyme superoxide dismutase 1 (SOD1) is an important cytosolic oxygen radical scavenging enzyme that has been implicated in a range of pathologies, including cancer, metabolic and neurodegenerative diseases, most notably amyotrophic lateral sclerosis (ALS). Here, we describe a method to detect and compare SOD1 activity from both cell and tissue samples. This method can be utilized to compare differences between ALS-associated SOD1 genetic variants and pharmacologically treated biological samples.},
}

*Amyotrophic Lateral Sclerosis/genetics/enzymology/metabolism
*Superoxide Dismutase-1/genetics/metabolism
Humans
*Enzyme Assays/methods
*Electrophoresis, Polyacrylamide Gel/methods

@article {pmid40261116,
year = {2025},
author = {Shneider, NA and Nesta, AV and Rifai, OM and Yasek, J and Elyaman, W and Aziz-Zaman, S and Lyu, MA and Levy, SHS and Hoover, BN and Vlad, G and Huang, M and Zeng, K and Sadeghi, T and Reddy, A and Flowers, CR and Parmar, S},
title = {Clinical Safety and Preliminary Efficacy of Regulatory T Cells for ALS.},
journal = {NEJM evidence},
volume = {4},
number = {5},
pages = {EVIDoa2400249},
doi = {10.1056/EVIDoa2400249},
pmid = {40261116},
issn = {2766-5526},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; Middle Aged ; *T-Lymphocytes, Regulatory/transplantation ; Female ; Male ; Aged ; Adult ; Biomarkers/blood ; Treatment Outcome ; Neurofilament Proteins/blood ; },
abstract = {BACKGROUND: Peripheral and neuroinflammation have been previously associated with progression in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease involving progressive loss of motor neurons. We hypothesize that regulatory T cell (Treg) therapy can resolve inflammation and preserve function in those patients with ALS.

METHODS: Participants with ALS received infusions of a fixed dose (100×10[6] cells) of umbilical cord blood-derived, allogeneic, nonhuman leukocyte antigen-matched, cryopreserved Treg product (TREG), administered as four weekly infusions followed by six monthly infusions. No lymphodepletion, immunosuppression, or interleukin 2 was administered. The primary outcome was dose-limiting toxicity, including infusion reaction within 24 hours (as graded by National Cancer Institute - Common Terminology Criteria for Adverse Events, Version 4.0) and/or regimen-related death, or grade 3 or 4 cytokine release syndrome within 14 days postinfusion. We measured clinical response using the Revised ALS Functional Rating Scale (ALSFRS-R; range 0 to 48, with lower numbers indicating lower functional ability). Exploratory analyses measured serum and plasma neurofilament light (NfL) and inflammatory biomarkers.

RESULTS: Six participants with a median age of 48.5 years (range 27 to 66 years) and baseline ALSFRS-R score of 31.5 (range 23 to 43) were treated with a median of 11 (range 6 to 22) TREG infusions in an ambulatory setting. No dose-limiting toxicity was observed. In participants with sufficient data points (n=4), the mean ALSFRS-R slope of decline was -1.66±1.03 points/month before treatment, -0.41±0.45/month during treatment, and -0.60±0.59/month posttreatment. Biomarkers including NfL and inflammatory markers MIP-1δ (macrophage inflammatory protein-1 delta), CTACK (cutaneous T cell-attracting chemokine), and GROα (growth-regulated oncogene alpha) exhibited different relationships with ALSFRS-R score between participants.

CONCLUSIONS: This study demonstrates the preliminary safety of "off-the-shelf", allogeneic Treg-cell therapy.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy
Middle Aged
*T-Lymphocytes, Regulatory/transplantation
Female
Male
Aged
Adult
Biomarkers/blood
Treatment Outcome
Neurofilament Proteins/blood

@article {pmid40261114,
year = {2025},
author = {Abati, E},
title = {Regulatory T Cell-Based Therapies - A New Piece of the ALS Therapeutic Puzzle?.},
journal = {NEJM evidence},
volume = {4},
number = {5},
pages = {EVIDe2500078},
doi = {10.1056/EVIDe2500078},
pmid = {40261114},
issn = {2766-5526},
}

@article {pmid40260525,
year = {2025},
author = {Ganapule, A and Garg, D and Agarwal, A and Gupta, A and Rajan, R and Desai, S and Chandarana, M and Sidharth, S and Tripathi, M and Garg, A and Radhakrishnan, DM and Srivastava, AK},
title = {The Expanding Spectrum of Anti-IgLON5 Disease: A Case Series from an Indian Cohort.},
journal = {Annals of Indian Academy of Neurology},
volume = {},
number = {},
pages = {},
doi = {10.4103/aian.aian_1073_24},
pmid = {40260525},
issn = {0972-2327},
abstract = {Anti-IgLON5 disease is an evolving entity that lies at the confluence of autoimmunity and neurodegeneration. Reports from India remain sparse. In this series, we describe seven Indian patients with anti-IgLON5-related disease. Patients presented across the fifth to eighth decades with a mean duration of illness of 16 months. All had movement disorders, which included gait ataxia, parkinsonism, and chorea. Six patients had sleep disturbances. Five had a frontal dysexecutive dementia phenotype. Two had epilepsy. Bulbar involvement was present in four, and one had amyotrophic lateral sclerosis (ALS)-like features. Magnetic resonance imaging was abnormal in two cases. Positron emission tomography of the brain also contributed to diagnosis. Combination immunotherapies were used in most of the patients, with three showing a sustained response and two deaths reported due to sepsis-related complications. It is important to recognize the increasing spectrum of IgLON5-related disease to enable timely initiation of immunotherapy before marked degeneration occurs.},
}

@article {pmid40260387,
year = {2025},
author = {Guo, N and Huang, W and Huang, J and Liu, Y and Zhu, K and Gao, W},
title = {Global research trends in biomarkers, therapeutic targets, and drugs for amyotrophic lateral sclerosis: a bibliometric and visualization analysis.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1588968},
pmid = {40260387},
issn = {1663-9812},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons, marked by complex pathological mechanisms and a lack of effective treatments. Despite substantial global research efforts, no comprehensive bibliometric analysis has systematically mapped the evolution of ALS biomarkers, therapeutic targets, and pharmacological advancements.

METHODS: This study, based on 4,250 publications retrieved from the Web of Science Core Collection (2005-2025), employs bibliometric tools such as CiteSpace and VOSviewer to conduct the first multidimensional analysis of global trends in ALS biomarkers, therapeutic targets, and drug research.

RESULTS: The results revealed contributions from 20,168 authors across 92 countries, with annual publications growing at an average rate of 16.5%. The United States dominated research output, accounting for 34.07% (n=1,448, TLCS=7,100), while the United Kingdom achieved the highest research impact with an average of 68 citations per article. Leading institutions, including the University of Oxford and the University of Milan, consistently produced high-impact studies. Pioneering scholars such as Turner MR and Kiernan MC made significant contributions to advancing therapeutic targets and drug discovery. The interdisciplinary integration of molecular biology and genetics emerged as a core driver of progress in ALS research. Neurofilament light chain (NfL), antisense oligonucleotide (ASO) drugs, transcranial magnetic stimulation (TMS), oxygen free radicals (oxidative stress), and gene therapy have consistently remained central research focuses in the ALS therapeutic field. Looking ahead, stem cell therapy, blood-brain barrier (BBB) penetration technologies, and skeletal muscle targeting are poised to emerge as prominent research directions.

CONCLUSION: The United States dominates ALS research productivity, whereas the United Kingdom demonstrates superior citation influence. Despite China's substantial publication volume, its limited citation impact underscores the necessity for enhanced methodological rigor and strategic international collaboration. Current research priorities encompass NfL, TMS, and ASO therapies, with emerging innovations in stem cell therapy, BBB penetration technologies and skeletal muscle targeting showing therapeutic promise. Future directions should prioritize biomarker standardization, optimization of drug delivery systems, and Clinical Translation.},
}

@article {pmid40259632,
year = {2025},
author = {García-Casanova, PH and Pérez-Martínez, P and Sevilla, T and Doménech, R and León, M and Vázquez-Costa, JF},
title = {In Response to "Homogeneous ALS Cohorts in Terms of Etiology, Onset Type and Vaccination Status Are Required to Assess the Outcome of Their COVID Infection".},
journal = {European journal of neurology},
volume = {32},
number = {4},
pages = {e70162},
doi = {10.1111/ene.70162},
pmid = {40259632},
issn = {1468-1331},
}

@article {pmid40259624,
year = {2025},
author = {Finsterer, J},
title = {Homogeneous ALS Cohorts in Terms of Etiology, onset type, and Vaccination Status Are Required to Assess the Outcome of Their COVID Infection.},
journal = {European journal of neurology},
volume = {32},
number = {4},
pages = {e70161},
doi = {10.1111/ene.70161},
pmid = {40259624},
issn = {1468-1331},
}

@article {pmid40258293,
year = {2025},
author = {Elsayyid, M and Tanis, JE and Yu, Y},
title = {Simple In-Cell Processing Enables Deep Proteome Analysis of Low-Input Caenorhabditis elegans.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.4c05003},
pmid = {40258293},
issn = {1520-6882},
abstract = {Caenorhabditis elegans is a widely used genetic model organism; however, the worm cuticle complicates extraction of intracellular proteins, a prerequisite for typical bottom-up proteomics. Conventional physical disruption procedures are not only time-consuming but can also cause significant sample loss, making it difficult to perform proteomics with low-input samples. Here, for the first time, we present an on-filter in-cell (OFIC) processing approach that can digest C. elegans proteins directly in the cells of the organism after methanol fixation. With OFIC processing and single-shot LC-MS analysis, we identified over 9400 proteins from a sample of only 200 worms, the largest C. elegans proteome reported to date that did not require fractionation or enrichment. We systematically evaluated the performance of the OFIC approach by comparing it to conventional lysis-based methods. Our data suggest superior performance of OFIC processing for C. elegans proteome identification and quantitation. We further evaluated the OFIC approach with even lower-input samples, including single worms. Then, we used this method to determine how the proteome is impacted by loss of superoxide dismutase sod-1, the ortholog of human SOD1, a gene associated with amyotrophic lateral sclerosis. Analysis of 8800 proteins from only 50 worms as the initial input showed that loss of sod-1 affects the abundance of proteins required for stress response, ribosome biogenesis, and metabolism. In conclusion, our streamlined OFIC approach, which can be broadly applied to other systems, minimizes sample loss while offering the simplest workflow reported to date for C. elegans proteomics.},
}

@article {pmid40256588,
year = {2024},
author = {Ahmady, H and Afrand, M and Motaqi, M and Meftahi, GH},
title = {Utilizing Sertoli Cell Transplantation as a Therapeutic Technique for the Management of Neurodegenerative Diseases.},
journal = {Archives of Razi Institute},
volume = {79},
number = {4},
pages = {701-710},
pmid = {40256588},
issn = {2008-9872},
mesh = {*Neurodegenerative Diseases/therapy ; Humans ; Male ; Animals ; *Sertoli Cells/transplantation ; },
abstract = {Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), are defined by aberrant protein accumulation, brain atrophy, and gradual decline of neuronal function. Despite the considerable endeavors devoted to discovering treatments for NDs in recent decades, the demand for efficient therapeutic agents persists. Sertoli cells (SCs) play a crucial role in providing a supportive structure and environment for the development of germ cells. SCs, whether transplanted as xenogeneic or allogeneic cells, present a viable choice for enhancing graft persistence via the release of immunomodulatory and trophic factors, including neurturin (NTN), platelet-derived growth factor, Fas (CD95) ligand (FasL), glial-derived neurotrophic factor, interleukin 1 (IL1), brain-derived neurotrophic factor, interleukin 6 (IL6), transforming growth factors, and vascular growth factor, that protect replaced cells and tissues from the immune system. However, there is currently no cohesive evidence regarding the neuroprotective influence of the transplantation of SCs on NDs. Therefore, this review focuses on assessing stem cells' neuroprotective impact on neurodegenerative diseases in pre-clinical settings and presenting cohesive information. A comprehensive search was conducted between 2000 and 2022. In the identification stage, after a comprehensive search across databases, including Web of Science, Scopus, and PubMed/Medline, 103 papers were obtained. The search conducted in the present study yielded a total of nine relevant papers on the therapeutic effect of the transplantation of SCs on NDs. It was found that the transplantation of SCs exhibits a promising impact on enhancing the symptoms of neurological diseases in rats. The findings highlight the need for multiple standardized pre-clinical trials to find reliable information to confirm the utilization of the transplantation of SCs and the reduction of the symptoms of neurodegenerative diseases.},
}

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

@article {pmid40255098,
year = {2025},
author = {Regnault, R and Kouach, M and Goossens, L and Thuru, X and Bailly, C and Goossens, JF},
title = {HR-MS Analysis of the Covalent Binding of Edaravone to 5-Formylpyrimidine Bases and a DNA Oligonucleotide Containing a 5-Formylcytidine Residue.},
journal = {Rapid communications in mass spectrometry : RCM},
volume = {39},
number = {14},
pages = {e10050},
doi = {10.1002/rcm.10050},
pmid = {40255098},
issn = {1097-0231},
support = {//Comité de l'Oise de la Ligue Contre le Cancer/ ; //French Ligue Against Cancer/ ; },
mesh = {Edaravone/chemistry ; *Mass Spectrometry/methods ; *Oligonucleotides/chemistry/metabolism ; *Pyrimidines/chemistry ; *DNA/chemistry ; *Cytidine/chemistry/analogs & derivatives ; Cytosine/analogs & derivatives ; },
abstract = {RATIONALE: Edaravone (EDA) is a radical scavenger and an antioxidant drug approved to treat amyotrophic lateral sclerosis and used as a research tool to explore treatment of neurodegenerative diseases and cancers. It is also a reactive agent, known as PMP (1-phenyl-3-methyl-5-pyrazolone), used for the analysis of polysaccharides composition. EDA can react with sugars and aromatic aldehydes. In this context, we have investigated the reactivity of EDA toward the biologically relevant formylated nucleobases, nucleosides, and an oligonucleotide containing a formylated residue.

METHODS: The formation of both mono- and bis-adducts between EDA and the formylated nucleobases (5-formyluracil (5fU) and 5-formylcytosine (5fC)) or the corresponding nucleosides 5-fdU and 5-fdC was characterized using high-resolution mass spectrometry (HR-MS). Similarly, the covalent binding of EDA to an 8-mer palindromic oligonucleotide d (TATG[*C]ATA) containing a single 5-fdC residue [*C] under physiological conditions was investigated using mass spectrometry.

RESULTS: For the first time, EDA is shown to react with formylated pyrimidines. Covalent and stable adducts were identified. EDA was found to react efficiently with the formylated oligonucleotide to generate mono- and bis-adducts. The rate of formation of the mono-adduct was five times higher than that of the bis-adduct. The reaction of EDA with aldehydic DNA modifications such as 5fU/5fC may have important consequences in terms of gene expression.

CONCLUSIONS: These observations raise implications for an epigenetic contribution to the mechanism of action of EDA. The biological implications of our in vitro results are discussed, notably in the frame of neurodegenerative diseases and cancers.},
}

Edaravone/chemistry
*Mass Spectrometry/methods
*Oligonucleotides/chemistry/metabolism
*Pyrimidines/chemistry
*DNA/chemistry
*Cytidine/chemistry/analogs & derivatives
Cytosine/analogs & derivatives

@article {pmid40254405,
year = {2025},
author = {Shevchuk, DV and Tukhvatulin, AI and Dzharullaeva, AS and Berdalina, IA and Zakharova, MN},
title = {Molecular Biomarkers of Neurodegeneration in Amyotrophic Lateral Sclerosis.},
journal = {Biochemistry. Biokhimiia},
volume = {90},
number = {2},
pages = {276-288},
doi = {10.1134/S0006297924604039},
pmid = {40254405},
issn = {1608-3040},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/diagnosis/pathology/blood ; Biomarkers/metabolism/blood ; Male ; Female ; Middle Aged ; Aged ; Amyloid beta-Peptides/metabolism/blood ; Adult ; tau Proteins/metabolism/blood ; Clusterin ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disease. However, definitive diagnosis could be delayed by up to 12 months due to the lack of specific and sensitive biomarkers for ALS. In our study, conducted for the first time on a large cohort of ALS patients (n = 100) within the Russian population, we assessed key biomarkers of neurodegenerative pathology, including β-amyloids (Aβ40 and Aβ42) and tau proteins (Tau-total and Tau-p181), as well as other pathogenetically relevant, promising biomarkers such as FGF-21, Kallikrein-6 (KLK-6), NCAM-1, Neurogranin (NRGN), TDP-43, Apolipoprotein E4, Clusterin (Apo J), Complement Factor H, Fetuin-A, α2-Macroglobulin, Apo AI, Apo CIII, Apo E, Complement C3, GDNF, sRAGE, and S100B protein. Significant differences between the ALS patients and the control group were observed for Aβ40 (p = 0.044), Aβ42 (p < 0.001), FGF-21 (p < 0.001), Tau-total (p = 0.001), Tau-p181 (p = 0.014), Clusterin (p < 0.001), Complement C3 (p = 0.001), and S100B (p = 0.024). A significant direct correlation was found between the ALSFRS-R score and concentrations of Aβ40 and Aβ42. Changes in the complement system (Complement C3 and Complement Factor H) were identified, highlighting critical role of neuroinflammatory processes in ALS pathogenesis. Additionally, increased levels of FGF-21 were observed in the patients with the bulbar onset of ALS. Significant increase in the concentration of the chaperone protein clusterin in the patients with rapid disease progression suggests its potential as a prognostic biomarker for motor neuron disease. Furthermore, its role in maintaining proteostasis could provide novel therapeutic targets.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/diagnosis/pathology/blood
Biomarkers/metabolism/blood
Male
Female
Middle Aged
Aged
Amyloid beta-Peptides/metabolism/blood
Adult
tau Proteins/metabolism/blood
Clusterin

@article {pmid40254295,
year = {2025},
author = {Epel, ES and White, KE and Brownell, KD and Rodin, J and Hollis, AL and Diefenbach, MA and Alegria, KE and Fromer, E and Czajkowski, SM and Bacon, SL and Revenson, TA and Ruiz, J and Maibach, E and , },
title = {Transforming Health Psychology and Behavioral Medicine to Address the Climate Crisis: A Call for Strategic Research and Advocacy.},
journal = {Annals of behavioral medicine : a publication of the Society of Behavioral Medicine},
volume = {59},
number = {1},
pages = {},
doi = {10.1093/abm/kaae088},
pmid = {40254295},
issn = {1532-4796},
mesh = {Humans ; *Climate Change ; *Behavioral Medicine ; *Health Behavior ; Social Change ; },
abstract = {OBJECTIVE: The climate crisis poses the largest threat to human health and survival and has been a public health emergency for many years. It is causing harmful consequences for physical and mental health and is amplifying existing health inequities. In this call to action, we highlight the relevance of the health psychology and behavioral medicine communities in addressing the health impacts of climate change.

