@article {pmid41617608,
year = {2026},
author = {Tankéré, P and Bernard, E and Herquelot, E and Denis, H and Sfeir, L and Saint-Raymond, C and Mallaret, M and Lavergne, F and Baillieul, S and Peter-Derex, L and Tamisier, R and Pépin, JL},
title = {Health trajectories of patients with amyotrophic lateral sclerosis before and after initiation of non-invasive ventilation: a French nationwide database analysis.},
journal = {Thorax},
volume = {},
number = {},
pages = {},
doi = {10.1136/thorax-2025-223974},
pmid = {41617608},
issn = {1468-3296},
abstract = {BACKGROUND: Management of amyotrophic lateral sclerosis (ALS) is complicated by heterogeneous presentation and unpredictable disease course. This study described disease trajectories before and after initiation of non-invasive ventilation (NIV) therapy in individuals with ALS, examined the relationship between NIV initiation timing and survival and analysed health trajectory clusters.

METHODS: Data were extracted from the French national health insurance reimbursement system database for individuals with ≥1 reimbursement for NIV from January 2015 to December 2019, and ≥1 ALS disease code. Health trajectory clusters were determined using time sequence analysis through K-clustering.

RESULTS: We analysed data from 3443 individuals with ALS (58% male, median age 67 years). The median (IQR) time from ALS diagnosis to NIV initiation was 10.8 (4.5-22.2) months and death occurred 21.5 (12.8-33.9) months after diagnosis. Tracheostomy/gastrostomy was performed in 3.9%/33.4% of patients, respectively. Unsupervised machine learning clustering identified four distinct patient groups. NIV initiation was late in two Clusters (A and B); these individuals were younger, had fewer comorbidities and more physiotherapy sessions before/after NIV. Survival after NIV initiation was longer in Clusters B and C; these individuals had lower rates of depression/anxiety, more prescription of mechanical in/exsufflation therapy and fewer home and emergency hospitalisations. Cluster B was unique, showing late NIV initiation and long post-NIV survival. This cluster was more likely to have spinal onset, a higher rate of obstructive sleep apnoea and fewer comorbidities.

CONCLUSIONS: There was marked heterogeneity between patients with ALS and their care trajectories. Our data do not support a universal benefit for early initiation of NIV therapy.},
}

@article {pmid41616251,
year = {2026},
author = {Sang, Y and Ren, J and Aballay, A},
title = {A gut-activated NHR-86-CYP pathway mediates the neuroprotective effects of Enterococcus faecium probiotics in a nematode model of amyotrophic lateral sclerosis.},
journal = {PLoS biology},
volume = {24},
number = {1},
pages = {e3003627},
doi = {10.1371/journal.pbio.3003627},
pmid = {41616251},
issn = {1545-7885},
abstract = {Neurodegenerative diseases are often associated with oxidative stress, and while probiotics may influence neuronal health, the underlying mechanisms remain poorly understood. Using the sod-1 A4VM amyotrophic lateral sclerosis (ALS) model in Caenorhabditis elegans, we investigated the protective effects of the probiotic Enterococcus faecium against oxidative stress-induced neurodegeneration. Animals fed E. faecium showed reduced motor neuron degeneration under oxidative stress compared to those maintained on a standard Escherichia coli diet. Transcriptome analysis revealed a significant enrichment of oxidoreductase genes, including cytochrome P450 (cyp) genes. RNAi-mediated knockdown of cyp genes impaired E. faecium-mediated neuroprotection, and this loss correlated with increased reactive oxygen species (ROS) levels. We identified the conserved nuclear hormone receptor NHR-86 as a key regulator of cyp gene expression and neuroprotection. Loss of nhr-86 abolished the probiotic's protective benefits, while transgenic expression of nhr-86 restored cyp induction and neuronal resilience. Importantly, intestinal expression of NHR-86 was sufficient to restore CYP induction and neuronal resilience, whereas neuronal knockdown had no effect, indicating that gut NHR-86 activity is essential for this protective pathway. These findings reveal a previously uncharacterized NHR-CYP regulatory axis activated by an intestinal probiotic, highlighting a mechanistic link between microbial signals and host neuroprotection.},
}

@article {pmid41616079,
year = {2026},
author = {Steenkjaer, CH and Storgaard, JH and Levison, L and Blicher, JU},
title = {A national survey of pseudobulbar affect and symptomatic treatment in Amyotrophic Lateral Sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2026.2620448},
pmid = {41616079},
issn = {2167-9223},
abstract = {OBJECTIVE: We aimed to determine diagnostic prevalence and symptom burden of pseudobulbar affect (PBA) in patients with Amyotrophic Lateral Sclerosis (ALS) in Denmark and differences in ongoing symptomatic treatment.

METHODS: In this national cross-sectional survey study, participants with ALS completed an online survey regarding PBA and PBA symptoms, which were quantified through the Center for Neurologic Study Lability Scale (CNS-LS). A CNS-LS score ≥ 13 served as a threshold indicative of PBA.

RESULTS: 157 participants with ALS were recruited. 12.1% were diagnosed with PBA and were more likely to receive antidepressant medication compared to those not diagnosed with PBA (47.4% compared to 15.2%, p = 0.002). 30.6% scored ≥13 in the CNS-LS; however, the proportion of participants treated with antidepressants was similar compared to those scoring below the ≥13 threshold (25% compared to 16.5%, p = 0.27). Of those not diagnosed with PBA, 23.2% scored ≥13 in the CNS-LS. This PBA symptomatic, but undiagnosed group was less likely to receive symptomatic treatment compared to patients with diagnosed PBA (12.5% compared to 47.4%, p = 0.009). No differences were seen in CNS-LS score between these groups.