METHOD: We identify mitigation and adaptation climate health behaviors and social changes needed that underlie the three essential objectives to address climate change and its associated health consequences: (a) rapid decarbonization, (b) drawdown of atmospheric heat-trapping gases (sequestration), and (c) adap- tation.

RESULTS: To advance the behavioral and systemic changes necessary to protect health, we propose a 1-2-3 Transformational Model in which the larger field of health psychology and behavioral medicine promotes (1) One Health, human and planetary health by (2) targeting climate health behaviors, and (3) social change across major professional areas, including research, interventions, and education/advo- cacy. We urge the adoption of the social quantum change paradigm, a systems approach to understanding the process of social change, where systemic change is viewed as local to global, and the individual has an influential role.

DISCUSSION: These shifts in views, priorities, and methods will bolster hope, collective efficacy, and action to support the next generation of health psychology and behavioral medicine profession- als. With these changes, the health psychology and behavioral medicine communities can have a more immediate and meaningful impact on the climate crisis and its associated health consequences.},
}

Humans
*Climate Change
*Behavioral Medicine
*Health Behavior
Social Change

@article {pmid40254133,
year = {2025},
author = {Turner-Ivey, B and Jenkins, DP and Carroll, SL},
title = {Multiple Roles for Neuregulins and their ERBB Receptors in Neurodegenerative Disease Pathogenesis and Therapy.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2025.03.012},
pmid = {40254133},
issn = {1525-2191},
abstract = {The role that neurotrophins such as nerve growth factor play in the pathogenesis of neurodegenerative diseases has long been appreciated. However, the neuregulin (NRG) family of growth factors and/or their ERBB receptors have also been implicated in the pathogenesis of conditions such as Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). In this review, we consider (1) the structural variability of NRG isoforms generated by alternative RNA splicing, the use of multiple promoters and proteolysis and the impact that this structural variability has on neuronal and glial physiology during development and adulthood. We discuss (2) the NRG receptors ERBB2, ERBB3 and ERBB4, how activation of each of these receptors further diversifies NRG actions in the central nervous system and how dementia-related proteins such as γ-secretase modulate the action of NRGs and their ERBB receptors. We then (3) turn to the abnormalities in NRG and ERBB expression and function evident in human AD and mouse AD models, how these abnormalities affect brain function, and attempts to use NRGs to treat AD. Finally, (4) we discuss NRG effects on the survival and function of neurons relevant to FTLD and ALS, alterations in NRG/ERBB signaling identified in these conditions and the recent discovery of multiple human pedigrees in which autosomal dominant FTLD/ALS potentially results from point mutations in ERBB4.},
}

@article {pmid40253599,
year = {2025},
author = {Malik, M and Bhatti, T and Hodson-Tole, E and Onambele-Pearson, G and Chaouch, A},
title = {Physical activity in amyotrophic lateral sclerosis: a systematic review of the methodologies used to assess a possible association.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-18},
doi = {10.1080/21678421.2025.2488298},
pmid = {40253599},
issn = {2167-9223},
abstract = {Growing evidence suggests that strenuous physical activity (PA) may be associated with an increased risk of developing Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease. However, there are inconsistent findings across studies that may reduce our understanding of any potential associations. We propose that these differences may reflect the tools used to record historical PA. We conducted a systematic review evaluating the risk of developing ALS due to PA. The inclusion criteria were met by 22/113 studies, and an association between increasing PA and ALS was found in 15 studies. Studies that found a positive association were more likely to have longer recall periods and convert data into Metabolic Equivalent of Task values. Studies that did not find an association with increasing PA were more likely to use questionnaires with no validity or reliability data. Questionnaires with validity data all showed at least a moderate correlation of PA compared to objective measures, with reliability ranging from poor to good. Study designs included prospective cohort and case-control, which may also contribute to heterogeneity in findings. This work highlights the need for consensus on the type of questionnaire to use to assess potential associations between PA and ALS.},
}

@article {pmid40252901,
year = {2025},
author = {Baidya, AT and Dante, D and Das, B and Wang, L and Darreh-Shori, T and Kumar, R},
title = {Discovery and characterization of novel pyridone and furan substituted ligands of choline acetyltransferase.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {177638},
doi = {10.1016/j.ejphar.2025.177638},
pmid = {40252901},
issn = {1879-0712},
abstract = {The key to the management of two devastating diseases, namely Alzheimer's Disease (AD) and Amyotrophic Lateral Sclerosis (ALS) lies in an early diagnosis, which is difficult due to its multifactorial nature. However, a common hallmark of AD and ALS is degeneration of cholinergic system. Choline acetyltransferase (ChAT) has been proposed as a potential target for development of cholinergic-specific biomarker. However, lack of selective, potent, brain permeable molecular probes of ChAT hinder development of ChAT biomarkers. In this study, we have successfully utilised structure-based virtual screening approach and identified two ChAT inhibitors from a database of 1.4 million compounds. The compounds were then subjected to rigorous in vitro characterization. Compound V6 showed Ki value of 11 μM and IC50 value of 21.73 μM, while V15 showed Ki and IC50 values of 4.5 and 9.42 μM, respectively for ChAT enzyme. V6 and V15 showed good solubility of 0.21 mg/ml and 0.17 mg/ml respectively and cytotoxicity analysis indicated no toxicity. We also performed a 200 ns molecular dynamics simulation, which revealed the intricate interaction dynamics for V6 and V15 with ChAT binding pocket. Moreover, the Tanimoto similarity analysis indicated the novelty and structural diversity of the hits. In conclusion, these validated hits provide a platform to develop potent, selective, blood-brain barrier permeable small molecules as chemical probes of ChAT or as Positron Emission Tomography tracer for early diagnosis and/or in vivo monitoring of the effect of new therapeutic candidates in spectrum of neurodegenerative disorders, in which cholinergic deficit is one of the hallmarks.},
}

@article {pmid40252666,
year = {2025},
author = {Balendra, R and Sreedharan, J and Hallegger, M and Luisier, R and Lashuel, HA and Gregory, JM and Patani, R},
title = {Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy.},
journal = {The Lancet. Neurology},
volume = {24},
number = {5},
pages = {456-470},
doi = {10.1016/S1474-4422(25)00109-7},
pmid = {40252666},
issn = {1474-4465},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *TDP-43 Proteinopathies/genetics/pathology ; *Mutation/genetics ; },
abstract = {Mutations in the TARDBP gene, which encodes the TDP-43 protein, account for only 3-5% of familial cases of amyotrophic lateral sclerosis and less than 1% of cases that are apparently idiopathic. However, the discovery of neuronal inclusions of TDP-43 as the neuropathological hallmark in the majority of cases of amyotrophic lateral sclerosis has transformed our understanding of the pathomechanisms underlying neurodegeneration. An individual TARDBP mutation can cause phenotypic heterogeneity. Most mutations lie within the C-terminus of the TDP-43 protein. In pathological conditions, TDP-43 is mislocalised from the nucleus to the cytoplasm, where it can be phosphorylated, cleaved, and form insoluble aggregates. This mislocalisation leads to dysfunction of downstream pathways of RNA metabolism, proteostasis, mitochondrial function, oxidative stress, axonal transport, and local translation. Biomarkers for TDP-43 dysfunction and targeted therapies are being developed, justifying cautious optimism for personalised medicine approaches that could rescue the downstream effects of TDP-43 pathology.},
}

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

@article {pmid40252655,
year = {2025},
author = {Dame, PS},
title = {The four most common genetic subtypes of amyotrophic lateral sclerosis: state of the art and future directions.},
journal = {The Lancet. Neurology},
volume = {24},
number = {5},
pages = {380-381},
doi = {10.1016/S1474-4422(25)00117-6},
pmid = {40252655},
issn = {1474-4465},
}

@article {pmid40251832,
year = {2025},
author = {Bresque, M and Esteve, D and Balmer, G and Hamilton, HL and Stephany, JS and Pehar, M and Vargas, MR},
title = {FABP7 Expression Modulates the Response of Astrocytes to Induced Endotoxemia.},
journal = {Glia},
volume = {},
number = {},
pages = {},
doi = {10.1002/glia.70023},
pmid = {40251832},
issn = {1098-1136},
support = {R01NS122973/NH/NIH HHS/United States ; R01NS132760/NH/NIH HHS/United States ; },
abstract = {Fatty acid binding proteins (FABPs) are a family of small proteins involved in fatty acid (FA) subcellular trafficking. In the adult central nervous system, FABP7, one of the members of this family, is highly expressed in astrocytes and participates in lipid metabolism, regulation of gene expression, and energy homeostasis. Reactive astrocytes in Alzheimer's disease and amyotrophic lateral sclerosis animal models upregulate FABP7 expression. This upregulation may contribute to the pro-inflammatory phenotype that astrocytes display during neurodegeneration and is detrimental for co-cultured neurons. Here, we explore how FABP7 expression modulates astrocyte response to inflammatory stimuli. Our results showed that silencing FABP7 expression in astrocyte cultures before treatment with different inflammatory stimuli decreases the expression of a luciferase reporter expressed under the control of NF-κB -response elements. Correspondingly, FABP7-silenced astrocytes display decreased nuclear translocation of the NF-κB-p65 subunit in response to these stimuli. Moreover, silencing FABP7 decreases the toxicity of stimulated astrocytes toward co-cultured motor neurons. Similar results were obtained after silencing FABP7 in human astrocytes differentiated from induced pluripotent stem cells. Finally, knockdown of astrocytic FABP7 expression in vivo reduces glial activation in the cerebral cortex of mice after systemic bacterial lipopolysaccharide (LPS) administration. In addition, whole transcriptome RNA sequencing analysis from the cerebral cortex of LPS-treated mice showed a differential inflammatory transcriptional profile, with attenuation of NF-κB-dependent transcriptional response after FABP7 knockdown. Together, our results highlight the potential of FABP7 as a target to modulate neuroinflammation in the central nervous system.},
}

@article {pmid40251218,
year = {2025},
author = {Abid, MN and Siming, L and Chao, H and Amin, M and Sarwer, S},
title = {Enhancing faculty teaching performance through constructive leadership with a mediating role of job satisfaction.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {13454},
pmid = {40251218},
issn = {2045-2322},
mesh = {*Job Satisfaction ; *Leadership ; Humans ; Male ; Female ; Cross-Sectional Studies ; *Teaching ; Adult ; *Faculty/psychology ; Universities ; Pakistan ; Middle Aged ; Surveys and Questionnaires ; },
abstract = {This study explored the impact of constructive leadership styles including transformational leadership (TLS), authentic leadership (ALS), and servant leadership (SLS) on faculty teaching performance (FTP), with job satisfaction (JS) acting as a critical mediator. Using a cross-sectional design and convenience sampling, data were collected from 346 faculty members across six universities in Lahore, Pakistan. Structural equation modeling (SEM) and regression analysis revealed that all three leadership styles significantly enhanced FTP, with transformational leadership showing the strongest influence. Authentic and servant leadership also demonstrated robust positive effects. Job satisfaction emerged as a pivotal mediator, strengthening the relationship between CLS and FTP.These findings highlight the transformative potential of constructive leadership in improving teaching performance and emphasize the critical role of department heads in fostering such practices. By prioritizing strategies to enhance employee motivation and satisfaction, institutions can improve retention, productivity, and overall academic excellence. This study reinforces existing literature on leadership and teaching performance while providing novel insights into the mediating role of job satisfaction, offering actionable implications for academic leadership and organizational development.},
}

*Job Satisfaction
*Leadership
Humans
Male
Female
Cross-Sectional Studies
*Teaching
Adult
*Faculty/psychology
Universities
Pakistan
Middle Aged
Surveys and Questionnaires

@article {pmid40250284,
year = {2025},
author = {Calma, AD and Pavey, N and Silva, CS and van den Bos, MAJ and Yiannikas, C and Farrar, MA and Kiernan, MC and Menon, P and Vucic, S},
title = {Diagnostic utility of threshold tracking TMS paradigms in early amyotrophic lateral sclerosis.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {174},
number = {},
pages = {105-113},
doi = {10.1016/j.clinph.2025.03.044},
pmid = {40250284},
issn = {1872-8952},
abstract = {OBJECTIVE: Threshold tracking transcranial magnetic stimulation (TMS) has exhibited utility as a diagnostic technique in Amyotrophic Lateral Sclerosis (ALS). Different threshold tracking paradigms have recently been proposed. The present study assessed the diagnostic utility of serial ascending and parallel threshold tracking TMS in ALS.

METHODS: Threshold tracking TMS was undertaken on 90 prospectively recruited participants suspected of ALS. Short interval intracortical inhibition (SICI) was recorded with serial ascending and parallel threshold tracking paradigms between Interstimulus Interval (ISI) 1-to-7 ms. The primary outcome measure was differences in diagnostic utility of the paradigms in differentiating ALS from ALS mimicking disorders using receiver operating characteristic (ROC) analysis (DeLong statistical method).

RESULTS: Reduction in SICI reliably differentiated ALS from mimic disorders, irrespective of the threshold tracking paradigm. Comparison of area under the curve (AUC) established a significantly higher value for mean SICI (1-7 ms) with the serial ascending SICI paradigm (0.81, 95 % confidence interval 0.72-0.91) compared to the parallel paradigm (SICI 0.72, 95 % confidence interval 0.61-0.83, p = 0.0065). The better diagnostic utility of serial ascending paradigm was evident for SICI recorded between 1-to-5 ms, and was maintained irrespective of disease onset site, degree of functional impairment, and the degree of lower motor neuron dysfunction. A comparable diagnostic utility across threshold tracking paradigms was evident in ALS participants who presented with a relative paucity of upper motor neuron signs.

CONCLUSION: While threshold tracking TMS reliably differentiated ALS from mimic disorders, the present study established better diagnostic utility with the serial ascending threshold tracking TMS paradigm.

SIGNIFICANCE: The serial ascending threshold tracking TMS should be used in a clinical setting as a diagnostic tool for ALS.},
}

@article {pmid40250093,
year = {2025},
author = {Casiraghi, V and Pellegrini, E and Brusati, A and Peverelli, S and Invernizzi, S and Santangelo, S and Colombrita, C and Verde, F and Ticozzi, N and Silani, V and Ratti, A},
title = {Characterization of human healthy i[3] lower motor neurons exposed to CSF from ALS patients stratified by UNC13A and C9ORF72 genotype.},
journal = {Journal of the neurological sciences},
volume = {473},
number = {},
pages = {123508},
doi = {10.1016/j.jns.2025.123508},
pmid = {40250093},
issn = {1878-5883},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting upper and lower motor neurons. Neurodegeneration in ALS might be driven by proteotoxicity or neuroinflammation, which have also been proposed to be promoted by toxic components of the cerebrospinal fluid (CSF). We investigated the possible toxicity of ALS CSF on healthy induced pluripotent stem cells (iPSC)-derived integrated, inducible, and isogenic lower motor neurons (i[3]LMNs). CSFs were obtained from ALS patients homozygous for the risk UNC13A rs12608932 single nucleotide polymorphism (CC) and for the corresponding major allele (AA), ALS patients with C9ORF72 hexanucleotide repeat expansion, and individuals affected by normal pressure hydrocephalus as non-disease controls (ND). A chronic and low-dose sodium arsenite (ARS) treatment was used as positive control of oxidative stress. We found that 10 % ALS CSF treatment for 48 h was not sufficient to induce significant alterations in viability, autophagic flux, axonal degeneration, DNA damage, and Golgi apparatus integrity in healthy i[3]LMNs, in contrast to ARS treatment. Only UNC13A CC CSF significantly increased protein aggregation and Golgi apparatus fragments dimension. RNA-sequencing revealed that all ALS and ND CSFs induced expression changes of few genes, while chronic ARS deregulated the expression of thousands of genes, mostly involved in inflammation and synapse biology. In this work, we demonstrated that in our experimental settings only CSF from UNC13A CC patients induced some ALS-associated pathological features in healthy i[3]LMNs. Further studies will be required to elucidate the mechanistic link between the risk UNC13A genotype and CSF composition and toxicity.},
}

@article {pmid40249897,
year = {2025},
author = {Siegler, JE and Galetta, SL},
title = {Editors' Note: Physical Activity, Fitness, and Long-Term Risk of Amyotrophic Lateral Sclerosis: A Prospective Cohort Study.},
journal = {Neurology},
volume = {104},
number = {9},
pages = {e213609},
doi = {10.1212/WNL.0000000000213609},
pmid = {40249897},
issn = {1526-632X},
}

@article {pmid40249896,
year = {2025},
author = {Kawada, T},
title = {Reader Response: Physical Activity, Fitness, and Long-Term Risk of Amyotrophic Lateral Sclerosis: A Prospective Cohort Study.},
journal = {Neurology},
volume = {104},
number = {9},
pages = {e209943},
doi = {10.1212/WNL.0000000000209943},
pmid = {40249896},
issn = {1526-632X},
}

@article {pmid40249895,
year = {2025},
author = {Vaage, AM and Nakken, O},
title = {Author Response: Physical Activity, Fitness, and Long-Term Risk of Amyotrophic Lateral Sclerosis: A Prospective Cohort Study.},
journal = {Neurology},
volume = {104},
number = {9},
pages = {e209962},
doi = {10.1212/WNL.0000000000209962},
pmid = {40249895},
issn = {1526-632X},
}

@article {pmid40248372,
year = {2025},
author = {Dai, ZS and Zhang, M and Deng, YY and Zhou, N and Tian, Y},
title = {Efficacy of a novel artificial liver versatile plasma purification system in patients with acute-on-chronic liver failure.},
journal = {World journal of gastroenterology},
volume = {31},
number = {14},
pages = {103892},
pmid = {40248372},
issn = {2219-2840},
mesh = {Humans ; *Acute-On-Chronic Liver Failure/mortality/therapy/blood ; Female ; Male ; Middle Aged ; Prospective Studies ; *Liver, Artificial ; Treatment Outcome ; Aged ; Patient Readmission/statistics & numerical data ; Adult ; Length of Stay/statistics & numerical data ; Kaplan-Meier Estimate ; Follow-Up Studies ; Peritonitis/epidemiology/etiology ; China/epidemiology ; },
abstract = {BACKGROUND: We have innovatively amalgamated membrane blood purification and centrifugal blood cell separation technologies to address the limitations of current artificial liver support (ALS) models, and develop a versatile plasma purification system (VPPS) through centrifugal plasma separation.

AIM: To investigate the influence of VPPS on long-term rehospitalization and mortality rates among patients with acute-on-chronic liver failure (ACLF).

METHODS: This real-world, prospective study recruited inpatients diagnosed with ACLF from the Second Xiangya Hospital of Central South University between October 2021 and March 2024. Patients were categorized into the VPPS and non-VPPS groups based on the distinct ALS models administered to them. Self-administered questionnaires, clinical records, and self-reported data served as the primary methods for data collection. The laboratory results were evaluated at six distinct time points. All patients were subjected to follow-up assessments for > 12 months. Kaplan-Meier survival analyses and Cox proportional hazards models were used to evaluate the risks of hospitalization and mortality during the follow-up period.

RESULTS: A cohort of 502 patients diagnosed with ACLF was recruited, with 260 assigned to the VPPS group. On comparing baseline characteristics, the VPPS group exhibited a significantly shorter length of stay, higher incidence of spontaneous peritonitis and pulmonary aspergillosis compared to the non-VPPS group (P < 0.05). Age [hazard ratio (HR) = 1.142, 95%CI: 1.01-1.23, P = 0.018), peritonitis (HR = 2.825, 95%CI: 1.07-6.382, P = 0.026), albumin (HR = 0.67, 95%CI: 0.46-0.942, P = 0.023), total bilirubin (HR = 1.26, 95%CI: 1.01-3.25, P = 0.021), international normalized ratio (HR = 1.97, 95%CI: 1.21-2.908, P = 0.014), and VPPS/non-VPPS (HR = 3.24, 95%CI: 2.152-4.76, P < 0.001) were identified as significant independent predictors of mortality in both univariate and multivariate analyses throughout the follow-up period. Kaplan-Meier survival analyses demonstrated significantly higher rehospitalization and mortality rates in the non-VPPS group compared to the VPPS group during follow-up of ≥ 2 years (log-rank test, P < 0.001).

CONCLUSION: These findings suggest that VPPS is safe and has a positive influence on prognostic outcomes in patients with ACLF.},
}

Humans
*Acute-On-Chronic Liver Failure/mortality/therapy/blood
Female
Male
Middle Aged
Prospective Studies
*Liver, Artificial
Treatment Outcome
Aged
Patient Readmission/statistics & numerical data
Adult
Length of Stay/statistics & numerical data
Kaplan-Meier Estimate
Follow-Up Studies
Peritonitis/epidemiology/etiology
China/epidemiology

@article {pmid40247237,
year = {2025},
author = {Pehlivanidis, A and Kouklari, EC and Kalantzi, E and Korobili, K and Tagkouli, E and Papanikolaou, K},
title = {Self-reported symptoms of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and affective lability in discriminating adult ADHD, ASD and their co-occurrence.},
journal = {BMC psychiatry},
volume = {25},
number = {1},
pages = {391},
pmid = {40247237},
issn = {1471-244X},
abstract = {BACKGROUND: To diagnose and manage adults with Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), or their co-occurrence (ADHD + ASD), clinicians must identify specific features that differentiate these diagnostic categories. Self-report questionnaires targeting specific features are widely used and, together with clinical assessments, provide reliable diagnoses. Although affective lability is present in various psychiatric disorders, it lacks specificity when screening for ADHD in the general population, and its discriminant value for ADHD, ASD, and ADHD + ASD has not been studied.

METHODS: This study involved 300 adults without intellectual developmental disorder (188 male) who received an ADHD (n = 174), ASD (n = 68), or ADHD + ASD (n = 58) diagnosis after a multidisciplinary consensus decision according to DSM-5 criteria. Before clinical assessment, all patients requesting evaluation for one of these diagnoses completed questionnaires on an online platform. The assessment instruments included a modified version of the Barkley Adult ADHD Rating Scale (BAARS IV) for ADHD, the Autism Spectrum Quotient (AQ) and the Empathy Quotient (EQ) for ASD features, and the Affective Lability Scale (ALS) for affective lability. Total scores and sub-scores of the instruments were compared among the three groups. Additionally, stepwise logistic regression analyses were conducted to identify specific measures that contribute to group discrimination.

RESULTS: Results revealed distinct patterns in symptomatology as expected. The ADHD and the ADHD + ASD groups presented significantly higher ALS total score compared to ASD. Stepwise logistic regression analyses identified specific measures contributing to group differentiation. ASD vs. ADHD + ASD discrimination included BAARS IV current total score and EQ total score. The subscale anger from ALS in addition with BAARS IV past total score and AQ total score were the factors that discriminated ADHD diagnosis from the co-occurrence of ADHD and ASD. Finally, BAARS IV past total score, BAARS IV current inattention, AQ total score, and EQ total score were found to differentiate ADHD from ASD.

CONCLUSIONS: The study highlights the significance of incorporating emotional dimensions in diagnostic frameworks and may contribute valuable insights for clinicians differentiating neurodevelopmental conditions.},
}

@article {pmid40247229,
year = {2025},
author = {Samudi Raju, C and Kono, M and Looi, KW and Ong, JX and Tan, CA and Ang, CS and Tan, PHY and Shamnugam, H and Sekaran, SDKC and Syed Omar, SF and Lum, LCS},
title = {Low atypical lymphocyte score as a predictor of non-severe dengue.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {551},
pmid = {40247229},
issn = {1471-2334},
abstract = {BACKGROUND: Severe dengue has been linked to the presence of atypical lymphocytes, which can be quantified using the Q-flag parameter on a hematology analyzer. A higher atypical lymphocyte count has previously been associated with severe dengue. We aimed to evaluate the feasibility of the atypical lymphocyte score to provide an early prognosis for dengue severity.

METHOD: A prospective observational study enrolled adult patients admitted to the Infectious Disease ward with a febrile illness of less than 7 days. Blood samples obtained daily until discharge, were processed with XN-20 hematology analyzer with specific attention given to atypical lymphocyte score. Severe dengue cases were classified according to the 2009 World Health Organization Classification.

RESULTS: A total of 287 cases of laboratory-confirmed dengue, including 25 severe cases, were included. Dengue fever compared to non-dengue patients manifested increased lymphocytes within the high fluorescent zone on Day 6, The atypical lymphocyte score (ALS) of severe dengue showed an early rise, reaching a saturation point of 300 and remaining stable within the timeframe of days 4 to 8 post-fever onset. All but one severe dengue patient had a score exceeding 100 on day 4 post fever onset.

CONCLUSION: An atypical lymphocyte score below 100 on day 4 post fever onset, may serve as a predictive indicator that severe dengue is less likely to develop, potentially allowing for a lower level of medical intervention. These findings may contribute to more efficient resource allocation during outbreaks.

TRIAL REGISTRATION: The study was registered under National Medical Research Registration of Malaysia, (NMRR-18-3347-45473, 1 Sept 2019).},
}

@article {pmid40245393,
year = {2025},
author = {Musson, LS and Mitic, N and Leigh-Valero, V and Onambele-Pearson, G and Knox, L and Steyn, FJ and Holdom, CJ and Dick, TJ and van Eijk, RP and van Unnik, JW and Botman, LC and Beswick, E and Murray, D and Griffiths, A and McDermott, C and Hobson, E and Chaouch, A and Hodson-Tole, E},
title = {The Use of Digital Devices to Monitor Physical Behavior in Motor Neuron Disease: Systematic Review.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e68479},
doi = {10.2196/68479},
pmid = {40245393},
issn = {1438-8871},
mesh = {Humans ; *Motor Neuron Disease/physiopathology ; *Exercise ; *Wearable Electronic Devices ; },
abstract = {BACKGROUND: Motor neuron disease (MND) is a progressive and incurable neurodegenerative disease. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is the primary clinical tool for assessing disease severity and progression in MND. However, despite its widespread use, it does not adequately capture the extent of physical function decline. There is an urgent need for sensitive measures of disease progression that can be used to robustly evaluate new treatments. Measures of physical function derived from digital devices are beginning to be used to assess disease progression. There is value in establishing a consensus approach to standardizing the use of such devices.

OBJECTIVE: We aimed to explore how digital devices are being used to quantify free-living physical behavior in MND. We evaluated the feasibility and assessed the implications for monitoring physical behavior for future clinical trials and clinical practice.

METHODS: Systematic searches of 4 databases were performed in October 2023 and June 2024. Peer-reviewed English-language articles (including preprints) that examined how people living with MND used digital devices to assess their free-living physical behavior were included. Study reporting quality was assessed using a 22-item checklist (maximum possible score=44 points).

RESULTS: In total, 12 articles met the inclusion criteria for data extraction. All studies were longitudinal and observational in design, but data collection, analysis, and reporting protocols varied. Quality assessment scores ranged between 19 and 40 points. Sample sizes ranged between 10 and 376 people living with MND at baseline, declining over the course of the study. Most studies used an accelerometer device worn on the wrist, chest, hip, or ankle. Participants were typically asked to continuously wear devices for 1 to 8 days at 1- to 4-month intervals, with studies running for 12 weeks to 24 months. Some studies asked participants to wear the device continuously for the full duration. Studies derived traditional end points focusing on duration, intensity, and frequency of physical activity or nontraditional end points focusing on features of an individual's movement patterns. The correlation coefficients (r) between physical behavior end points and ALSFRS-R ranged from 0.31 to 0.78. Greater monitoring frequencies and improved end point sensitivity were shown to provide smaller sample size requirements and shorter durations for hypothetical clinical trials. People living with MND found using devices acceptable and reported a low burden. Adherence assessed in 8 (67%) studies was good, ranging from approximately 86% to 96%, with differences evident between wear locations. The perspectives of other end users and implications on clinical practice were not explored.

CONCLUSIONS: Remote monitoring of free-living physical behavior in MND is in its infancy but has the potential to quantify physical function. It is essential to develop a consensus statement, working toward agreed and standardized methods for data collection, analysis, and reporting.},
}

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

@article {pmid40244212,
year = {2025},
author = {Zhang, M and Zhou, H and Pan, Y and Wei, L},
title = {A pregnant woman with a 5-year history of amyotrophic lateral sclerosis: A case report.},
journal = {International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijgo.70173},
pmid = {40244212},
issn = {1879-3479},
support = {202414030736//Medical and Health Science and Technology Project of Shandong Province/ ; ZHKY202423//Chinese Nursing Association Scientific Research Project/ ; QDFY+X 2023125//the Clinical Medicine +X Project of the Affiliated Hospital of Qingdao University/ ; },
}

@article {pmid40244186,
year = {2025},
author = {Hu, C and Jiang, Y and Ma, C and Xu, F and Cui, C and Du, X and Chen, J and Zhu, L and Yu, S and He, X and Yu, W and Wang, Y and Xu, X},
title = {Decreased Cdk2 Activity Hindered Embryonic Development and Parthenogenesis Induction in Silkworm, Bombyx mori L.},
journal = {International journal of molecular sciences},
volume = {26},
number = {7},
pages = {},
doi = {10.3390/ijms26073341},
pmid = {40244186},
issn = {1422-0067},
support = {2021C02072//Technological Grant of Zhejiang for Breeding New Agricultural Varieties/ ; 32100377//National Natural Science Foundation of China/ ; CARS-18//Key Scientific and the China Agriculture Research System of MOF and MARA/ ; },
mesh = {Animals ; *Bombyx/embryology/genetics/enzymology ; *Parthenogenesis/drug effects ; *Cyclin-Dependent Kinase 2/metabolism/antagonists & inhibitors/genetics ; *Embryonic Development/drug effects ; *Insect Proteins/metabolism/genetics/antagonists & inhibitors ; Female ; },
abstract = {Cyclin-dependent protein kinase 2 (Cdk2), an important member of the serine/threonine-specific protein kinase family, plays a critical regulatory role in biological processes. Previous studies have demonstrated that Cdk2 is involved in the arrest and resumption of meiosis in mammalian oocytes. In this study, we explored the function of Cdk2 through parthenogenetic lines (PLs) and corresponding amphigonic lines (ALs) in a model lepidopteran insect silkworm, Bombyx mori L. Our findings revealed a positive correlation between Cdk2 activity and the parthenogenesis induction rate. The pharmacological inhibition of Cdk2 using the specific inhibitor AUZ454 not only significantly reduced the parthenogenesis induction rate but also caused developmental delays in embryos. These results demonstrate that Cdk2 is essential for parthenogenesis success and is a potential target gene for biological reproductive regulation.},
}

Animals
*Bombyx/embryology/genetics/enzymology
*Parthenogenesis/drug effects
*Cyclin-Dependent Kinase 2/metabolism/antagonists & inhibitors/genetics
*Embryonic Development/drug effects
*Insect Proteins/metabolism/genetics/antagonists & inhibitors
Female

@article {pmid40244061,
year = {2025},
author = {Tseriotis, VS and Liampas, A and Lazaridou, IZ and Karachrysafi, S and Vavougios, GD and Hadjigeorgiou, GM and Papamitsou, T and Kouvelas, D and Arnaoutoglou, M and Pourzitaki, C and Mavridis, T},
title = {Repulsive Guidance Molecule-A as a Therapeutic Target Across Neurological Disorders: An Update.},
journal = {International journal of molecular sciences},
volume = {26},
number = {7},
pages = {},
doi = {10.3390/ijms26073221},
pmid = {40244061},
issn = {1422-0067},
mesh = {Humans ; Animals ; *Nervous System Diseases/metabolism/drug therapy ; *Nerve Tissue Proteins/metabolism/antagonists & inhibitors/genetics ; *GPI-Linked Proteins/metabolism/antagonists & inhibitors/genetics ; Molecular Targeted Therapy ; Neurodegenerative Diseases/metabolism/drug therapy ; },
abstract = {Repulsive guidance molecule-a (RGMa) has emerged as a significant therapeutic target in a variety of neurological disorders, including neurodegenerative diseases and acute conditions. This review comprehensively examines the multifaceted role of RGMa in central nervous system (CNS) pathologies such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, neuromyelitis optica spectrum disorder, spinal cord injury, stroke, vascular dementia, auditory neuropathy, and epilepsy. The mechanisms through which RGMa contributes to neuroinflammation, neuronal degeneration, and impaired axonal regeneration are herein discussed. Evidence from preclinical studies associate RGMa overexpression with negative outcomes, such as increased neuroinflammation and synaptic loss, while RGMa inhibition, particularly the use of agents like elezanumab, has shown promise in enhancing neuronal survival and functional recovery. RGMa's responses concerning immunomodulation and neurogenesis highlight its potential as a therapeutic avenue. We emphasize RGMa's critical role in CNS pathology and its potential to pave the way for innovative treatment strategies in neurological disorders. While preclinical findings are encouraging so far, further clinical trials are needed to validate the safety and efficacy of RGMa-targeted therapies.},
}