CONCLUSIONS: The proportion of diagnosed PBA among the study population was low compared to previous studies; however, the proportion of patients with symptoms of possible PBA was markedly higher. Patients with known PBA were more likely to receive recommended symptomatic treatment compared to patients not diagnosed with PBA, despite symptoms indicative of PBA. These findings highlight the potential underrecognition of PBA in ALS and concurrent absence of symptomatic treatment.},
}

@article {pmid41615807,
year = {2026},
author = {Azizzadeh, M and Pirker-Kees, A and Wouters, EFM and Janssen, DJA and Spaetgens, B and Breyer-Kohansal, R and Breyer, MK},
title = {Association of allostatic load with frailty trajectories and the mediating role of depressive symptoms.},
journal = {The Journal of frailty & aging},
volume = {15},
number = {2},
pages = {100132},
doi = {10.1016/j.tjfa.2026.100132},
pmid = {41615807},
issn = {2260-1341},
abstract = {BACKGROUND: Frailty is a dynamic, age-related condition marked by progressive loss of resilience. Its risk factors include socioeconomic status and physiological stress burden, such as allostatic load score (ALS), remain unclear. This study aims to examine the role of depression in the association between ALS and frailty trajectories.

METHODS: We analyzed data from 5885 LEAD cohort participants aged 25-82 years at baseline and from 3564 participants with follow-up data. Frailty status (robust, pre-frail, frail) was defined using the Fried phenotype, and transitions between visits were assessed. ALS was calculated from 14 parameters spanning cardiovascular, metabolic, and body composition measures. Associations of ALS with frailty status at baseline and with frailty transitions at follow-up were examined, and depressive symptoms were tested as a mediator.

RESULTS: At baseline, 62.3% of participants were robust, 36.2% pre-frail, and 1.5% frail. Between visits, 16.3% transitioned to a worse frailty stage, while 17.7% improved. Higher ALS was linked to increased odds of being pre-frail/frail at baseline (OR 1.11; 95% CI: 1.08-1.15), and to a higher risk of transitioning from robust to pre-frail/frail (RRR 1.06; 95% CI: 1.02-1.09). Depressive symptoms mediated 35% (95% CI: 25-47%) of the cross-sectional and 17% (95% CI: 6.6-43%) of the longitudinal association between ALS and frailty.

CONCLUSIONS: Socioeconomic factors influenced frailty onset but not its progression, whereas depressive symptoms mediated approximately 17% of the effect of ALS on frailty development over time. These findings highlight the importance of exploring the effect of interventions for depression on frailty progression.},
}

@article {pmid41614607,
year = {2026},
author = {Combe, P and Subecz, C and Le Goff, G and Plamont, MA and Bohl, D and Gueroui, Z},
title = {Concentration-dependent cytoplasmic phase separation of TDP-43 drives aggregation and proteinopathy.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70429},
pmid = {41614607},
issn = {1742-4658},
support = {MND202003011470//Fondation pour la Recherche Médicale/ ; },
abstract = {TDP-43 mislocalization and aggregation are common features of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the mechanisms underlying the transition of nuclear TDP-43 to cytoplasmic aggregates, and their contribution to disease pathogenesis, remain poorly understood. To address this gap, we present a methodology to chemically control the assembly and disassembly of cytoplasmic TDP-43 condensates. By fusing TDP-43 to a phase separation-prone protein scaffold, we can induce the formation of cytoplasmic TDP-43 condensates or, conversely, promote nuclear localization upon addition of a disassembly molecule. TDP-43 accumulates into various assemblies, ranging from submicrometric puncta to larger aggregate-like structures that display hallmarks of proteinopathy in a concentration-dependent manner. Furthermore, oxidative stress drives the maturation of TDP-43 assemblies from puncta into aggregates through interactions with stress granule components. Finally, we show that cytoplasmic TDP-43 aggregates deplete nuclear endogenous TDP-43 and induce cytotoxicity. Collectively, these findings highlight the local cytoplasmic concentration of TDP-43 and stress exposure as key determinants in the onset of TDP-43 proteinopathy, providing a relevant model to study pathological TDP-43 aggregation.},
}

@article {pmid41614057,
year = {2025},
author = {Subramani, NK and Venugopal, S and Rajan, AP},
title = {An integrated subtractive genomics and immunoinformatic approach for designing a multi-epitope peptide vaccine against methicillin-resistant Staphylococcus aureus.},
journal = {Frontiers in bioinformatics},
volume = {5},
number = {},
pages = {1745495},
pmid = {41614057},
issn = {2673-7647},
abstract = {INTRODUCTION: MRSA is a multi-drug-resistant bacteria responsible for severe infections that has become a major health concern. Due to constraints of traditional methods, there is a need for developing a new approach to prevent the MRSA-related infections by targeting key pathogens.

METHODS: Initially, the subtractive genomics was applied to the MRSA proteome to identify non-homologous, essential, and virulence targets using comparative BLAST-based screening. Further, immunoinformatic tools were employed for B- and T-cell epitope prediction and vaccine construction with appropriate adjuvants and linkers, followed by immune simulation and molecular docking with immune receptors.

RESULTS: Comparative metabolic pathway analysis identified 294 MRSA pathway proteins, with acetolactate synthase (ALS) as a non-homologous, essential, and virulent protein that is involved in the branched amino acid biosynthesis pathway. The constructed ALS vaccine consists of 3 B-cell and 19 T-cell epitopes exhibited stable immunological features with 97.55% global population coverage. Molecular docking revealed that ALS exhibited a superior binding affinity with the TLR4 receptor (-1,438.7 kcal/mol) than the TLR2 receptor (-1,103.5 kcal/mol), which was further confirmed by high structural stability and compactness analysis. Immune simulations also exhibited elevated IgM, IgG subtypes, and cytokine productions, suggesting a robust humoral and cellular immunity.

DISCUSSION: Identified ALS highlights its biological relevance in MRSA survival. The stability predictions with TLR4 suggested effective activation of innate immunity that may enhance antigen presentation and downstream adaptive immunity. The validation of the ALS vaccine's safety and immunogenicity further requires comprehensive in vitro and in vivo examinations.