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

@article {pmid40243827,
year = {2025},
author = {Carvalho, MCR},
title = {Reviewed article: Almeida ALS, Sousa TMS, Caldeira TCM, Claro RM. Association between adherence to the Food Guide golden rule and health characteristics among adult Brazilian women: a cross-sectional study with VIGITEL data, 2018-2021. Epidemiol Serv Saude. 2025:34;20240232.},
journal = {Epidemiologia e servicos de saude : revista do Sistema Unico de Saude do Brasil},
volume = {34},
number = {},
pages = {e20240232.b},
doi = {10.1590/S2237-96222025v34e20240232.b},
pmid = {40243827},
issn = {2237-9622},
}

@article {pmid40243826,
year = {2025},
author = {Tramontt, C},
title = {Reviewed article: Almeida ALS, Sousa TMS, Caldeira TCM, Claro RM. Association between adherence to the Food Guide golden rule and health characteristics among adult Brazilian women: a cross-sectional study with VIGITEL data, 2018-2021. Epidemiol Serv Saude. 2025:34;20240232.},
journal = {Epidemiologia e servicos de saude : revista do Sistema Unico de Saude do Brasil},
volume = {34},
number = {},
pages = {e20240232.a},
doi = {10.1590/S2237-96222025v34e20240232.a},
pmid = {40243826},
issn = {2237-9622},
}

@article {pmid40243810,
year = {2025},
author = {Flores, SV and Lillo, P and Levi-Monsalve, A and Roco-Videla, Á and Montaña, R},
title = {Genetic ancestry and risk allele C9orf72 rs3849942 T for amyotrophic lateral sclerosis in Latin American populations.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {26},
number = {3-4},
pages = {379-381},
doi = {10.1080/21678421.2024.2447459},
pmid = {40243810},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/ethnology ; *C9orf72 Protein/genetics ; *Genetic Predisposition to Disease/genetics ; Latin America/epidemiology ; Alleles ; Female ; Male ; *Polymorphism, Single Nucleotide/genetics ; White People/genetics ; Middle Aged ; White ; },
abstract = {This study examines the relationship between genetic ancestry and the rs3849942 T allele, linked to ALS, in 347 Latin American individuals from the 1000 Genomes Project. Ancestry proportions were estimated using 446 AIMs, and associations were analyzed via logistic regression. Higher Native American ancestry significantly reduced the likelihood of carrying the T allele, while European ancestry increased it. These findings emphasize the importance of incorporating genetic diversity into ALS research.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/ethnology
*C9orf72 Protein/genetics
*Genetic Predisposition to Disease/genetics
Latin America/epidemiology
Alleles
Female
Male
*Polymorphism, Single Nucleotide/genetics
White People/genetics
Middle Aged
White

@article {pmid40243699,
year = {2025},
author = {Xu, R and Kang, Q and Yang, X and Yi, P and Zhang, R},
title = {Unraveling Molecular Targets for Neurodegenerative Diseases Through Caenorhabditis elegans Models.},
journal = {International journal of molecular sciences},
volume = {26},
number = {7},
pages = {},
doi = {10.3390/ijms26073030},
pmid = {40243699},
issn = {1422-0067},
support = {32270739//National Natural Science Foundation of China/ ; },
mesh = {*Caenorhabditis elegans/genetics/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/genetics/drug therapy/pathology ; *Disease Models, Animal ; Humans ; Caenorhabditis elegans Proteins/metabolism/genetics ; },
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and prion disease, represent a group of age-related disorders that pose a growing and formidable challenge to global health. Despite decades of extensive research that has uncovered key genetic factors and biochemical pathways, the precise molecular mechanisms underlying these diseases and effective therapeutic strategies remain elusive. Caenorhabditis elegans (C. elegans) has emerged as a powerful model organism for studying NDDs due to its unique biological features such as genetic tractability, conserved molecular pathways, and ease of high-throughput screening. This model provides an exceptional platform for identifying molecular targets associated with NDDs and developing novel therapeutic interventions. This review highlights the critical role of C. elegans in elucidating the complex molecular mechanisms of human NDDs, with a particular focus on recent advancements and its indispensable contributions to the discovery of molecular targets and therapeutic strategies for these NDDs.},
}

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

@article {pmid40243477,
year = {2025},
author = {Romano, R and Del Fiore, VS and Ruotolo, G and Mazzoni, M and Rosati, J and Conforti, FL and Bucci, C},
title = {Lysosomal Dysfunction in Amyotrophic Lateral Sclerosis: A Familial Case Linked to the p.G376D TARDBP Mutation.},
journal = {International journal of molecular sciences},
volume = {26},
number = {7},
pages = {},
doi = {10.3390/ijms26072867},
pmid = {40243477},
issn = {1422-0067},
support = {PRIN2022 N. 2022XTM2S3//Ministero dell'università e della ricerca/ ; PRIN2022 PNRR N. P2022FBZXY//Ministero dell'università e della ricerca/ ; D.M. n. 737 of 25.06.2021//Ministero dell'università e della ricerca/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Lysosomes/metabolism/pathology ; *DNA-Binding Proteins/genetics/metabolism ; Motor Neurons/metabolism/pathology ; *Mutation ; Fibroblasts/metabolism/pathology ; Male ; Female ; Induced Pluripotent Stem Cells/metabolism ; Middle Aged ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Consequent to the loss of these cells, neuromuscular functions decline, causing progressive weakness, muscle wasting, and paralysis, leading to death in 2 to 5 years. More than 90% of ALS cases are sporadic, while the remaining 10% of cases are familial, due to mutations in 40 different genes. One of the most common genes to be mutated in ALS is TARDBP (transactive response DNA binding protein 43), which encodes TDP-43 (TAR DNA-binding protein 43). A mutation in exon 6 of TARDBP causes the aminoacidic substitution G376D in the C-terminal region of TDP-43, leading to its cytoplasmic mislocalization and aggregation. In fibroblasts derived from patients carrying this mutation, we found a strong increase in lysosome number, with overexpression and higher nuclear translocation of the transcription factor TFEB. In contrast, lysosomal functionality was deeply compromised. Interestingly, lysosomal activity was unaffected at an early stage of the disease, worsening in more advanced stages. Moreover, we observed the same pathological phenotype in iPSC (induced pluripotent stem cells)-derived patient motor neurons carrying the G376D mutation. Therefore, this mutation compromises the functionality of lysosomes, possibly contributing to neurodegeneration.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*Lysosomes/metabolism/pathology
*DNA-Binding Proteins/genetics/metabolism
Motor Neurons/metabolism/pathology
*Mutation
Fibroblasts/metabolism/pathology
Male
Female
Induced Pluripotent Stem Cells/metabolism
Middle Aged

@article {pmid40243463,
year = {2025},
author = {Fan, X and Diao, W and Wang, H and Yin, X and Qian, W},
title = {Interferon Regulatory Factors as a Potential Therapeutic Target for Neuroinflammation: A Focus on Alzheimer's Disease.},
journal = {International journal of molecular sciences},
volume = {26},
number = {7},
pages = {},
doi = {10.3390/ijms26072906},
pmid = {40243463},
issn = {1422-0067},
support = {82473926//National Natural Science Foundation of China/ ; 81872875//National Natural Science Foundation of China/ ; 81170317//National Natural Science Foundation of China/ ; 81473218//National Natural Science Foundation of China/ ; 81503077//National Natural Science Foundation of China/ ; JC2023042//the project of Nantong Natural Science Foundation/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/drug therapy/pathology ; Animals ; *Interferon Regulatory Factors/metabolism/genetics ; *Neuroinflammatory Diseases/metabolism/drug therapy ; Signal Transduction ; Inflammation/metabolism ; },
abstract = {Interferon Regulatory Factors (IRFs) are critical modulators of immune and inflammatory responses, yet their roles in Alzheimer's disease (AD) and other neurodegenerative disorders remain incompletely understood. While IRFs are recognized for their regulatory functions in neuroinflammation, microglial activation, and neuronal survival, their dual roles as both drivers of pathological inflammation and mediators of neuroprotective pathways underscore a sophisticated regulatory paradox in neurodegenerative disorders. This review aims to synthesize current evidence on IRF-mediated neuroinflammation in AD and related diseases, focusing on the multifaceted functions of key IRF family members, including IRF1, IRF3, and IRF7. We critically evaluate their divergent roles: IRF1 and IRF3, for instance, exacerbate neuroinflammatory cascades and amyloid-beta (Aβ) pathology in AD, whereas IRF7 may paradoxically suppress inflammation under specific conditions. Additionally, we explore IRF dysregulation in Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease, emphasizing shared and distinct mechanisms across neurodegenerative disorders. Restoring IRF balance through genetic manipulation, small-molecule inhibitors, or microbiome-derived modulators could attenuate neuroinflammation, enhance Aβ clearance, and protect neuronal integrity. Ultimately, this work provides a framework for future research to harness IRF signaling pathways in the development of precision therapies for AD and other neurodegenerative diseases.},
}

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

@article {pmid40241787,
year = {2025},
author = {Wölfel, SM and Widmann, CN and Castro-Gomez, S and Weydt, P and Tacik, P and Heneka, MT},
title = {Cognitive capacity in amyotrophic lateral sclerosis: the value of diagnostic markers in cerebrospinal fluid and the influence of nutrition and pulmonary function.},
journal = {Brain communications},
volume = {7},
number = {2},
pages = {fcaf137},
pmid = {40241787},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis is an incurable neurodegenerative disease that is fatal with a median of 3-4 years. It is characterized by degeneration of the first and second motor neurons. In addition to physical limitations, neuropsychological abnormalities occur in more than 50% of cases. This leads to a rapid loss of autonomy and increases the need for care. An individual prognosis for the course of the disease, in particular the development of cognitive and behavioural abnormalities, is not yet possible As part of our investigations, we focused on cognitive performance and behavioural abnormalities measured by the Edinburgh Cognitive and Behavioural ALS Screen in patients with amyotrophic lateral sclerosis and investigated possible prognostic biomarkers in cerebrospinal fluid as well as modifiable factors such as nutrition and lung function. A retrospective data analysis of 99 patients with amyotrophic lateral sclerosis cases examined between 2018 and 2021 at the Department for Neurodegenerative Diseases and Gerontopsychiatry at the University Hospital of Bonn, using Edinburgh Cognitive and Behavioural ALS Screen, revealed that elevated levels of total tau and phospho-tau 181 were associated with diminished performance of patients with amyotrophic lateral sclerosis on the Edinburgh Cognitive and Behavioural ALS Screen. Additionally, weight loss during the course of the disease has been observed to have a deleterious impact on cognitive performance. Moreover, we were able to demonstrate a previously insufficiently described correlation between abnormalities in the Edinburgh Cognitive and Behavioural ALS Screen and low-normal thiamine levels in serum. The hypothesis that reduced lung function has a negative effect on cognitive performance was not supported by our findings. The initial onset of amyotrophic lateral sclerosis, whether bulbar or spinal, does not appear to affect cognition and behaviour measured using Edinburgh Cognitive and Behavioural ALS Screen. Furthermore, our findings confirm the utility of the Edinburgh Cognitive and Behavioural ALS Screen in identifying a behavioural variant frontotemporal dementia in amyotrophic lateral sclerosis patients who have been previously diagnosed by experienced neurologists using the Rascovsky criteria. This development facilitates a more precise utilization of complex diagnostic instruments. Our results provide insight into the prognosis of patients with amyotrophic lateral sclerosis in terms of cognitive performance and behavioural abnormalities as the disease progresses, as well as potential therapeutic approaches to stabilize and support neuropsychological abnormalities. The importance of total tau as a widely available prognostic marker should be emphasized. Additionally, new avenues of research are emerging, particularly regarding the role of thiamine in amyotrophic lateral sclerosis.},
}

@article {pmid40241786,
year = {2025},
author = {Hernández-Gloria, JJ and Jaramillo-Gonzalez, A and Savić, AM and Mrachacz-Kersting, N},
title = {Toward brain-computer interface speller with movement-related cortical potentials as control signals.},
journal = {Frontiers in human neuroscience},
volume = {19},
number = {},
pages = {1539081},
pmid = {40241786},
issn = {1662-5161},
abstract = {Brain Computer Interface spellers offer a promising alternative for individuals with Amyotrophic Lateral Sclerosis (ALS) by facilitating communication without relying on muscle activity. This study assessed the feasibility of using movement related cortical potentials (MRCPs) as a control signal for a Brain-Computer Interface speller in an offline setting. Unlike motor imagery-based BCIs, this study focused on executed movements. Fifteen healthy subjects performed three spelling tasks that involved choosing specific letters displayed on a computer screen by performing a ballistic dorsiflexion of the dominant foot. Electroencephalographic signals were recorded from 10 sites centered around Cz. Three conditions were tested to evaluate MRCP performance under varying task demands: a control condition using repeated selections of the letter "O" to isolate movement-related brain activity; a phrase spelling condition with structured text ("HELLO IM FINE") to simulate a meaningful spelling task with moderate cognitive load; and a random condition using a randomized sequence of letters to introduce higher task complexity by removing linguistic or semantic context. The success rate, defined as the presence of an MRCP, was manually determined. It was approximately 69% for both the control and phrase conditions, with a slight decrease in the random condition, likely due to increased task complexity. Significant differences in MRCP features were observed between conditions with Laplacian filtering, whereas no significant differences were found in single-site Cz recordings. These results contribute to the development of MRCP-based BCI spellers by demonstrating their feasibility in a spelling task. However, further research is required to implement and validate real-time applications.},
}

@article {pmid40180127,
year = {2025},
author = {Kaltchenko, M and Kim, E and Radtke, S and Wan, J},
title = {Response to Li et al's "Comments on 'Dupilumab and neuropsychiatric outcomes in pediatric atopic dermatitis: A real-world cohort analysis'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.03.081},
pmid = {40180127},
issn = {1097-6787},
}

@article {pmid40240969,
year = {2025},
author = {Xia, H and Wang, ZH and Wang, XB and Gao, MR and Jiang, S and Du, XY and Yang, XL},
title = {Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseases.},
journal = {BMC neurology},
volume = {25},
number = {1},
pages = {160},
pmid = {40240969},
issn = {1471-2377},
support = {2023B03003//Autonomous Region Key Research and Development Project/ ; 2022TSYCLJ0066//the Tian-Shan Talent Program/ ; 82371258//the National Natural Science Foundation of China/ ; ZYYD2022C17//the Central Guiding Local Science and Technology Development Special Fund Project/ ; },
abstract = {OBJECTIVE: This study aims to investigate the causal relationship between Mitochondrial DNA (mtDNA) copy number and several common neurodegenerative diseases (NDs).

METHODS: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS) as instrumental variables (IVs). After screening for relevance and potential confounders, we estimated the association between mtDNA copy number and NDs, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS). Additionally, we validated our findings using GWAS data on mtDNA copy number from Longchamps et al., sourced from the Genetics Epidemiology Consortium and the UK Biobank (UKB) aging study cohort.

RESULTS: A GWAS analysis of 395,718 UKB participants found no significant association between mtDNA copy number and the risk of NDs, including AD (OR = 0.956, P = 0.708), PD (OR = 1.223, P = 0.179), ALS (OR = 0.972, P = 0.374), and MS (OR = 0.932, P = 0.789). Similarly, reverse MR analysis revealed no significant relationship between genetic predictions of NDs and mtDNA copy number: AD (OR = 0.987, P = 0.062), PD (OR = 0.997, P = 0.514), ALS (OR = 0.974, P = 0.706), and MS (OR = 1.003, P = 0.181).

CONCLUSION: Although mitochondrial dysfunction is implicated in the pathogenesis of NDs, no clear evidence supports a causal role for mtDNA copy number. The relationship between mtDNA copy number and NDs is likely mediated by more complex molecular regulatory mechanisms. Further research is required to elucidate these intricate interactions.},
}

@article {pmid40238886,
year = {2025},
author = {Cheemala, A and Kimble, AL and Burrage, EN and Helming, SB and Tyburski, JD and Leclair, NK and Omar, OM and Zuberi, AR and Murphy, M and Jellison, ER and Reese, B and Hu, X and Lutz, CM and Yan, R and Murphy, PA},
title = {Amyotrophic lateral sclerosis and frontotemporal dementia mutation reduces endothelial TDP-43 and causes blood-brain barrier defects.},
journal = {Science advances},
volume = {11},
number = {16},
pages = {eads0505},
doi = {10.1126/sciadv.ads0505},
pmid = {40238886},
issn = {2375-2548},
mesh = {*Blood-Brain Barrier/metabolism/pathology ; *DNA-Binding Proteins/genetics/metabolism ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *Frontotemporal Dementia/genetics/metabolism/pathology ; Mice ; *Mutation ; Humans ; *Endothelial Cells/metabolism/pathology ; Disease Models, Animal ; Brain/metabolism/pathology ; },
abstract = {Mutations in the TARDBP gene encoding TDP-43 protein are linked to loss of function in neurons and familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We recently identified reduced nuclear TDP-43 in capillary endothelial cells (ECs) of donors with ALS-FTD. Because blood-brain barrier (BBB) permeability increases in ALS-FTD, we postulated that reduced nuclear TDP-43 in ECs might contribute. Here, we show that nuclear TDP-43 is reduced in ECs of mice with an ALS-FTD-associated mutation in TDP-43 (Tardbp[G348C]) and that this leads to cell-autonomous loss of junctional complexes and BBB integrity. Targeted excision of TDP-43 in brain ECs recapitulates BBB defects and loss of junctional complexes and ultimately leads to fibrin deposition, gliosis, phospho-Tau accumulation, and impaired memory and social interaction. Transcriptional changes in TDP-43-deficient ECs resemble diseased brain ECs. These data show that nuclear loss of TDP-43 in brain ECs disrupts the BBB and causes hallmarks of FTD.},
}

*Blood-Brain Barrier/metabolism/pathology
*DNA-Binding Proteins/genetics/metabolism
Animals
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*Frontotemporal Dementia/genetics/metabolism/pathology
Mice
*Mutation
Humans
*Endothelial Cells/metabolism/pathology
Disease Models, Animal
Brain/metabolism/pathology

@article {pmid40237254,
year = {2025},
author = {Russek, M and Peltner, J and Haenisch, B},
title = {Supplementing Single-Arm Trials with External Control Arms-Evaluation of German Real-World Data.},
journal = {Clinical pharmacology and therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1002/cpt.3684},
pmid = {40237254},
issn = {1532-6535},
abstract = {As single-arm trials (SATs) are increasingly used in pharmaceutical research, the validity of such study designs needs to be critically assessed. We characterize the feasibility of supplementing SATs with real-world data (RWD)-derived external control arms by determining the proportion of SATs on breast cancer and amyotrophic lateral sclerosis (ALS) for which an external control arm based on RWD can be constructed. The main outcome measure is the number and percentage of trials for which all important eligibility criteria and at least one primary endpoint could be identified in one of five German RWD sources. We surveyed all SATs concerning breast cancer or ALS treatment registered in the European Union's clinical trial registers between 2004 and 2023. Ten out of 379 breast cancer SATs and 2 of 11 ALS SATs could feasibly be supplemented with RWD-derived external control arms, if all important eligibility criteria and a primary endpoint have to be identifiable in the RWD source. Ninety-three breast cancer trials had at least one outcome ascertainable in a RWD source, and 35 trials had all important eligibility criteria recorded in a RWD source. Nine ALS trials had at least one primary endpoint ascertainable in RWD sources, and 2 had all important eligibility criteria recorded in a RWD source. Our study shows that SATs with RWD-derived external control arms will rarely be suitable to establish treatment effects of medicines in the current setting for the investigated phenotypes and that SATs should be designed with limitations of the source of external controls in mind.},
}

@article {pmid40237114,
year = {2025},
author = {Thompson, OL and Russell, JA and Stockman, SK and Swall, JL and Simmons, T},
title = {Assessing the effectiveness of alternate light sources in the search for skeletal remains.},
journal = {Journal of forensic sciences},
volume = {},
number = {},
pages = {},
doi = {10.1111/1556-4029.70049},
pmid = {40237114},
issn = {1556-4029},
abstract = {Many search and recovery operations for human skeletal remains are unsuccessful due to difficulties recognizing bones in outdoor environments even when evidence indicates the last known whereabouts of missing individuals. Though the collagen component of bone is known to emit fluorescence, this property has not been leveraged consistently during skeletal remains searches. Thirty-six mock searches were completed in 5000 ft[2] zones of eastern deciduous forest by volunteers associated with the Virginia Department of Emergency Management. Pig and deer bones were scattered and partially concealed under brush and leaf cover. Pairs of volunteers were allowed up to 1 h to conduct searches in their usual pattern. Nighttime searches were conducted with handheld alternate light source (ALS) devices (uvBeast™, Crime-lite[®], ForenScope, and Labino AB), which produced ultraviolet (385-395 nm), violet (395-425 nm), blue (~455 nm), cyan (~510 nm), or green (~530 nm) lights. Filtered safety glasses were paired with appropriate ALS. Daytime searches were conducted under the same parameters, without ALS. Results indicated that (1) nighttime searches with ALS produced a recovery rate more than triple that of daytime searches (p < 0.0001) and that they were often completed more quickly, and (2) the violet Crime-lite[®], due to breadth of illumination and strength of fluorescent response, consistently produced the highest recovery rate (95%). Data suggest that nighttime searches with ALS can be used both as the primary search method for locating and recovering human skeletal remains, and as a secondary method for recovering any bones expected to be present but not found during daylight searches.},
}

@article {pmid40236412,
year = {2025},
author = {Jude, JJ and Levi-Aharoni, H and Acosta, AJ and Allcroft, SB and Nicolas, C and Lacayo, BE and Card, NS and Wairagkar, M and Brandman, DM and Stavisky, SD and Willett, FR and Williams, ZM and Simeral, JD and Hochberg, LR and Rubin, DB},
title = {An intuitive, bimanual, high-throughput QWERTY touch typing neuroprosthesis for people with tetraplegia.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.04.01.25324990},
pmid = {40236412},
abstract = {Recognizing keyboard typing as a familiar, high information rate communication paradigm, we developed an intracortical brain computer interface (iBCI) typing neuroprosthesis providing bimanual QWERTY keyboard functionality for people with paralysis. Typing with this iBCI involves only attempted finger movements, which are decoded accurately with as few as 30 calibration sentences. Sentence decoding is improved using a 5-gram language model. This typing neuroprosthesis performed well for two iBCI clinical trial participants with tetraplegia - one with ALS and one with spinal cord injury. Typing speed is user-regulated, reaching 110 characters per minute, resulting in 22 words per minute with a word error rate of 1.6%. This resembles able-bodied typing accuracy and provides higher throughput than current state-of-the-art hand motor iBCI decoding. In summary, a typing neuroprosthesis decoding finger movements, provides an intuitive, familiar, and easy-to-learn paradigm for individuals with impaired communication due to paralysis.},
}

@article {pmid40236149,
year = {2025},
author = {Strell, P and Waldron, MA and Johnson, S and Shetty, A and Crane, AT and Steer, CJ and Low, WC},
title = {Characterization of the intraspecies chimeric mouse brain at embryonic day 12.5.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.03.31.646380},
pmid = {40236149},
issn = {2692-8205},
abstract = {Incidence of neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis have increased dramatically as life expectancy at birth has risen year-over-year and the population ages. Neurological changes within the central nervous system, specifically the brain, include cell loss and deterioration that impact motor function, memory, executive function, and mood. Available treatments are limited and often only address symptomatic manifestations of the disease rather than disease progression. Cell transplantation therapy has shown promise for treating neurodegenerative diseases, but a source of autologous cells is required. Blastocyst complementation provides an innovative method for generating those autologous neural cells. By injecting mouse induced pluripotent stem cells (iPSCs) into a wild type (WT) mouse blastocyst, we generated a chimeric mouse brain derived of both donor and host neuronal and non-neuronal cells. An embryonic day 12.5 (E12.5), automated image analysis of mouse-mouse chimeric brains showed the presence of GFP-labeled donor-derived dopaminergic and serotonergic neuronal precursors. GFP-labeled donor-derived cholinergic precursor neurons and non-neuronal microglia-like and macrophage-like cells were also observed using more conventional imaging analysis software. This work demonstrates that the generation of mouse-mouse chimeric neural cells is possible; and that characterization of early neuronal and non-neuronal precursors provides a first step towards utilizing these cells for cell transplantation therapies for neurodegenerative diseases.},
}

@article {pmid40235960,
year = {2025},
author = {Basgaran, A and Lymberopoulos, E and Burchill, E and Reis-Dehabadi, M and Sharma, N},
title = {Machine learning determines the incidence of Alzheimer's disease based on population gut microbiome profile.},
journal = {Brain communications},
volume = {7},
number = {2},
pages = {fcaf059},
pmid = {40235960},
issn = {2632-1297},
abstract = {The human microbiome is a complex and dynamic community of microbes, thought to have symbiotic benefit to its host. Influences of the gut microbiome on brain microglia have been identified as a potential mechanism contributing to neurodegenerative diseases, such as Alzheimer's disease, motor neurone disease and Parkinson's disease (Boddy SL, Giovannelli I, Sassani M, et al. The gut microbiome: A key player in the complexity of amyotrophic lateral sclerosis (ALS). BMC Med. 2021;19(1):13). We hypothesize that population level differences in the gut microbiome will predict the incidence of Alzheimer's disease using machine learning methods. Cross-sectional analyses were performed in R, using two large, open-access microbiome datasets (n = 959 and n = 2012). Countries in these datasets were grouped based on Alzheimer's disease incidence and the gut microbiome profiles compared. In countries with a high incidence of Alzheimer's disease, there is a significantly lower diversity of the gut microbiome (P < 0.05). A permutational analysis of variance test (P < 0.05) revealed significant differences in the microbiome profile between countries with high versus low incidence of Alzheimer's disease with several contributing taxa identified: at a species level Escherichia coli, and at a genus level Haemophilus and Akkermansia were found to be reproducibly protective in both datasets. Additionally, using machine learning, we were able to predict the incidence of Alzheimer's disease within a country based on the microbiome profile (mean area under the curve 0.889 and 0.927). We conclude that differences in the microbiome can predict the varying incidence of Alzheimer's disease between countries. Our results support a key role of the gut microbiome in neurodegeneration at a population level.},
}

@article {pmid40235867,
year = {2025},
author = {Sundararaju, U and Rajakumar, HK},
title = {Prognostic value of neutrophil-to-lymphocyte ratio in gastric cancer: Enhancing clinical relevance.},
journal = {World journal of gastrointestinal oncology},
volume = {17},
number = {4},
pages = {103128},
pmid = {40235867},
issn = {1948-5204},
abstract = {Gastric cancer (GC) is a leading cause of cancer-related deaths, highlighting the need for reliable prognostic biomarkers to guide treatment. Wei et al's systematic review and meta-analysis evaluates the neutrophil-to-lymphocyte ratio (NLR) as a potential biomarker for GC patients undergoing neoadjuvant chemotherapy. NLR is a simple and cost-effective measure of systemic inflammation that shows promise in predicting treatment response and survival outcomes, including overall survival and progression-free survival. However, variations in NLR thresholds and timing of measurements affect its accuracy and clinical utility. Moreover, the studies reviewed primarily involved Asian populations, which may limit the generalizability of the findings. To improve NLR's clinical relevance, future research should focus on standardizing NLR thresholds, refining measurement timing, and incorporating additional inflammatory markers like platelet-to-lymphocyte ratio and Glasgow prognostic score. Addressing confounders and including diverse patient populations will help improve NLR's reliability as a prognostic marker for GC.},
}

@article {pmid40235786,
year = {2025},
author = {Wang, LP and Yang, C and Fu, JY and Zhang, XY and Shen, XM and Shi, NL and Wu, HL and Gao, XR},
title = {A preliminary study of steady-state visually-evoked potential-based non-invasive brain-computer interface technology as a communication aid for patients with amyotrophic lateral sclerosis.},
journal = {Quantitative imaging in medicine and surgery},
volume = {15},
number = {4},
pages = {3469-3479},
pmid = {40235786},
issn = {2223-4292},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to severe disability and ultimately death. Communication difficulties are common in ALS patients as the disease progresses; thus, alternative communication aids need to be explored. This study sought to examine the use and effect of steady-state visually-evoked potential (SSVEP)-based non-invasive brain-computer interface (BCI) technology as a communication aid for patients with ALS and to examine possible influencing factors.

METHODS: In total, 12 patients with ALS were selected, and a 40-character target selection was performed using SSVEP-based non-invasive BCI technology. The patients were presented with specific visual stimuli, and nine-lead electroencephalogram (EEG) signals in the occipital region were acquired when the patients were looking at the target. Using the feature recognition analysis method, the final output was the characters recognized by the patients. The basic clinical data of the patients (e.g., age, gender, course of disease, affected area, and ALS functional scale score) were collected, and the BCI accuracy rate, information transmission rate, and average SSVEP recognition time were calculated.

RESULTS: The results revealed that the recognition efficiency of the ALS patients varied. The accuracy potential increased as the stimulus duration extended, highlighting the possibility for improvement via further optimization. The results also showed that the experimental design schedules typically used for healthy individuals may not be entirely suitable for ALS patients, which presents an exciting opportunity to tailor future studies to better meet the unique needs of ASL patients. Further, the results revealed the necessity of using customized experimental schedules in future studies, which could lead to more relevant and effective data collection for ALS patients.

CONCLUSIONS: The study found that SSVEP-based non-invasive BCI technology has promising potential as a communication aid for ALS patients. While further algorithm optimization and comprehensive studies with larger sample sizes are necessary, the initial findings are encouraging, and could lead to the development of more effective communication solutions that are specifically tailored to address the challenges faced by ALS patients.},
}

@article {pmid40235752,
year = {2025},
author = {Huang, NX and Zeng, JY and Huang, HW and Fang, SY and Chen, S and Li, JQ and Chen, HJ and Zou, ZY},
title = {Association of glymphatic system disturbance with neural dysfunction in amyotrophic lateral sclerosis.},
journal = {Quantitative imaging in medicine and surgery},
volume = {15},
number = {4},
pages = {3445-3457},
pmid = {40235752},
issn = {2223-4292},
abstract = {BACKGROUND: Formation and aggregation of pathological proteins in the brain constitutes a critical hallmark of amyotrophic lateral sclerosis (ALS). However, the role of the glymphatic system in the clearance of pathological proteins in ALS remains unclear. The purpose of this cross-sectional study was to evaluate glymphatic system disturbance in ALS and its relation to neural function.

METHODS: This study included 38 healthy controls (HCs) and 30 patients with ALS who underwent diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI). The disease severity, duration, and progression rate of ALS were recorded. Glymphatic system function was indirectly evaluated by DTI analysis along the perivascular space (ALPS) surrounding the deep medullary vein. Neural activity was examined in sensorimotor-related brain areas by measuring amplitude of low-frequency fluctuation (ALFF) based on rs-fMRI. A two-sample t-test or Mann-Whitney test was used to examine between-group differences in ALPS, diffusivities measured along the x-, y-, and z-axis in the association (Dxx_association, Dyy_association, Dzz_association) and projection (Dxx_projection, Dyy_projection, Dzz_projection) fiber areas, and ALFF indices. The associations between ALPS, diffusivities, ALFF, and clinical assessments were determined via Spearman correlation analysis, and diagnostic performance was evaluated with receiver operating characteristic curve analysis.

RESULTS: Patients with ALS exhibited significantly decreased ALPS and increased diffusivities (Dyy_association and Dyy_projection) as compared to HCs (all P values <0.05). Patients with ALS showed decreased ALFF in sensorimotor-related regions, including the bilateral primary motor and somatosensory areas (all P values <0.001) and left supplementary motor area (P=0.031). ALPS and diffusivities were correlated with ALFF in the sensorimotor-motor regions (all P values <0.05), and ALPS and ALFF correlated with disease severity and duration (all P values <0.05). ALPS, diffusivities, and ALFF showed moderate ability to diagnose ALS.

CONCLUSIONS: The glymphatic system function was impaired in ALS. This may contribute to spontaneous neural activity disturbance and could represent a mechanism for the development of sensorimotor deficits frequently observed in patients with ALS.},
}

@article {pmid40235273,
year = {2025},
author = {Scelsa, SN and MacGowan, DJL},
title = {Disease Modification in SOD1-ALS With Tofersen May Result in Serious CNS Inflammation.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.28413},
pmid = {40235273},
issn = {1097-4598},
}

@article {pmid40234983,
year = {2025},
author = {Xie, Q and Li, K and Chen, Y and Li, Y and Jiang, W and Cao, W and Yu, H and Fan, D and Deng, B},
title = {Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.},
journal = {Translational neurodegeneration},
volume = {14},
number = {1},
pages = {19},
pmid = {40234983},
issn = {2047-9158},
support = {81901273//National Natural Science Foundation of China/ ; ZCLY24H0903//Natural Science Foundation of Zhejiang Province/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that remains incurable. Although the etiologies of ALS are diverse and the precise pathogenic mechanisms are not fully understood, approximately 20% of ALS cases are caused by genetic factors. Therefore, advancing targeted gene therapies holds significant promise, at least for the 20% of ALS patients with genetic etiologies. In this review, we summarize the main strategies and techniques of current ALS gene therapies based on ALS risk genes, and review recent findings from animal studies and clinical trials. Additionally, we highlight ALS-related genes with well-understood pathogenic mechanisms and the potential of numerous emerging gene-targeted therapeutic approaches for ALS.},
}

@article {pmid40234916,
year = {2025},
author = {Park, KH and Yu, E and Choi, S and Kim, S and Park, C and Lee, JE and Kim, KW},
title = {Optogenetic induction of TDP-43 aggregation impairs neuronal integrity and behavior in Caenorhabditis elegans.},
journal = {Translational neurodegeneration},
volume = {14},
number = {1},
pages = {20},
pmid = {40234916},
issn = {2047-9158},
support = {NRF-2022R1A2C1003766//Ministry of Education, Science and Technology/ ; RS-2024-00331685//Ministry of Food and Drug Safety/ ; },
abstract = {BACKGROUND: Cytoplasmic aggregation of TAR DNA binding protein 43 (TDP-43) in neurons is one of the hallmarks of TDP-43 proteinopathy. Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are closely associated with TDP-43 proteinopathy; however, it remains uncertain whether TDP-43 aggregation initiates the pathology or is a consequence of it.

METHODS: To demonstrate the pathology of TDP-43 aggregation, we applied the optoDroplet technique in Caenorhabditis elegans (C. elegans), which allows spatiotemporal modulation of TDP-43 phase separation and assembly.

RESULTS: We demonstrate that optogenetically induced TDP-43 aggregates exhibited insolubility similar to that observed in TDP-43 proteinopathy. These aggregates increased the severity of neurodegeneration, particularly in GABAergic motor neurons, and exacerbated sensorimotor dysfunction in C. elegans.