CONCLUSION: Thus, ALS is recognized as a promising MRSA vaccine candidate and has the potential to activate immune responses effectively.},
}

@article {pmid41613680,
year = {2025},
author = {Yamazaki, J and Hideyama, T and Teramoto, S and Kato, H and Aizawa, H and Kwak, S and Terashi, H},
title = {Age-Related Changes in Matrix Metalloproteinase-9 Expression in Spinal Motor Neurons of Normal Mice.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e100305},
pmid = {41613680},
issn = {2168-8184},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving the degeneration of upper motor neurons (UMNs) and lower motor neurons (LMNs). Although the cause of motor neuron (MN) degeneration in patients with ALS remains unknown, certain MN types (such as oculomotor neurons) and MNs within the Onuf (Onuf-Mannen) nucleus are preserved until the terminal stage. We previously generated mice with a selective knockout of adenosine deaminase acting on RNA 2 (ADAR2) in cholinergic neurons (ADAR2[flox/flox] /vesicular acetylcholine transporter (VAChT)-Cre.Fast; AR2). AR2 mice exhibit slow progressive loss of LMNs accompanied by TAR DNA-binding protein 43 (TDP-43) pathology against a background of insufficient editing at the GluA2 glutamine/arginine (Q/R) site due to ADAR2 deficiency. This model confirmed that insufficient editing at the GluA2 Q/R site, due to reduced ADAR2 activity, contributes to the pathogenesis of ALS. Furthermore, in AR2 mice, more frequent death of fast-fatigable motor neurons (FF MNs) was observed owing to differences in vulnerability under ADAR2-deficient conditions. Similar changes were observed during normal aging in the control mice. These findings suggest that investigating the characteristics of FF MNs may be useful for analyzing neuronal death in ALS. Recently, matrix metalloproteinase-9 (MMP-9), a marker of FF MNs, was reported to induce neurodegeneration. However, the distribution of MMP-9 in normal spinal MNs and its age-related changes remain unclear. Therefore, we investigated the MMP-9 expression patterns in normal mice at six and 12 months of age. In the present study, the number of MNs in the anterior horn (AH) decreased with age, as did the number of MMP-9-positive MNs. Furthermore, as aging has been shown to induce the abnormal localization of TDP-43 in MMP-9-positive MNs, these MNs were considered vulnerable to degeneration. These findings suggest that MMP-9 not only functions as a marker for FF MNs but may also act as a potentially useful marker for MNs prone to degeneration with TDP-43 pathology, or for early degeneration in both physiological aging and age-related diseases, including ALS. Future investigations of MMP-9 expression in patients with ALS and in ALS mouse models are considered useful for elucidating ALS pathogenesis.},
}

@article {pmid41613245,
year = {2026},
author = {Aronsen, J},
title = {You have ALS: a nurse's revolt against despair.},
journal = {Journal of research in nursing : JRN},
volume = {},
number = {},
pages = {17449871251407834},
doi = {10.1177/17449871251407834},
pmid = {41613245},
issn = {1744-988X},
}

@article {pmid41613186,
year = {2025},
author = {An, W and Jin, Z and Li, Y},
title = {Dual role of exosomes in neurodegenerative diseases: a molecular bridge between neuroinflammation and transmission of pathological proteins.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1708655},
pmid = {41613186},
issn = {1664-2295},
abstract = {Neurodegenerative diseases (NDDs) are complex disorders characterized by the progressive loss of neuronal function. Their pathological mechanisms involve multiple levels, including neuroinflammation, abnormal protein aggregation, and disrupted cell signaling. Diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), multiple sclerosis (MS), and prion diseases not only severely impact patients' quality of life but also pose significant challenges for medical research due to their complex pathogenesis and the lack of effective treatments. In recent years, extracellular vesicles (EVs), particularly exosomes, have garnered increasing attention for their critical role in cell-to-cell communication. Exosomes are membrane-enclosed nanovesicles approximately 30-150 nm in diameter that can carry proteins, lipids, nucleic acids, and other bioactive molecules, influencing recipient cells through paracrine or distant signaling. This review aims to summarize the roles of exosomes as mediators of neuroinflammation and as vehicles for intercellular transmission of pathogenic proteins in neurodegenerative diseases.},
}

@article {pmid41612503,
year = {2026},
author = {Takahashi, K and Kato, C and Ueda, K and Nakamura, S and Ozawa, F and Moritoki, N and Shibata, S and Takahashi, S and Morimoto, S and Okano, H},
title = {Diagnostic potential of cryptic exon-derived peptides in serum extracellular vesicles for sporadic amyotrophic lateral sclerosis.},
journal = {Inflammation and regeneration},
volume = {},
number = {},
pages = {},
doi = {10.1186/s41232-026-00404-w},
pmid = {41612503},
issn = {1880-9693},
support = {JP21H05278//Japan Society for the Promotion of Science/ ; JP22K15736//Japan Society for the Promotion of Science/ ; JP25H00007//Japan Society for the Promotion of Science/ ; JP23bm1123046//Japan Agency for Medical Research and Development/ ; JP23kk0305024//Japan Agency for Medical Research and Development/ ; JP25ek0109811//Japan Agency for Medical Research and Development/ ; JP21wm0425009//Japan Agency for Medical Research and Development/ ; JP22bm0804003//Japan Agency for Medical Research and Development/ ; JP22ek0109616//Japan Agency for Medical Research and Development/ ; JP23bm1423002//Japan Agency for Medical Research and Development/ ; JP25wm0625519//Japan Agency for Medical Research and Development/ ; 2024A04//Japan Intractable Diseases（Nanbyo）Research Foundation/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration and loss of upper and lower motor neurons, with approximately 90% of cases being sporadic (sporadic ALS, SALS). A reliable diagnostic biomarker remains an unmet clinical need in SALS, with misdiagnosis and diagnostic delay hindering early management. The mislocalization of the RNA-binding protein TDP-43 (encoded by TARDBP), a pathological hallmark of SALS, could lead to aberrant splicing that produces transcripts with cryptic exons and, consequently, cryptic peptides. This study proposes cryptic peptides in serum extracellular vesicles as a novel candidate diagnostic biomarker of SALS. We included 10 healthy controls and 20 patients with SALS and quantified cryptic peptides predicted from cryptic exon sequences using mass spectrometry-based proteomics. Cryptic peptides from four proteins (RANBP1, IGLON5, ACTN1, ALPK2) were detected in participants, with the IGLON5 cryptic peptide detected significantly more frequently in SALS than in HC (adjusted P = 0.044). The number of detected cryptic peptides classified SALS and healthy controls with acceptable performance (area under the curve = 0.82). In conclusion, cryptic peptides could have diagnostic performance for SALS, warranting further validation.},
}