CONCLUSIONS: We present an optogenetic C. elegans model of TDP-43 proteinopathy that provides insight into the neuropathological mechanisms of TDP-43 aggregates. Our model serves as a promising tool for identifying therapeutic targets for TDP-43 proteinopathy.},
}

@article {pmid40234116,
year = {2025},
author = {McHale-Owen, H and Faller, KME and Chaytow, H and Gillingwater, TH},
title = {Phosphoglycerate kinase 1 as a therapeutic target in neurological disease.},
journal = {Trends in molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molmed.2025.03.008},
pmid = {40234116},
issn = {1471-499X},
abstract = {Phosphoglycerate kinase 1 (PGK1) is a highly conserved enzyme that catalyzes the initial ATP-producing step in glycolysis. Improving cellular energy production by increasing PGK1 activity may be beneficial in multiple neurological conditions where cell metabolism is dysregulated, including Parkinson's disease (PD) and motor neuron disease (MND). This review examines recent evidence that suggests increasing PGK1 activity may be beneficial in multiple neurological conditions and discusses the current challenges surrounding the development of PGK1-focused therapies. PGK1 has considerable therapeutic potential, but novel PGK1 activators are needed to maximize the benefit for patients.},
}

@article {pmid40232694,
year = {2024},
author = {Ichikawa, Y and Sato, B and Hirano, SI and Takefuji, Y and Satoh, F},
title = {Hydrogen inhalation therapy may ameliorate amyotrophic lateral sclerosis.},
journal = {Medical gas research},
volume = {14},
number = {3},
pages = {149-150},
doi = {10.4103/2045-9912.390249},
pmid = {40232694},
issn = {2045-9912},
}

@article {pmid40232582,
year = {2025},
author = {Mehrnoosh, F and Rezaei, D and Pakmehr, SA and Nataj, PG and Sattar, M and Shadi, M and Ali-Khiavi, P and Zare, F and Hjazi, A and Al-Aouadi, RFA and Sapayev, V and Zargari, F and Alkhathami, AG and Ahmadzadeh, R and Khedmatgozar, M and Hamzehzadeh, S},
title = {The role of Panax ginseng in neurodegenerative disorders: mechanisms, benefits, and future directions.},
journal = {Metabolic brain disease},
volume = {40},
number = {4},
pages = {183},
pmid = {40232582},
issn = {1573-7365},
mesh = {Humans ; *Panax ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Ginsenosides/therapeutic use/pharmacology ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Plant Extracts/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; },
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS), and Huntington's disease (HD) represent a growing global health challenge, especially with aging populations. Characterized by progressive neuronal loss, these diseases lead to cognitive, motor, and behavioral impairments, significantly impacting patients' quality of life. Current therapies largely address symptoms without halting disease progression, underscoring the need for innovative, disease-modifying treatments. Ginseng, a traditional herbal medicine with well-known adaptogenic and neuroprotective properties, has gained attention as a potential therapeutic agent for neurodegeneration. Rich in bioactive compounds called ginsenosides, ginseng exhibits antioxidant, anti-inflammatory, and anti-apoptotic effects, making it a promising candidate for addressing the complex pathology of neurodegenerative diseases. Recent studies demonstrate that ginsenosides modulate disease-related processes such as oxidative stress, protein aggregation, mitochondrial dysfunction, and inflammation. In AD models, ginsenosides have been shown to reduce amyloid-beta accumulation and tau hyperphosphorylation, while in PD, they help protect dopaminergic neurons and mitigate motor symptoms. Ginseng's effects in ALS, MS, and HD models include improving motor function, extending neuronal survival, and reducing cellular toxicity. This review provides a comprehensive overview of the neuroprotective mechanisms of ginseng, emphasizing its therapeutic potential across various neurodegenerative diseases and discussing future research directions for its integration into clinical practice.},
}

Humans
*Panax
*Neurodegenerative Diseases/drug therapy/metabolism
Animals
*Ginsenosides/therapeutic use/pharmacology
*Neuroprotective Agents/therapeutic use/pharmacology
*Plant Extracts/therapeutic use/pharmacology
Oxidative Stress/drug effects

@article {pmid40232308,
year = {2025},
author = {Wu, J and Xu, Y and Yin, T and Zhang, N and Fan, D and Ye, S},
title = {Unveiling structural damage of the corpus callosum in amyotrophic lateral sclerosis through diffusion tensor imaging and spread direction perspectives.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2490822},
doi = {10.1080/07853890.2025.2490822},
pmid = {40232308},
issn = {1365-2060},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/physiopathology ; *Corpus Callosum/pathology/diagnostic imaging ; *Diffusion Tensor Imaging/methods ; Male ; Female ; Middle Aged ; Aged ; Adult ; Motor Cortex/pathology/diagnostic imaging ; },
abstract = {OBJECTIVE: Damage to the corpus callosum (CC) in amyotrophic lateral sclerosis (ALS) patients has been confirmed via electrophysiological, neuroimaging, and autopsy studies. Additionally, the CC is hypothesized to serve as a pathway for the spread of pathological information. This study aimed to investigate whether the CC plays a mediating role in the symptomatic spread of ALS.

METHODS: In this observational study, diffusion tensor imaging (DTI) data were acquired from 45 individuals with the upper motor neuron-dominant (UMN-D) phenotype of ALS. The UMN-D ALS patients were categorized into two groups based on the direction of symptom spread, including 25 patients with horizontal spread (group H) and 20 patients with vertical spread (group V). Diffusivity indices were derived through whole-brain analysis and probabilistic fiber tracking.

RESULTS: According to the voxel-based analysis and tract-based spatial statistics, differences in axial diffusivity (AD) in the CC were observed between disease subgroups, with patients in group H showing higher AD values than those in group V. Fiber tracking analysis revealed persistent differences in the AD indices of CC-primary motor cortex (PMC) fibers between the two disease subgroups.

CONCLUSION: In UMN-D ALS patients, the direction of symptom spread may be related to the degree of CC involvement. The AD metric may be a more specific indicator of CC damage.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/physiopathology
*Corpus Callosum/pathology/diagnostic imaging
*Diffusion Tensor Imaging/methods
Male
Female
Middle Aged
Aged
Adult
Motor Cortex/pathology/diagnostic imaging

@article {pmid40231507,
year = {2025},
author = {Tecalco-Cruz, AC and Ramírez-Jarquín, JO and Medina Abreu, KH and Palacios-Serrato, EG and López-Cánovas, L and Zepeda-Cervantes, J and Oropeza-Martínez, E},
title = {Molecular Interplay of ISG15/ISGylation in Neuropathologies.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273378149250322050004},
pmid = {40231507},
issn = {1996-3181},
abstract = {ISG15 is a 15 kDa ubiquitin-like protein that covalently associates with its target proteins by a sequential enzymatic process known as ISGylation. Research on protein ISGylation has increased in recent years, and some studies have suggested that ISG15 is involved in neuroprotection and neurodegeneration mechanisms. This review outlines the current state of research on the implications of ISG15/ISGylation in other neuropathies such as malignant tumors, ataxia telangiectasia, ischemia, depression, and neurodegenerative diseases such as Alzheimer´s, Parkinson's diseases, multiple sclerosis, and amyotrophic lateral sclerosis. Based on the studies reported to date, ISG15/ ISGylation promotes the progression of brain tumors such as glioblastoma. Moreover, ISG15/ ISGylation seems to play a dual role in neuropathies, demonstrating a neuroprotective effect when there is acute brain damage, but ISG15/ISGylation is associated with reduced neuroprotection when there is chronic damage, such as in neurodegenerative diseases.},
}

@article {pmid40231293,
year = {2025},
author = {Smyth, BR and Patwardhan, S and Turner, EL and McLintock, S},
title = {Using Functional Resonance Analysis Method (FRAM) Modelling to Assess the Factors That Slow or Prevent Clinicians in Performing Advanced Life Support (ALS) During Crash Calls to Park House Mental Health Hospital.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e82231},
pmid = {40231293},
issn = {2168-8184},
abstract = {This Quality Improvement Project (QIP) aimed to improve the response system for crash calls at Park House Mental Health Hospital, supported by the North Manchester General Hospital Crash Team. Using a functional resonance analysis method (FRAM), the team identified inefficiencies in the Advanced Life Support (ALS) process, with delayed responses increasing patient mortality risks. Interviews with staff helped create "work-as-imagined" (WAI) and "work-as-done" (WAD) models, highlighting the underperformed functions like ward entry protocols, and fully stocked crash trolleys. Recommendations, including access cards, stock changes, and live simulations, were implemented, in an aim to improve ALS provision.},
}

@article {pmid40230758,
year = {2025},
author = {Bossei, AA and Al Zahrani, HA and Bossei, FA and Saadi, SM and Alsaedi, AS and Al Sulami, AQ and Al Asmari, EH and Aalam, AA and Khojah, IM},
title = {Emergency Physicians' Perceptions, Knowledge, and Attitudes Toward Family Presence During Resuscitation in the Emergency Department: A Multicenter Survey-Based Cross-Sectional Study.},
journal = {Cureus},
volume = {17},
number = {3},
pages = {e80612},
pmid = {40230758},
issn = {2168-8184},
abstract = {BACKGROUND: Cardiac arrest remains a significant public health issue, with high incidence rates in both in-hospital and out-of-hospital settings. The practice of family presence during resuscitation (FPDR) has gained attention for its potential benefits to patients and their families. This study evaluates the perceptions, knowledge, and attitudes of emergency physicians (EPs) regarding FPDR in the emergency department (ED) and aims to inform policy development at King Abdulaziz University Hospital in Jeddah, Saudi Arabia.

METHODS:  A multicenter cross-sectional study was conducted from January to April 2023, surveying EPs from multiple EDs across the western region of Saudi Arabia. Participants, certified in basic (BLS) or advanced life support (ALS), completed an anonymous online survey adapted from previous studies.

RESULTS: Our study surveyed 122 EPs, with 112 completing the survey. Of the participants, 49.1% were aged 25-29 years, 61.6% were men, and 58.9% had 1-4 years of work experience. Awareness of FPDR was reported by 67.9% (n = 76) of participants. Only 3.6% (n = 4) had a policy allowing FPDR, while 6.3% (n = 7) had a policy prohibiting it. Additionally, 49.1% (n = 55) supported implementing an FPDR policy. Awareness of FPDR was significantly higher among younger, male, and more experienced physicians (p < 0.05). Higher perception and practice scores were observed among those aware of FPDR, those who had participated in CPR with a family member, and those without a prohibiting policy (p < 0.05).

CONCLUSION: EPs in the western region of Saudi Arabia generally support FPDR, recognizing its potential benefits. However, concerns about its impact on performance and medicolegal issues warrant further exploration. To implement effective FPDR policies, these concerns must be addressed, along with efforts to promote awareness and training. Future research should expand to include broader healthcare settings and multidisciplinary teams to develop comprehensive, evidence-based guidelines.},
}

@article {pmid40229738,
year = {2025},
author = {Abdoalsadig, E and Hamid, M and Peck, A and Johar, L and Kimonis, V},
title = {Utilization of CoRDS registry to monitor quality of life in patients with VCP multisystem proteinopathy.},
journal = {Orphanet journal of rare diseases},
volume = {20},
number = {1},
pages = {178},
pmid = {40229738},
issn = {1750-1172},
mesh = {Humans ; Registries ; *Quality of Life ; Female ; Male ; *Valosin Containing Protein/genetics/metabolism ; Middle Aged ; Aged ; Myositis, Inclusion Body/genetics ; Adult ; Amyotrophic Lateral Sclerosis/genetics ; Osteitis Deformans/genetics ; Frontotemporal Dementia/genetics ; },
abstract = {BACKGROUND: VCP disease, also known as multisystem proteinopathy, is a rare, autosomal dominant, adult-onset, neuromuscular disease that is caused by variants in the valosin-containing protein (VCP) gene. VCP disease may exhibit one or more of the following primary features: inclusion body myopathy, Paget's disease of bone (PDB), Frontotemporal dementia, and amyotrophic lateral sclerosis. Due to its progressive nature, death normally occurs in their sixties due to respiratory and cardiac failure. The purpose of this study is to utilize the Cure VCP Disease patient registry hosted by the Coordination of Rare Diseases at Sanford (CoRDS) to conduct a prospective natural history study.

METHODS: Seventy-nine participants enrolled in the patient registry and answered demographic, VCP variant type, Patient-reported outcome measures (PROMs), and quality of life (QOL) questionnaires over the course of 3 years. We additionally investigated if any sex differences existed and if genotype-phenotype correlations affected the rate of progression of the varying clinical manifestations.

RESULTS: Overall, participants' mobility declined significantly as the disease progressed. Participants reported a 0.6% decline in upper extremity function, 1.2% decline in lower extremity function, and 0.3% decline in cognitive function per year of age. Furthermore, participants reported a 1.6% decline in upper and lower extremity function and a 0.1% decline in cognitive function per year of disease duration. The highest PROMs correlations were noted between overall health and lower extremity function, upper extremity function, fatigue, and the ability to perform vigorous activities. Genotype-phenotype correlations revealed no significant differences except for the absence of PDB in the p.Arg159Cys group.

CONCLUSION: The VCP CoRDS Registry was found to be a valuable tool for monitoring the QOL in patients with VCP disease and capturing patient perspectives for future clinical trials.},
}

Humans
Registries
*Quality of Life
Female
Male
*Valosin Containing Protein/genetics/metabolism
Middle Aged
Aged
Myositis, Inclusion Body/genetics
Adult
Amyotrophic Lateral Sclerosis/genetics
Osteitis Deformans/genetics
Frontotemporal Dementia/genetics

@article {pmid40229540,
year = {2025},
author = {Ghimire, S and Kreilaus, F and Rosa Porto, R and Anderson, LL and Yerbury, JJ and Arnold, JC and Karl, T},
title = {Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1[G93 A]) mouse model of amyotrophic lateral sclerosis.},
journal = {Psychopharmacology},
volume = {},
number = {},
pages = {},
pmid = {40229540},
issn = {1432-2072},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the copper-zinc superoxide dismutase 1 (SOD1) mouse model of ALS that carries a G93A mutation (SOD1[G93A]).

METHODS: Male and female SOD1[G93A] and wild type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.

RESULTS: CBD treatment ameliorated the bodyweight loss in female SOD1[G93A] mice, tended to reinstate sociability in SOD1[G93A] males, strengthened social recognition memory in SOD1[G93A] females, and improved the PPI response in younger SOD1[G93A] females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male SOD1[G93A] mice and decreased the acoustic startle response and strengthened cue freezing in male mice.

CONCLUSION: Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of SOD1[G93A] mice in a sex specific manner without altering the motor phenotype.},
}

@article {pmid40229296,
year = {2025},
author = {Kumar, P and Bishnoi, R and Priyadarshini, P and Chhuneja, P and Singla, D},
title = {Understanding the structural basis of ALS mutations associated with resistance to sulfonylurea in wheat.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {12855},
pmid = {40229296},
issn = {2045-2322},
mesh = {*Acetolactate Synthase/genetics/chemistry/metabolism ; *Triticum/genetics/enzymology/drug effects ; *Sulfonylurea Compounds/pharmacology/chemistry ; *Herbicide Resistance/genetics ; Molecular Docking Simulation ; Herbicides/pharmacology ; *Plant Proteins/genetics/chemistry/metabolism ; Molecular Dynamics Simulation ; *Mutation ; Pyridines/pharmacology/chemistry ; },
abstract = {Developing herbicide-tolerant wheat varieties is highly desirable for effective weed management and improved crop yield. The enzyme acetolactate synthase (ALS) is the target enzyme for the sulfonylurea class of herbicides. The structural analysis of mutable sites in ALS is crucial for the generation of herbicide-resistant crops. Previous studies indicated that mutant lines of Triticum aestivum ALS (TaALS) with amino acid substitutions at P174, G631, and G632 residues provided resistance to sulfonylurea herbicide, nicosulfuron. The present study aimed to provide structural insights into mutable residues causing sulfonylurea herbicide resistance to TaALS enzyme through in-silico molecular docking and simulation approaches. The molecular docking analysis suggested a single point mutation at TaALS-P174S, its double mutant conformations (TaALS-G632S/P174S and TaALS-G631D/G632S) and associated triple mutant conformation (TaALS-G631D/G632S/P174S) to have the lowest binding affinity with nicosulfuron than the wild-type conformation of TaALS. Furthermore, the molecular dynamic simulation study confirms the weakest and more stable binding of the triple mutant conformation with nicosulfuron. Our computational study identifies a triple mutant conformation (TaALS-G631D/G632S/P174S) to be more effective in developing sulfonylurea herbicide-resistant wheat crops.},
}

*Acetolactate Synthase/genetics/chemistry/metabolism
*Triticum/genetics/enzymology/drug effects
*Sulfonylurea Compounds/pharmacology/chemistry
*Herbicide Resistance/genetics
Molecular Docking Simulation
Herbicides/pharmacology
*Plant Proteins/genetics/chemistry/metabolism
Molecular Dynamics Simulation
*Mutation
Pyridines/pharmacology/chemistry