@article {pmid41612406,
year = {2026},
author = {Bigi, A and Chiti, F},
title = {Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.},
journal = {Genome biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13059-026-03956-9},
pmid = {41612406},
issn = {1474-760X},
support = {#NEXTGENERATIONEU (NGEU) - National Recovery and Resilience Plan (NRRP), Investment PE8─Project Age-It: "Ageing Well in an Ageing Society" (D.R. 1557 11.10.2022).//Ministero dell'Università e della Ricerca/ ; Fondi di Ateneo RICATEN 2024 and RICATEN 2025//Università degli Studi di Firenze/ ; Fondi di Ateneo RICATEN 2023, RICATEN 2024 and RICATEN 2025//Università degli Studi di Firenze/ ; },
abstract = {Phase separation is an important process in biology associated with formation of membraneless organelles but possibly related to the emergence of solid inclusions. TDP-43 is a largely studied paradigmatic case, as it forms neuronal cytoplasmic inclusions in neurodegenerative diseases and is an essential component of many membraneless organelles. Here, we review the physicochemical fundamentals of liquid-liquid phase separation (LLPS) of TDP-43 and its fragments in vitro, showing that full-length TDP-43 requires RNA or chaperones to form stable liquid droplets. We describe TDP-43-containing membraneless organelles and the debate on whether these assemblies represent reservoirs for pathological solid inclusion formation.},
}

@article {pmid41611549,
year = {2026},
author = {Santurtún, A and Medín, P and Riancho, JA and Santiago-Setién, M and Ortiz, F and López de Munain, A and Almendra, R and Riancho, J},
title = {Corrigendum to "Temporo-spatial analysis of amyotrophic lateral sclerosis in Spain: Altitude and land use as new determinants of the disease" [Sci. Total Environ., 957 (2024), 177796].},
journal = {The Science of the total environment},
volume = {},
number = {},
pages = {181474},
doi = {10.1016/j.scitotenv.2026.181474},
pmid = {41611549},
issn = {1879-1026},
}

@article {pmid41611468,
year = {2026},
author = {Ivankov, DN and Zorin, EM},
title = {Sign epistasis can be absent in multi-peaked landscapes with neutral mutations.},
journal = {Genome biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/gbe/evag024},
pmid = {41611468},
issn = {1759-6653},
abstract = {Fitness landscapes provide a rigorous mathematical framework for analyzing evolutionary dynamics, including the study of epistasis, the main obstacle to predicting phenotype from genotype. In 2011, Poelwijk et al. formulated a foundational theorem stating that in any multi-peaked fitness landscape, "at least two mutations exhibit reciprocal sign epistasis" (Poelwijk et al., J. Theor. Biol., 272:141). The proof relied on the implicit assumption that neutral mutations are absent, commonly accepted in theoretical studies in evolutionary biology. In this study, we extend Poelwijk et al.'s analysis by incorporating genotypes with equal fitness, specifically, accounting for neutral mutations. We demonstrate that when neutral mutations are considered, conventional pairwise reciprocal sign epistasis (RSE) may be entirely absent from a multi-peaked landscape. Instead, RSE is guaranteed only when considering "distant" RSE defined through composite mutations, wherein groups of mutations are treated collectively across all their possible combinations. Applying these concepts to empirical fitness landscapes faces a practical limitation: phenotypic measurements contain experimental noise, making some mutational effects statistically indistinguishable from zero. Under such conditions, statistically significant detection of RSE in multi-peaked landscapes may be impossible even when composite mutations are considered. Theoretically, our findings imply that in the presence of neutral mutations, compensatory mutations in a multi-peaked fitness landscape need not be adjacent; rather, compensation can occur following one or more neutral steps along an evolutionary path. Practically, in real-world scenarios where fitness measurements contain uncertainty, there may be a fundamental technical limitation to detecting RSE in a statistically significant manner within multi-peaked landscapes.},
}

@article {pmid41611003,
year = {2026},
author = {Flose, BR and Silva, KCN and Juliano, A and Trevisani, VFM and França, CN and Corral, MA and da Silva Nali, LH and Shio, MT},
title = {Antibody response against HERV-K polymerase and envelope by patients with multiple sclerosis.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {},
number = {},
pages = {120870},
doi = {10.1016/j.cca.2026.120870},
pmid = {41611003},
issn = {1873-3492},
abstract = {INTRODUCTION: Human Endogenous Retroviruses (HERVs) are viruses that have infected germ cells of our ancestors millions of years ago and compose 8% of human genome. The expression of HERVs is associated with neurological disorders such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). The humoral immune response against peptides from the envelope proteins, but not to polymerase, of HERV-K has been previously described. The aim of this study is to evaluate anti-HERV- K polymerase (pol) humoral response in patients with MS.

METHODS: GenBank platform were used to select peptides with similarity above 50%, comparing HERV sequences (K or W) with the protein Myelin Oligodendrocyte Glycoprotein (MOG). The synthesized peptides were used in the ELISA test for anti-HERV-K (pol - polymerase) and W (env - envelope) antibodies in serum of patients with MS (31) and healthy population (54) with no history of autoimmune diseases.

RESULTS: One peptide (pep) related to HERV-W env and 8 peptides of HERV-K env or pol were selected and synthesized. Validation of the indirect ELISA with sera from MS patients showed that there was immunoreactivity for all peptides compared to healthy population (p < 0.0001). HERV-K env peptide 5 (WSGNQTLETRD) and 7 (ECVANSAVIL) showed the highest values of sensitivity and specificity, as well as diagnostic accuracy with 95.16% and 96.77%, respectively. HERV-K pol peptides 6 (LGIPTYAM), 8 (VTHVPSFR) and 9 (STVKTFTYLD) have demonstrated high values of accuracy 82.26, 80.65 and 82.26, respectively. These cutoff values were used to calculate the ELISA index - EI. The MS samples had a higher EI compared to the healthy population for almost all peptides of HERV-K pol (p < 0.001).

CONCLUSION: The present work showed a humoral response related to HERV-K pol and env, as well as HERV-W env, by patients with MS. All diagnostic parameters are appreciable, which makes it possible to use this tool to better understand the mechanisms related to viral immunology in patients.},
}

@article {pmid41610293,
year = {2026},
author = {Gauld, N and Cleland, J and Buchanan, S and Hikaka, J and Frampton, C and Buetow, S},
title = {Riluzole use and reasons for non-use in people with amyotrophic lateral sclerosis in Aotearoa New Zealand.},
journal = {The New Zealand medical journal},
volume = {139},
number = {1628},
pages = {50-57},
doi = {10.26635/6965.7238},
pmid = {41610293},
issn = {1175-8716},
support = {//This research was funded by a Health Research Council Research Activation Grant, a Motor Neurone Disease New Zealand grant and some voluntary time by the authors./ ; },
mesh = {Humans ; *Riluzole/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy ; New Zealand ; Male ; Female ; Middle Aged ; Aged ; *Neuroprotective Agents/therapeutic use ; Surveys and Questionnaires ; Adult ; },
abstract = {UNLABELLED: Amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND), is a neurodegenerative condition with typically short life expectancy. Riluzole, the only survival prolonging medication funded in Aotearoa New Zealand, has high uptake in other developed countries.

AIMS: To quantify riluzole use in New Zealand, identify factors associated with its use and explore reasons for non-use.

METHODS: In 2025, people in New Zealand diagnosed with MND were invited to self-complete questionnaires. Data were collected via Qualtrics, exported to Excel and analysed using descriptive and inferential statistics. Respondents with progressive muscular atrophy or primary lateral sclerosis diagnoses were excluded from this analysis.

RESULTS: Of 115 respondents, 55 (48%) were currently taking riluzole, 14 (12%) had taken it previously and 42 (36%) had never taken it. Common reasons for non-use included riluzole not being offered and concerns about lack of effectiveness and/or side effects. Uptake was lower with bulbar onset than limb onset (p<0.05).

CONCLUSIONS: People with ALS in New Zealand have low uptake of riluzole, despite its survival benefits. Prescribers and people with ALS need up-to-date information about riluzole's benefit-risk profile to increase uptake and confidence in prescription and use. Liquid riluzole is needed in New Zealand to aid uptake.},
}

Humans
*Riluzole/therapeutic use
*Amyotrophic Lateral Sclerosis/drug therapy
New Zealand
Male
Female
Middle Aged
Aged
*Neuroprotective Agents/therapeutic use
Surveys and Questionnaires
Adult

@article {pmid41610283,
year = {2026},
author = {Hayes, JM and Fornagiel, M and Kipust, A and Peters, GA and Goldberg, SA and Cash, RE},
title = {Statewide Emergency Medical Services Protocols for Field-Initiated Blood Resuscitation.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/10903127.2026.2623431},
pmid = {41610283},
issn = {1545-0066},
abstract = {OBJECTIVES: Prehospital blood transfusion by emergency medical services (EMS) is associated with improved outcomes in trauma patients, but little is known about the statewide protocols that influence the availability and use of prehospital blood. This study aimed to describe statewide EMS protocols regarding field-initiated prehospital blood and blood product transfusion across the U.S.

METHODS: This was a cross-sectional analysis of publicly available statewide EMS protocols pertaining to field-initiated blood or blood product use during ground transport by advanced life support (ALS) clinicians. We excluded protocols specific to critical care or interfacility transport. We used a standardized data collection tool to compare clinical indications, blood product type, and considerations for pediatrics and biologically female patients who may bear children in the future. Descriptive statistics were used to describe the protocols.

RESULTS: We identified 31 states and the District of Columbia with publicly available statewide EMS protocols. Thirteen (42%) of these protocols allowed for field-initiated prehospital blood transfusion. There was variability regarding recommendations for transfusion indications and the details of administration in the protocols. All protocols allowed for transfusion in traumatic emergencies, and nine (69%) allowed for transfusion in medical emergencies. Three (23%) protocols specifically recommended low titer group O whole blood, and three (23%) protocols allowed transfusion during cardiac arrest. Nine (69%) protocols allowed for transfusion in pediatric patients. Only four (31%) protocols included special considerations for transfusing blood to biologically female patients.

CONCLUSIONS: While most statewide EMS protocols in the US did not include field-initiated blood transfusion, the protocols that do exist vary widely. With the increasing implementation of prehospital blood programs, these findings suggest an opportunity to provide more robust evidence-based guidelines for prehospital blood transfusion to improve patient care and outcomes.},
}

@article {pmid41609605,
year = {2026},
author = {Bridges, AJ and Fradley, MF and Karlsson, ME and Zielinski, MJ},
title = {Centering the client in PTSD treatments: Commentary on Rubenstein et al. (2024).},
journal = {The American psychologist},
volume = {81},
number = {1},
pages = {109-111},
doi = {10.1037/amp0001480},
pmid = {41609605},
issn = {1935-990X},
mesh = {Humans ; *Stress Disorders, Post-Traumatic/therapy ; *Implosive Therapy/methods ; },
abstract = {We offer commentary examining conclusions that may be drawn from Rubenstein et al.'s (2024) perspective on the need for exposure-based posttraumatic stress disorder (PTSD) treatments. Here, we employ our shared expertise in implementing and evaluating exposure-based group therapy to reconsider the following impressions garnered from the referenced article: (a) exposure is not necessary for successful PTSD treatment; (b) clients do not want to talk about traumatic memories and will drop out of treatment; (c) exposure may be destabilizing to clients; and (d) clients will spontaneously expose, rendering exposure in therapy unnecessary. In this commentary, we focus on data that center clients' perspectives and acknowledge client choice in the use of exposure. As did Rubenstein et al. (2024), we conclude that exposure is useful for a diverse range of clients, frequently preferred over other forms of treatment, and highly effective for treatment of PTSD. We support efforts to increase access to efficacious PTSD treatments, urging that exposure-based treatments be offered to clients alongside other evidence-based therapies. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