@article {pmid40226510,
year = {2025},
author = {Ufarry Alvarado, AJ and Zaidi Pons, MA and Plaza Hernández, J and Torres Ortiz, C},
title = {Improvements of Paraquat Treatment in Liquid Media for Behavior and Neurodegenerative Tests.},
journal = {microPublication biology},
volume = {2025},
number = {},
pages = {},
pmid = {40226510},
issn = {2578-9430},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a disease characterized by misfolded and aggregated proteins that have toxic effects on motor neurons. The missense mutation, G85R, of the sod-1 gene associated with ALS displays locomotor impairments in Caenorhadbitis elegans (C. elegans). We treated the sod-1 (G85R) strain with 0 and 2.5 mM Paraquat treatments in a liquid M9 buffer for 4 hours and in solid NGM media for 18 hours. In both methodologies, the locomotion defects and neurodegeneration were significantly increased with 2.5 mM Paraquat. Our work provides evidence of methodology that is more cost effective, rapid and reproducible to perform behavior and neurodegenerative assay in worms.},
}

@article {pmid40225153,
year = {2023},
author = {Fiorini, MR and Dilliott, AA and Farhan, SMK},
title = {Evaluating the Utility of REVEL and CADD for Interpreting Variants in Amyotrophic Lateral Sclerosis Genes.},
journal = {Human mutation},
volume = {2023},
number = {},
pages = {8620557},
pmid = {40225153},
issn = {1098-1004},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/diagnosis ; *Computational Biology/methods ; *Genetic Predisposition to Disease ; *Genetic Variation ; *Software ; Genetic Association Studies ; Mutation ; Databases, Genetic ; Genetic Testing ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease affecting approximately two per 100,000 individuals globally. While there are many benefits to offering early genetic testing to people with ALS, this has also led to an increase in the yield of novel variants of uncertain significance in ALS-associated genes. Computational (in silico) predictors, including REVEL and CADD, are widely employed to provide supporting evidence of pathogenicity for variants in conjunction with clinical, molecular, and other genetic evidence. However, in silico predictors are developed to be broadly applied across the human genome; thus, their ability to evaluate the consequences of variation in ALS-associated genes remains unclear. To resolve this ambiguity, we surveyed 20 definitive and moderate ClinGen-defined ALS-associated genes from two large, open-access ALS sequencing datasets (total people with ALS = 8,230; controls = 9,671) to investigate REVEL and CADD's ability to predict which variants are most likely to be disease-causing in ALS. While our results indicate a predetermined pathogenicity threshold for REVEL that could be of clinical value for classifying variants in ALS-associated genes, an accurate threshold was not evident for CADD, and both in silico predictors were of limited value for resolving which variants of uncertain significance (VUS) may be likely pathogenic in ALS. Our findings allow us to provide important recommendations for the use of REVEL and CADD scores for variants and indicate that both tools should be used with caution when attempting to evaluate the pathogenicity of VUSs in ALS genetic testing.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/diagnosis
*Computational Biology/methods
*Genetic Predisposition to Disease
*Genetic Variation
*Software
Genetic Association Studies
Mutation
Databases, Genetic
Genetic Testing

@article {pmid40222791,
year = {2025},
author = {Bhardwaj, I and Singh, S and Ansari, AH and Rai, SP and Singh, D},
title = {Effect of stress on neuronal cell: Morphological to molecular approach.},
journal = {Progress in brain research},
volume = {291},
number = {},
pages = {469-502},
doi = {10.1016/bs.pbr.2025.01.010},
pmid = {40222791},
issn = {1875-7855},
mesh = {Humans ; Animals ; *Neurons/pathology/metabolism/physiology ; *Stress, Psychological/pathology/metabolism ; *Brain/pathology ; },
abstract = {Stress can be characterized as any perceived or actual threat that necessitates compensatory actions to maintain homeostasis. It can alter an organism's behavior over time by permanently altering the composition and functionality of brain circuitry. The amygdala and prefrontal cortex are two interrelated brain regions that have been the focus of initial research on stress and brain structural and functional plasticity, with the hippocampus serving as the entry point for most of this knowledge. Prolonged stress causes significant morphological alterations in important brain regions such as the hippocampus, amygdala, and prefrontal cortex. Memory, learning, and emotional regulation are among the cognitive functions that are adversely affected by these changes, including neuronal shrinkage, dendritic retraction, and synaptic malfunction. Stress perturbs the equilibrium of neurotransmitters, neuronal plasticity, and mitochondrial function at the molecular level. On the other hand, chronic stress negatively impacts physiology and can result in neuropsychiatric diseases. Recent molecular research has linked various epigenetic processes, such as DNA methylation, histone modifications, and noncoding RNAs, to the dysregulation of genes in the impacted brain circuits responsible for the pathophysiology of chronic stress. Numerous disorders, including neurodegenerative diseases (NDDs) including Alzheimer's, amyotrophic lateral sclerosis, Friedreich's ataxia, Huntington's disease, multiple sclerosis, and Parkinson's disease, have been linked to oxidative stress as a possible cause.},
}

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

@article {pmid40222103,
year = {2025},
author = {Lum, JS and Brown, ML and Farrawell, NE and Bartlett, R and Chisholm, CG and Gorman, J and Dosseto, A and Dux, F and McInnes, LE and Ecroyd, H and McAlary, L and Crouch, PJ and Donnelly, PS and Yerbury, JJ},
title = {A polytherapy approach demonstrates therapeutic efficacy for the treatment of SOD1 associated amyotrophic lateral sclerosis.},
journal = {EBioMedicine},
volume = {115},
number = {},
pages = {105692},
doi = {10.1016/j.ebiom.2025.105692},
pmid = {40222103},
issn = {2352-3964},
abstract = {BACKGROUND: SOD1 mutations are a significant contributor of familial amyotrophic lateral sclerosis (ALS) cases. SOD1 mutations increase the propensity for the protein to misfold and aggregate into insoluble proteinaceous deposits within motor neurons and neighbouring cells. The small molecule, CuATSM, has repeatedly shown in mouse models to be a promising therapeutic treatment for SOD1-associated ALS and is currently in Phase II/III clinical trials for the treatment of ALS. We have previously shown CuATSM stabilises various ALS-associated variants of the SOD1 protein, reducing misfolding and toxicity. Two additional FDA-approved small molecules, ebselen and telbivudine, have also been identified to reduce mutant SOD1 toxicity, providing additional potential therapeutic candidates that could be used in combination with CuATSM. Here, we aimed to investigate if CuATSM, ebselen and telbivudine (CET) polytherapy could improve on the therapeutic efficacy of CuATSM monotherapy for the treatment of SOD1-associated ALS.

METHODS: We utilised a 3D checkerboard approach to investigate whether a matrix of different concentrations CuATSM, ebselen and telbivudine could provide therapeutic improvements on cell survival, SOD1 folding and aggregation in SOD1[G93A]-transfected NSC-34 cells, compared to CuATSM alone. To progress the preclinical development of CET polytherapy, we evaluated the bioavailability and safety of in vivo polytherapy administration. Furthermore, we assessed and compared the effects of CET- and CuATSM-treatment on disease onset, motor function, survival and neuropathological features in SOD1[G93A] mice.

FINDINGS: CET polytherapy reduced inclusion formation and increased cell survival of NSC-34 cells overexpressing SOD1[G93A] compared to higher concentrations of CuATSM monotherapy. In addition, CET administration was bioavailable and tolerable in mice. CET treatment in SOD1[G93A] mice delayed disease onset, reduced motor impairments, and increased survival compared to vehicle- and CuATSM-treated mice. In line with these findings, biochemical analysis of lumbar spinal cords showed CET administration improved SOD1 folding, decreased misfolded SOD1 accumulation, and reduced motor neuron loss.

INTERPRETATION: These findings support CET polytherapy as an advantageous alternative compared to CuATSM monotherapy and highlight the potential of utilising small molecules targeting SOD1 as a polytherapy avenue for the treatment of SOD1-associated ALS.

FUNDING: This work was supported by a FightMND Drug Development Grant, an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (No. 1194872) and a Motor Neuron Disease Research Institute of Australia Bill Gole Postdoctoral Fellowship.},
}

@article {pmid40222004,
year = {2025},
author = {Oliveri, F and Bicaj, M and Cillerai, M and Cabona, C and Gemelli, C and Uccelli, A and Schenone, A and Ferraro, PM},
title = {Prevalence of cognitive impairment in motor neuron diseases: alternative norming methods lead to considerably diverse estimates.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/21678421.2025.2488294},
pmid = {40222004},
issn = {2167-9223},
abstract = {Objectives: Cognitive impairment (CI) is frequently observed in motor neuron diseases (MNDs), and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) represents the most widely used measure to evaluate it. For the Italian ECAS, two norming approaches are currently available: the "regression-based" (R) and the "2 standard deviation-based" (2SD). In this study, we therefore aimed at comparing those two methods for the detection of CI in MNDs. Methods: Raw ECAS scores from 160 MND patients were corrected using both the R and the 2SD methods. According to Strong's criteria, patients were then categorized as either cognitively normal (CN), with CI (ALSci), with behavioral impairment (ALSbi), or both (ALScbi). Results: Using the R approach, the frequency of below-cutoff performances was 3.12% for the ECAS total, 4.37% for the ALS specific, and 3.75% for the ALS nonspecific score. Using the 2SD method, the prevalence increased to 25.62% for the ECAS total, 21.25% for the ALS specific, and 23.12% for the ALS nonspecific score. The same increase was observed across all single tasks except for the digit span backward. The R-based frequency of Strong's diagnoses was 7.50% for ALSci, 15.62% for ALSbi, and 3.14% for ALScbi, which became 24.38% for ALSci, 8.75% for ALSbi and 10% for ALScbi with the 2SD method. Conclusions: The norming approach has a significant impact on the estimated prevalence of CI in MNDs, with the R method representing the most conservative one. These findings highlight the need for harmonized protocols in future studies evaluating CI in MNDs.},
}

@article {pmid40220918,
year = {2025},
author = {Key, J and Almaguer-Mederos, LE and Kandi, AR and Sen, NE and Gispert, S and Köpf, G and Meierhofer, D and Auburger, G},
title = {ATXN2L primarily interacts with NUFIP2, the absence of ATXN2L results in NUFIP2 depletion, and the ATXN2-polyQ expansion triggers NUFIP2 accumulation.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {106903},
doi = {10.1016/j.nbd.2025.106903},
pmid = {40220918},
issn = {1095-953X},
abstract = {The cytoplasmic Ataxin-2 (ATXN2) protein associates with TDP-43 in stress granules (SG) where RNA quality control occurs. Mutations in this pathway underlie Spinocerebellar Ataxia type 2 (SCA2) and Amyotrophic Lateral Sclerosis. In contrast, Ataxin-2-like (ATXN2L) is predominantly perinuclear, more abundant, and essential for embryonic life. Its sequestration into ATXN2 aggregates may contribute to disease. In this study, we utilized two approaches to clarify the roles of ATXN2L. First, we identified interactors through co-immunoprecipitation in both wild-type and ATXN2L-null murine embryonic fibroblasts. Second, we assessed the proteome profile effects using mass spectrometry in these cells. Additionally, we examined the accumulation of ATXN2L interactors in the SCA2 mouse model, Atxn2-CAG100-KnockIn (KIN). We observed that RNA-binding proteins, including PABPN1, NUFIP2, MCRIP2, RBMS1, LARP1, PTBP1, FMR1, RPS20, FUBP3, MBNL2, ZMAT3, SFPQ, CSDE1, HNRNPK, and HNRNPDL, exhibit a stronger association with ATXN2L compared to established interactors like ATXN2, PABPC1, LSM12, and G3BP2. Additionally, ATXN2L interacted with components of the actin complex, such as SYNE2, LMOD1, ACTA2, FYB, and GOLGA3. We noted that oxidative stress increased HNRNPK but decreased SYNE2 association, which likely reflects the relocalization of SG. Proteome profiling revealed that NUFIP2 and SYNE2 are depleted in ATXN2L-null fibroblasts. Furthermore, NUFIP2 homodimers and SYNE1 accumulate during the ATXN2 aggregation process in KIN 14-month-old spinal cord tissues. The functions of ATXN2L and its interactors are therefore critical in RNA granule trafficking and surveillance, particularly for the maintenance of differentiated neurons.},
}

@article {pmid40220686,
year = {2025},
author = {Coloma, L and Aramendia, J and Amigo, JM and Población, I and Alberquilla, F and Gorla, G and Huidobro, J and Torre-Fdez, I and Arana, G and Madariaga, JM},
title = {Analysis and interpretation of organic compounds in Martian meteorites with Raman imaging and chemometrics.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {338},
number = {},
pages = {126194},
doi = {10.1016/j.saa.2025.126194},
pmid = {40220686},
issn = {1873-3557},
abstract = {One of the focuses of the research being developed on Mars (and consequently in samples from Mars) is the detection and study of organic compounds. Perseverance rover, currently analysing the Martian surface, is equipped with top-level instrumentation to detect mostly organic molecules. One of the techniques being used is Raman spectroscopy, due to its capability to analyse both inorganic and organic compounds simultaneously and its non-destructive and non-invasive properties. Unfortunately, it becomes cumbersome to determine the belonging of specific Raman bands in complex mixtures composed of an undetermined number of organic and inorganic molecules. Therefore, the study of this mixed information must be carried out with dedicated Chemometrics methods in order to understand the number of compounds present in a mixture (using Principal Component Analysis - PCA) and to obtain the pure spectra and the relative intensity of each compound (using spectral unmixing methods like Multivariate Curve Resolution - MCR). This manuscript presents an analysis of specific areas from the NWA 6148 Martian Nakhlite using Raman imaging, coupled with principal component analysis (PCA) and multivariate curve resolution (MCR), to determine the spatial distribution and spectral signatures of all organic and inorganic molecules present in these areas. The proposed methodology could be applied to the laboratory study of the future Mars-returned samples and other extraterrestrial samples returned to Earth.},
}

@article {pmid40219902,
year = {2025},
author = {Lapp, HS and Günther, R},
title = {SOD1-ALS mimicking an inflammatory neuropathy: a case report.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/21678421.2025.2488296},
pmid = {40219902},
issn = {2167-9223},
abstract = {We present the case of a 36-year-old patient with a rapidly progressing SOD1-ALS, who was initially diagnosed as inflammatory acute motor axonal neuropathy due to contrast-enhancement of the lumbar spinal cord and a pure secondary motor neuron phenotype. Since the initiation of tofersen, disease progression and neurofilament levels impressively declined.},
}

@article {pmid40218232,
year = {2025},
author = {Iglesias, M and Cascón, JA and Maimó, A and Albaladejo, A and Andreo, F and Fernández, AS and Palazón, MM and González-Posada, IM and García, RG and Cordovilla, R},
title = {Evaluation of Diaphragmatic Ultrasound in Respiratory Functional Assessment in Patients with ALS.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/diagnostics15070884},
pmid = {40218232},
issn = {2075-4418},
support = {becaPII2019//SOCIEDAD ESPAÑOLA DE NEUMOLOGÍA Y CIRUGÍA TORÁCICA (SEPAR)/ ; },
abstract = {Background: Diaphragmatic ultrasound emerges as a valuable non-invasive method for assessing diaphragm functionality in patients with amyotrophic lateral sclerosis (ALS). This study aimed to evaluate diaphragmatic ultrasound parameters in ALS, compare them with respiratory function tests, and determine whether they are associated with the need for non-invasive ventilation (NIV). Methods: This was a prospective, descriptive, and multicenter study across five centers, enrolling patients with recent diagnoses of ALS. At three-monthly visits, participants underwent both diaphragmatic ultrasound and pulmonary function testing. The following variables were analyzed: withdrawal from this study due to NIV or death, excursion, velocity, thickness, thickening fraction, and spirometric and respiratory muscle function values. Results: A total of 41 patients were included. A total of 24 (61.5%) patients left this study before the final year: 17 due to initiation of NIV, 4 due to clinical deterioration without NIV, and 3 due to death. Statistically significant moderate correlations were observed between diaphragmatic excursion and velocity and FVC and supine FVC (p < 0.001) and with MIP and the SNIP test (p < 0.05). No correlation was observed with thickening fraction. Additionally, lower baseline values in excursion were significantly associated with study withdrawal, along with reduced lung function (FVC, supine FVC, and MEP (p < 0.001). Conclusions: assessing diaphragmatic excursion by ultrasonography may serve as a useful tool for monitoring patients with ALS.},
}

@article {pmid40217081,
year = {2025},
author = {Baek, SH and Tae, WS and Auer, D and Kim, BJ},
title = {Brain diffusion tensor imaging changes linked to the split hand phenomenon in amyotrophic lateral sclerosis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {12450},
pmid = {40217081},
issn = {2045-2322},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology ; Male ; *Diffusion Tensor Imaging/methods ; Female ; Aged ; Middle Aged ; *Brain/diagnostic imaging/pathology/physiopathology ; Pyramidal Tracts/diagnostic imaging/pathology/physiopathology ; Anisotropy ; White Matter/diagnostic imaging/pathology ; },
abstract = {The split-hand phenomenon is an early and specific feature of amyotrophic lateral sclerosis (ALS). This study aimed to investigate whether the split-hand phenomenon in ALS is associated with the white matter degeneration of the brain. Patients diagnosed with clinically definite or probable ALS were prospectively recruited and underwent both nerve conduction studies to assess the split-hand index (SHI) and brain diffusion tensor imaging (DTI). Demographic, clinical, and electrophysiological data were all collected. A total of 35 patients with ALS (18 male; median age, 66.0 years) were enrolled in this study. The axial diffusivity (AD) and mode of anisotropy (MO) values of DTI in the corticospinal tract (CST) positively correlated with the SHI. However, there were no significant correlations between the SHI and the fraction anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) scalars. In addition, patients having ALS with bilateral split-hand phenomenon showed reduced AD values in the left CST and reduced MO values in the bilateral CST compared with those without the split-hand phenomenon. However, there were no significant differences in FA, MD, and RD scalars. Our findings suggest that the split-hand phenomenon is associated with degenerative brain changes, particularly in the CST.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology
Male
*Diffusion Tensor Imaging/methods
Female
Aged
Middle Aged
*Brain/diagnostic imaging/pathology/physiopathology
Pyramidal Tracts/diagnostic imaging/pathology/physiopathology
Anisotropy
White Matter/diagnostic imaging/pathology

@article {pmid40216746,
year = {2025},
author = {Rezaei, A and Kocsis-Jutka, V and Gunes, ZI and Zeng, Q and Kislinger, G and Bauernschmitt, F and Isilgan, HB and Parisi, LR and Kaya, T and Franzenburg, S and Koppenbrink, J and Knogler, J and Arzberger, T and Farny, D and Nuscher, B and Katona, E and Dhingra, A and Yang, C and Gouna, G and LaClair, KD and Janjic, A and Enard, W and Zhou, Q and Hagan, N and Ofengeim, D and Beltrán, E and Gokce, O and Simons, M and Liebscher, S and Edbauer, D},
title = {Correction of dysregulated lipid metabolism normalizes gene expression in oligodendrocytes and prolongs lifespan in female poly-GA C9orf72 mice.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {3442},
pmid = {40216746},
issn = {2041-1723},
support = {390857198//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 407495230//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 423957469//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 390857198//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 390857198//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 101057649//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 101117710//EC | EU Framework Programme for Research and Innovation H2020 | H2020 European Institute of Innovation and Technology (H2020 The European Institute of Innovation and Technology)/ ; },
mesh = {Animals ; Female ; Mice ; *Oligodendroglia/metabolism/drug effects ; *Lipid Metabolism/drug effects/genetics ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/drug therapy/pathology ; *C9orf72 Protein/genetics/metabolism ; Disease Models, Animal ; Male ; Cholesterol/metabolism ; Humans ; *2-Hydroxypropyl-beta-cyclodextrin/pharmacology ; Mice, Transgenic ; Myelin Sheath/metabolism ; Spinal Cord/metabolism/pathology ; Longevity/drug effects/genetics ; },
abstract = {Clinical and genetic research links altered cholesterol metabolism with ALS development and progression, yet pinpointing specific pathomechanisms remain challenging. We investigated how cholesterol dysmetabolism interacts with protein aggregation, demyelination, and neuronal loss in ALS. Bulk RNAseq transcriptomics showed decreased cholesterol biosynthesis and increased cholesterol export in ALS mouse models (GA-Nes, GA-Camk2a GA-CFP, rNLS8) and patient samples (spinal cord), suggesting an adaptive response to cholesterol overload. Consequently, we assessed the efficacy of the cholesterol-binding drug 2-hydroxypropyl-β-cyclodextrin (CD) in a fast-progressing C9orf72 ALS mouse model with extensive poly-GA expression and myelination deficits. CD treatment normalized cholesteryl ester levels, lowered neurofilament light chain levels, and prolonged lifespan in female but not male GA-Nes mice, without impacting poly-GA aggregates. Single nucleus transcriptomics indicated that CD primarily affected oligodendrocytes, significantly restored myelin gene expression, increased density of myelinated axons, inhibited the disease-associated oligodendrocyte response, and downregulated the lipid-associated genes Plin4 and ApoD. These results suggest that reducing excess free cholesterol in the CNS could be a viable ALS treatment strategy.},
}

Animals
Female
Mice
*Oligodendroglia/metabolism/drug effects
*Lipid Metabolism/drug effects/genetics
*Amyotrophic Lateral Sclerosis/genetics/metabolism/drug therapy/pathology
*C9orf72 Protein/genetics/metabolism
Disease Models, Animal
Male
Cholesterol/metabolism
Humans
*2-Hydroxypropyl-beta-cyclodextrin/pharmacology
Mice, Transgenic
Myelin Sheath/metabolism
Spinal Cord/metabolism/pathology
Longevity/drug effects/genetics

@article {pmid40216201,
year = {2025},
author = {Cagalinec, M and Adnan, M and Borecka, S and Bultynck, G and Choubey, V and Yanovsky-Dagan, S and Ezer, S and Gasperikova, D and Harel, T and Jurkovicova, D and Kaasik, A and Liévens, JC and Maurice, T and Peviani, M and Richard, EM and Skoda, J and Skopkova, M and Tarot, P and Van Gorp, R and Zvejniece, L and Delprat, B},
title = {Improving mitochondria-associated endoplasmic reticulum membranes integrity as converging therapeutic strategy for rare neurodegenerative diseases and cancer.},
journal = {Biochimica et biophysica acta. Molecular cell research},
volume = {},
number = {},
pages = {119954},
doi = {10.1016/j.bbamcr.2025.119954},
pmid = {40216201},
issn = {1879-2596},
abstract = {Membrane contact sites harbor a distinct set of proteins with varying biological functions, thereby emerging as hubs for localized signaling nanodomains underlying adequate cell function. Here, we will focus on mitochondria-associated endoplasmic reticulum membranes (MAMs), which serve as hotspots for Ca[2+] signaling, redox regulation, lipid exchange, mitochondrial quality and unfolded protein response pathway. A network of MAM-resident proteins contributes to the structural integrity and adequate function of MAMs. Beyond endoplasmic reticulum (ER)-mitochondrial tethering proteins, MAMs contain several multi-protein complexes that mediate the transfer of or are influenced by Ca[2+], reactive oxygen species and lipids. Particularly, IP3 receptors, intracellular Ca[2+]-release channels, and Sigma-1 receptors (S1Rs), ligand-operated chaperones, serve as important platforms that recruit different accessory proteins and intersect with these local signaling processes. Furthermore, many of these proteins are directly implicated in pathophysiological conditions, where their dysregulation or mutation is not only causing diseases such as cancer and neurodegeneration, but also rare genetic diseases, for example familial Parkinson's disease (PINK1, Parkin, DJ-1), familial Amyotrophic lateral sclerosis (TDP43), Wolfram syndrome1/2 (WFS1 and CISD2), Harel-Yoon syndrome (ATAD3A). In this review, we will discuss the current state-of-the-art regarding the molecular components, protein platforms and signaling networks underlying MAM integrity and function in cell function and how their dysregulation impacts MAMs, thereby driving pathogenesis and/or impacting disease burden. We will highlight how these insights can generate novel, potentially therapeutically relevant, strategies to tackle disease outcomes by improving the integrity of MAMs and the signaling processes occurring at these membrane contact sites.},
}

@article {pmid40215589,
year = {2025},
author = {Yaguchi, H and Miyagawa, S and Nakada, R and Yamamoto, S and Sakuta, K},
title = {Speech-swallow dissociation in velopharyngeal closure for differentiating amyotrophic lateral sclerosis and myasthenia gravis.},
journal = {Auris, nasus, larynx},
volume = {52},
number = {3},
pages = {239-242},
doi = {10.1016/j.anl.2025.03.003},
pmid = {40215589},
issn = {1879-1476},
abstract = {OBJECTIVE: Speech-swallow dissociation (SSD) in velopharyngeal closure on laryngoscopy is a sign of pseudobulbar palsy. We hypothesized that this finding could differentiate amyotrophic lateral sclerosis (ALS) from myasthenia gravis (MG). This study aimed to identify laryngoscopic findings useful in differentiating these two diseases.

METHODS: ALS and MG patients with bulbar symptoms who underwent fiberoptic laryngoscopy in our hospital were retrospectively examined. The following laryngoscopic items were evaluated: velopharyngeal incompetence (VPI) in phonation and swallowing, pharyngeal constriction, vocal cord movement, and salivary status.

RESULTS: One hundred seven patients (70 with ALS and 37 with MG) were included for analysis. The prevalence of VPI in phonation was significantly higher in the ALS group (40 % vs. 19 %; P = 0.027). The prevalence of SSD in velopharyngeal closure was also significantly higher in the ALS group (33 % vs. 3 %; P < 0.001). The other laryngoscopic findings did not differ between the groups. Multivariate logistic regression showed that SSD in velopharyngeal closure was independently associated with ALS (odds ratio, 26.64; 95 % confidence interval, 2.24-317.58; P = 0.009).

CONCLUSION: SSD in velopharyngeal closure is useful for differentiating ALS from MG.},
}

@article {pmid40214652,
year = {2025},
author = {Yu, G and Liu, X and Huang, W and Wang, S and Zhan, J and Ma, L and Li, H and Lin, X and Liu, T and Amine, K and Li, H},
title = {Ferromagnetic Atomic d-p Orbital Hybridization for Promoting Al-S Batteries.},
journal = {Advanced materials (Deerfield Beach, Fla.)},
volume = {},
number = {},
pages = {e2418784},
doi = {10.1002/adma.202418784},
pmid = {40214652},
issn = {1521-4095},
support = {tsqn202211118//Taishan Scholar Program of Shandong Province/ ; ZR2023YQ008//Excellent Youth Science Fund Project of Shandong China/ ; 2021KJ020//Outstanding Youth Innovation Team of Universities in Shandong Province/ ; 51804173//National Natural Science Foundation (NSFC) of China/ ; DE-SC0012704//Brookhaven National Laboratory under contract/ ; },
abstract = {Rechargeable aluminum-sulfur batteries (Al-S) are emerging as a promising alternative energy storage system beyond lithium-ion batteries due to their high energy density, abundant material resources, and economic efficiency. However, their practical application remains challenged by sluggish conversion kinetics, polysulfide shuttling, and low sulfur cathode utilization. While extensive studies have focused on enhancing polysulfide adsorption through catalytic strategies, the roles of electronic structure in dictating catalytic performance remain underexplored. Here, this work unveils the critical effect of unpaired electronic structure on the catalytic performance of single atom ferromagnetic transition metals through a systematic evaluation of three typical atomically dispersed ferromagnetic single atoms-Fe, Co, and Ni-supported on porous carbon (denoted as PC-SAFAs). Comprehensive characterizations and density functional theory (DFT) calculations reveal that the PC-SAFe catalysts, exhibiting the highest spin polarization arising from unpaired electrons, demonstrate the strongest interactions with polysulfide, thereby facilitating rapid and reversible polysulfide conversion reactions. Consequently, Al-S batteries incorporating the optimized PC-SAFe cathode achieve an impressive specific capacity of 508.8 mAh g[-1] at 1.0 A g[-1] after 500 cycles, along with much improved rate capability. This work provides a deeper understanding of the role of electronic structure in catalytic chemistry, and offers new insights for developing high-performance Al-S batteries.},
}

@article {pmid40214138,
year = {2025},
author = {Reus, LM and Willemse, SW and de Boer, SCM and De Houwer, J and Hartog, WL and Mol, MO and van Rooij, JGJ and Tesi, N and Donker Kaat, L and Hulsman, M and Vijverberg, EGB and Holstege, H and van Rheenen, W and Veldink, JH and van den Berg, LH and van Swieten, JC and Seelaar, H and van der Lee, SJ and van Es, MA and Pijnenburg, YAL},
title = {UNC13A Polymorphism Influences Survival in Patients with Frontotemporal Dementia.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.27245},
pmid = {40214138},
issn = {1531-8249},
abstract = {UNC13A (rs12608932-CC) is associated with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and shortens survival in ALS. We aim to describe the association for UNC13A and survival in FTD. We included 626 patients with FTD from Dutch memory clinics, including a subcohort of 150 patients with TDP-43 pathology. Survival analyses were performed using Cox proportional hazard models in a recessive manner. Homozygosity for rs12608932-C in UNC13A was associated with a shorter survival compared with other genotypes (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.02-1.60, p = 0.033), which has implications for patient counselling and trial design. ANN NEUROL 2025.},
}

@article {pmid40213728,
year = {2025},
author = {Grigore, A and Goebel, LJ},
title = {Frontotemporal Dementia and Amyotrophic Lateral Sclerosis: A Case Report and Clinical Insights.},
journal = {Cureus},
volume = {17},
number = {3},
pages = {e80329},
pmid = {40213728},
issn = {2168-8184},
abstract = {Primary care providers are often the first contact for patients with neurodegenerative illnesses, however, they may not be aware of the relationship of certain diseases that may have an impact on their patients' longevity. This case report reminds clinicians of the association between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Physicians should be aware of the association, because FTD commonly occurs first and may prepare clinicians to be alert to the signs of ALS in these patients, leading to earlier detection of ALS and the prescription of disease-modifying medication that may extend the lifespan of people with these diseases. We describe the case of a 61-year-old female patient initially presenting with cognitive decline most likely due to FTD who subsequently developed ALS.},
}

@article {pmid40213632,
year = {2025},
author = {Dezawa, M},
title = {Macrophage- and pluripotent-like reparative Muse cells are unique endogenous stem cells distinct from other somatic stem cells.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {13},
number = {},
pages = {1553382},
pmid = {40213632},
issn = {2296-4185},
abstract = {Muse cells are endogenous reparative stem cells with dual characteristics: pluripotent-like and macrophage-like. They can be identified by the pluripotent surface marker stage-specific embryonic antigen-3-positive (SSEA-3 (+)) cells in the bone marrow, peripheral blood, and various organs, including the umbilical cord and amnion. Muse cells can differentiate into ectodermal, endodermal, and mesodermal lineage cells, self-renew, and selectively migrate to damaged sites by sensing one of the universal tissue damage signals, sphingosine-1-phosphate (S1P). At these sites, they phagocytose damaged/apoptotic cells and differentiate into the same cell type as the phagocytosed cells. In this manner, Muse cells replace damaged/apoptotic cells with healthy, functioning cells, thereby repairing tissues. Due to their specific immunosuppressive and immunotolerant mechanism, clinical trials have been conducted for acute myocardial infarction (AMI), subacute ischemic stroke, epidermolysis bullosa, amyotrophic lateral sclerosis (ALS), cervical spinal cord injury, neonatal hypoxic-ischemic encephalopathy (HIE), and COVID-19 acute respiratory distress syndrome. These trials involved the intravenous injection of ∼1.5 × 10[7] donor Muse cells without human leukocyte antigen (HLA) matching or immunosuppressant treatment, and they demonstrated safety and therapeutic efficacy. Thus, donor Muse cell treatment does not require gene manipulation, differentiation induction, or surgical intervention. These unique characteristics distinguish Muse cells from other somatic stem cells, such as mesenchymal stem cells, VSEL stem cells, and marrow-isolated adult multi-lineage inducible (MIAMI) cells.},
}

@article {pmid40212206,
year = {2025},
author = {Basnet, P and Singh, PR and Pudasaini, KR and Shrestha, S and Kc, A},
title = {A rare case of symmetric quadriplegia in a patient with Japanese encephalitis: a case report.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {4},
pages = {2430-2433},
pmid = {40212206},
issn = {2049-0801},
abstract = {INTRODUCTION AND IMPORTANCE: Acute flaccid paralysis is a rare neurological complication of Japanese encephalitis (JE) infection, which may involve one or multiple limbs. Symmetric involvement of upper and lower limbs such as in this case is rarely reported.

PRESENTATION OF CASE: We present a case of a 30-year-old male from Terai region of Nepal who presented with fever, altered level of consciousness, and symmetrical quadriplegia. Based on these clinical findings, cerebrospinal fluid (CSF) analysis was done which came back negative. And based on results, polymerase chain reaction for herpes simplex virus types I and II was done which came out negative. Other neurological conditions such as amyotrophic lateral sclerosis and spinal dystrophy were ruled out because of the presence of fever and altered mental status. He was eventually diagnosed with JE based on his CSF analysis and positive result for JE serology/IgM Antibody Capture Enzyme-Linked Immunosorbent Assay test.

CLINICAL DISCUSSION: The patient presented with fever, altered mental status, and symmetrical flaccid paralysis of the bilateral upper and lower limb. Symmetrical involvement of the upper and the lower limbs is unusual in most cases of JE.

CONCLUSION: This case highlights the importance of awareness on the part of the clinician about the possibilities of atypical presentation in JE. It also emphasizes that Japanese encephalitis should be a part of the differential in patients with atypical neurological presentation in endemic areas.},
}

@article {pmid40212027,
year = {2025},
author = {Menezes, AT and Nagasse, HY and Lopes, HRM and Coltri, PP},
title = {Design of a GFP reporter for splicing analysis in mammalian cells.},
journal = {Biotechnology reports (Amsterdam, Netherlands)},
volume = {46},
number = {},
pages = {e00887},
pmid = {40212027},
issn = {2215-017X},
abstract = {Eukaryotic genes are formed by exons and introns. Pre-mRNA splicing promotes exon ligation and intron removal and is performed by a specialized macromolecular machinery named spliceosome, composed of five small ribonucleoprotein particles (snRNPs) and more than one hundred proteins. The activity of this complex is highly accurate due to the coordinated activity of its components. Altered splicing has been related to the development of several diseases, including neurodegenerative disorders, such as amyotrophic lateral sclerosis, and different types of cancer. Detailed understanding of splicing regulation in eukaryotic cells can be achieved using splicing reporter systems. We designed a reporter plasmid suitable for splicing analysis in cultured mammalian cells. Our reporter is based on GFP expression, and the splicing outcome can be easily visualized by fluorescence microscopy. We quantified splicing activity in two human cell lines, HEK-293T and MDA-MB-231, confirming its suitability for use in live cells in culture.},
}