Humans
*Stress Disorders, Post-Traumatic/therapy
*Implosive Therapy/methods

@article {pmid41609580,
year = {2026},
author = {Purvinsh, Y and Matveyenka, M and Kurouski, D},
title = {Elucidation of Molecular Mechanisms of Lipid-Altered Cytotoxicity of TDP-43 Fibrils.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00934},
pmid = {41609580},
issn = {1948-7193},
abstract = {Progressive aggregation of TAR DNA-binding protein 43 (TDP-43) is a hallmark of numerous neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer's disease, and limbic predominant age-related TDP-43 encephalopathy (LATE). This highly conserved nuclear RNA/DNA-binding protein is involved in the regulation of RNA processing. The C-terminal domain (CTD) of TDP-43 plays a key role in protein solubility, cellular localization, and protein-protein interactions. CTD is rich in glycine, glutamine, and asparagine, which facilitate TDP-43 aggregation into amyloid oligomers and fibrils observed in the brain. In this study, we examine the role of lipid bilayers in the aggregation properties of the CTD of TDP-43. We found that lipid bilayers composed of anionic phosphatidylserine and cardiolipin accelerated TDP-43 aggregation. Although lipids did not alter the secondary structure, they altered the cytotoxicity that TDP-43 fibrils exerted to rat dopaminergic cells. Using molecular methods, we showed that TDP-43 fibrils damage cell endosomes. This causes aggregate leakage into the cytosol, where TDP-43 fibrils impair cell autophagy, simultaneously triggering a severe unfolded protein response in the endoplasmic reticulum. Our results indicate that TDP-43 aggregation may be linked to pathological changes in the lipid profiles of neurons.},
}

@article {pmid41607759,
year = {2026},
author = {Kirkik, D and Ozadenc, HM and Kalkanli Tas, S},
title = {Machine learning approaches to early detection of delayed wound healing following gastric cancer surgery.},
journal = {World journal of gastrointestinal oncology},
volume = {18},
number = {1},
pages = {114499},
pmid = {41607759},
issn = {1948-5204},
abstract = {Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization, increases costs, and undermines patient recovery. In An et al's recent study, the authors present a machine learning-based risk prediction approach using routinely available clinical and laboratory parameters. Among the evaluated algorithms, a decision tree model demonstrated excellent discrimination, achieving an area under the curve of 0.951 in the validation set and notably identifying all true cases of delayed wound healing at the Youden index threshold. The inclusion of variables such as drainage duration, preoperative white blood cell and neutrophil counts, alongside age and sex, highlights the pragmatic appeal of the model for early postoperative monitoring. Nevertheless, several aspects warrant critical reflection, including the reliance on a postoperative variable (drainage duration), internal validation only, and certain reporting inconsistencies. This letter underscores both the promise and the limitations of adopting interpretable machine learning models in perioperative care. We advocate for transparent reporting, external validation, and careful consideration of clinically actionable timepoints before integration into practice. Ultimately, this work represents a valuable step toward precision risk stratification in gastric cancer surgery, and sets the stage for multicenter, prospective evaluations.},
}

@article {pmid41607656,
year = {2025},
author = {Ha, LL and Mitra, S and Ho, DT and Fillingham, B and Berry, JD and Swoboda, KJ and Alves, CRR},
title = {Circulating Tau Profiles in Pediatric and Adult Patients with Spinal Muscular Atrophy.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41607656},
abstract = {OBJECTIVE: To determine alterations in circulating Tau and phosphorylated Tau (pTau) profiles in pediatric and adult patients with spinal muscular atrophy (SMA).

METHODS: Circulating total Tau, pTau-181, pTau-217, pTau-262, and pTau-396 concentrations were measured across three cohorts: 1) adults including healthy controls, SMA patients, and ALS patients; 2) pediatric SMA patients and age-matched controls; and 3) pediatric SMA patients treated with onasemnogene abeparvovec.

RESULTS: Distinct alterations in circulating Tau species were detected in adult SMA and ALS. Among all measurements, pTau-262 emerged as the only species specifically elevated in adult SMA, while total Tau levels were comparable between adult SMA and controls but significantly increased in ALS. Tau alterations were not consistently observed in pediatric SMA, although a small subset showed elevated levels, underscoring the value of individualized biomarker monitoring upon diagnosis. In gene-therapy-treated infants, Tau levels increased transiently several weeks after onasemnogene abeparvovec injection, paralleling previously described neurofilament kinetics and suggesting acute, treatment-associated neuronal stress.

CONCLUSIONS: Circulating Tau, particularly pTau-262, may serve as a disease-relevant biomarker in adult SMA, while pediatric profiles appear more heterogeneous. Transient Tau elevations after gene therapy may reflect acute neuronal vulnerability and warrant further investigation.},
}

@article {pmid41606993,
year = {2026},
author = {Lindström, L and Ahlsson, F and Axelsson, O and Granfors, M and Lampa, E and Nelander, M and Wikström, AK},
title = {Differences in prediction of adverse perinatal outcome in term pregnancies by choice of fetal growth reference: A validation study.},
journal = {Acta obstetricia et gynecologica Scandinavica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aogs.70136},
pmid = {41606993},
issn = {1600-0412},
support = {LUL-964880//Region Uppsala/ ; //Födelsefonden/ ; },
abstract = {INTRODUCTION: Our objectives were to evaluate the association between fetal growth abnormalities and adverse perinatal outcomes in term pregnancies using four different fetal growth references: the recently published Swedish references by Lindström et al., the currently used Swedish references by Maršál et al., and the international standards by the WHO and INTERGROWTH-21st (IG21st). The study aimed to evaluate the performance of each reference and determine which reference most accurately identifies small for gestational age (SGA) infants at risk of perinatal mortality and morbidity.

MATERIAL AND METHODS: This population-based cohort study included 1 126 059 singleton term births in Sweden from 2010 to 2020. Data were obtained from national registers, including the Swedish Medical Birth Register and the Swedish Neonatal Quality Register. Birthweight centiles were calculated using each growth reference. Adverse perinatal outcomes were categorized by severity and included stillbirth, neonatal death, and serious neonatal morbidity. Logistic regression models were used to assess predictive performance, and sensitivity and false positive rates (FPR) were calculated for SGA thresholds (<3rd and <10th centiles).

RESULTS: The distribution of birthweight centiles varied significantly across references. For SGA <3rd centile, the rate ranged from 9.6% for Lindström, 2.5% for Maršál, 1.9% for WHO, to 0.7% for IG21st. All references showed similar overall predictive performance (C-index ≈ 0.67) but with different discriminatory ability. The predicted risk of perinatal death increased at lower centiles for the Lindström reference than for the Maršál and WHO references, and at higher centiles for the IG21st reference. The Lindström reference identified the highest proportion of infants as SGA and had the highest sensitivity but also the highest FPR for detecting adverse outcomes. The IG21st reference classified the smallest proportion as SGA, resulting in the lowest sensitivity and FPR.

CONCLUSIONS: While all fetal growth references showed comparable predictive ability for adverse perinatal outcomes, they differed substantially in sensitivity and FPR. When the top priority is to identify as many at-risk fetuses as possible, Lindström et al.'s reference seems to be the best choice. However, when the top priority is a balanced sensitivity versus FPR, the WHO reference seems most suitable for clinical practice in this population of term births.},
}

@article {pmid41606859,
year = {2025},
author = {Dehbasteh, M and Naderi Tehrani, N and Parastar, H},
title = {Multivariate curve resolution followed by partial least squares-discriminant analysis combined with Vis-NIR hyperspectral imaging for rice authentication.},
journal = {Food research international (Ottawa, Ont.)},
volume = {221},
number = {Pt 1},
pages = {117266},
doi = {10.1016/j.foodres.2025.117266},
pmid = {41606859},
issn = {1873-7145},
mesh = {*Oryza/chemistry/classification ; Least-Squares Analysis ; Discriminant Analysis ; *Hyperspectral Imaging/methods ; Spectroscopy, Near-Infrared/methods ; Iran ; Multivariate Analysis ; *Food Contamination/analysis ; Principal Component Analysis ; },
abstract = {Rice serves as a staple food for nearly half the global population, especially in Asia, where it is a major agricultural commodity. Nonetheless, deceptive practices, like blending premium and inferior rice varieties and selling them at inflated prices, present a considerable challenge to the industry. This study aims to authenticate rice samples using visible-short wavelength hyperspectral imaging (Vis-SWNIR HSI). To achieve this goal, 163 intact rice samples were sourced from three northern provinces of Iran (Gilan, Mazandaran and Golestan), including four different varieties (Hashemi, Shiroodi, Fajr and Neda). Samples were scanned by HSI device to record their cubic data. The HSI data of different samples were used in a column-wise augmented data matrix with pixels of different samples as rows and wavelengths as columns. The pure spatial (distribution maps) and spectral profiles of desired components were extracted using multivariate curve resolution-alternating least squares (MCR-ALS). As low-quality rice samples are considered adulterants for high-quality samples, the obtained data were used to differentiate samples by their origin as well as in adultertation detection. To the best of our knowledge, the MCR-ALS algorithm has not been used for rice authentication before using their intact forms. Further chemometric analyses, including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), were applied to the spectral-resolved profiles of samples. This enables us to discriminate three different origins and four varieties of rice samples, as well as for adulteration detection, providing classification accuracies of 94.4 %, 82.75 % and 100 % in the prediction sets, respectively. Such an outcome indicates the practical feasibility of imaging methods for rapid, cost-effective and non-invasive food authentication purposes.},
}

*Oryza/chemistry/classification
Least-Squares Analysis
Discriminant Analysis
*Hyperspectral Imaging/methods
Spectroscopy, Near-Infrared/methods
Iran
Multivariate Analysis
*Food Contamination/analysis
Principal Component Analysis

@article {pmid41605610,
year = {2026},
author = {Oreskovic, E and Petzold, A and Petropoulos, IN and Hau, S},
title = {Corneal confocal microscopy as a paraclinical test in neurodegenerative disease: a scoping review.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328181},
pmid = {41605610},
issn = {1468-2079},
abstract = {Corneal confocal microscopy (CCM) is a non-invasive imaging technique that enables quantification of the corneal sub-basal nerve plexus and has emerged as a potential surrogate biomarker for peripheral neurodegeneration. This scoping review evaluated current evidence on the use of CCM in assessing corneal nerve fibre changes across neurodegenerative diseases (NDDs) and explored its potential as a paraclinical diagnostic and monitoring tool. A comprehensive search of PubMed and Scopus was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines to identify studies reporting quantitative CCM metrics, including corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL). Both cross-sectional and longitudinal studies of patients with NDDs were included, and findings were narratively synthesised. 50 studies were included: Parkinson's disease (n=13), multiple sclerosis (n=11), cerebrovascular accidents (n=7), post-COVID-19 neuropathy (n=5), amyotrophic lateral sclerosis (n=4), chronic inflammatory demyelinating polyneuropathy (n=4), Alzheimer's disease (n=3), Fabry disease (n=2) and neurofibromatosis type 1 (n=1). CNFL and CNFD were consistently reduced in Parkinson's disease, multiple sclerosis, cerebrovascular accidents, amyotrophic lateral sclerosis, chronic inflammatory demyelinating polyneuropathy and post-COVID-19 neuropathy, whereas CNBD results were inconsistent. The strongest evidence supported the role of CCM in Parkinson's disease and multiple sclerosis. CNFL and CNFD emerged as the most reliable CCM-derived metrics across NDDs, supporting their potential as objective biomarkers for neurodegeneration. While findings support the potential of CCM as a paraclinical diagnostic tool, methodological heterogeneity in image acquisition, analysis software and study design limited comparability. Standardised imaging and analysis protocols are needed to enable broader clinical application and validation across NDDs.},
}

@article {pmid41605460,
year = {2026},
author = {Martínez-Alesón, P and Benito-Casado, C and Fernández-Martos, CM and Polanco Mora, MJ},
title = {Pleiotrophin/Midkine Pathway Is Dysregulated in a TDP-43[A315T] Mouse Model of Amyotrophic Lateral Sclerosis (ALS).},
journal = {Neuropathology : official journal of the Japanese Society of Neuropathology},
volume = {46},
number = {1},
pages = {e70044},
doi = {10.1111/neup.70044},
pmid = {41605460},
issn = {1440-1789},
support = {FUSPBS-PPC03/2018//University San Pablo CEU-Santander precompetitive grants/ ; SBPLY/17/180501/000303//Junta de Comunidades de Castilla-la Mancha/ ; PIPF-2023/SAL-GL-29613//Consejería de Educación, Ciencia y Universidades Comunidad de Madrid/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Midkine/metabolism ; *Cytokines/metabolism ; Disease Models, Animal ; Mice ; Signal Transduction/physiology ; *Carrier Proteins/metabolism ; DNA-Binding Proteins/genetics ; Spinal Cord/metabolism/pathology ; Mice, Transgenic ; Receptor-Like Protein Tyrosine Phosphatases, Class 5/metabolism ; Motor Neurons/metabolism/pathology ; Male ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease (MND) characterized by progressive degeneration of both upper and lower motor neurons, along with skeletal muscles innervated by them. The identification of key molecules involved in disease pathology remains crucial for ALS, as no curative treatment is currently available. Pleiotrophin (PTN) and midkine (MK) are closely related, heparin-binding cytokines with overlapping effects. These molecules have been shown to be neuroprotective by modulating neuroinflammation, supporting neuronal survival, growth, and differentiation, and enhancing synaptic strength and plasticity. Despite their reported neuroprotective properties, the involvement of PTN and MK signaling in ALS has not been previously investigated. In this study, we characterized the expression of the PTN/MK pathway in the lumbar spinal cords (SCs) of TDP-43[A315T] mice across different disease stages. We report a significant upregulation of Ptn, Mdk, and its receptor protein tyrosine phosphatase zeta (Ptprz1) mRNA levels at end-stage of disease in the lumbar SC of TDP-43[A315T] mice compared with age-matched wild-type littermates. Protein levels of PTN and MK were also upregulated at end-stage of disease. By immunofluorescence analysis, we also observed an upregulation of the immunostaining of both cytokines in neurons, astrocytes, microglia, and pericytes-like structures at end-stage of disease in the SC of TDP-43[A315T] mice. These findings open a new avenue to further study the potential role of the PTN/MK signaling axis in the pathogenesis of ALS. Trial Registration: Animal Ethics Committee of the Hospital Nacional de Parapléjicos in Toledo (Spain): Approval No. 26/OH 2018.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
*Midkine/metabolism
*Cytokines/metabolism
Disease Models, Animal
Mice
Signal Transduction/physiology
*Carrier Proteins/metabolism
DNA-Binding Proteins/genetics
Spinal Cord/metabolism/pathology
Mice, Transgenic
Receptor-Like Protein Tyrosine Phosphatases, Class 5/metabolism
Motor Neurons/metabolism/pathology
Male

@article {pmid41604971,
year = {2026},
author = {Ahamad, S and Akshinthala, P and Fazal, F and Sah, GK and Khan, MH and Upadhyay, A and Bhat, SA and Hussain, MK},
title = {Small-molecule-based activation of Wnt/β-catenin signaling: An underexplored yet promising strategy for neuroprotection.},
journal = {Bioorganic chemistry},
volume = {170},
number = {},
pages = {109540},
doi = {10.1016/j.bioorg.2026.109540},
pmid = {41604971},
issn = {1090-2120},
abstract = {The Wnt/β-catenin pathway regulates key processes such as neurogenesis, synaptic plasticity, and neuroinflammation, each disrupted in neurodegenerative disorders like AD, PD, ALS, and stroke. Small molecules have shown potential to restore this signaling axis and confer neuroprotection. While these molecules modulate Wnt activity, none has achieved FDA approval, primarily due to poor brain permeability, off-target effects, and insufficient biomarker-based validation. Moreover, current strategies remain disproportionately focused on GSK-3β, with other viable targets, such as DKK1, NOTUM, SFRP-1, sclerostin, and Dvl-CXXC5 or Axin-β-catenin interactions, largely underexplored. Natural products, particularly flavonoids and diterpenoids, offer valuable scaffolds; however, their SAR remain poorly characterized, and promising synthetic leads often lack further development. This review highlights recent pharmacological advances, emerging molecular targets, and key translational barriers. Future success will depend on optimizing pharmacokinetics, improving brain-targeted delivery, and integrating biomarker-driven strategies into clinical trial design.},
}

@article {pmid41604235,
year = {2026},
author = {Al-Ameer, HJ and Basheer, NM and H, M and Shankhyan, A and Panigrahi, R and Arora, V and Azizjanov, K and Eshchanov, E and Ataullaev, Z},
title = {Neuroimmune Cross-Talk and Multilevel Cascades in Fentanyl Toxicity: Interplay of Hypoxic Stress, Glial Activation, and Synaptic Dysregulation in Systems-Level Neurodegeneration.},
journal = {Journal of applied toxicology : JAT},
volume = {},
number = {},
pages = {},
doi = {10.1002/jat.70069},
pmid = {41604235},
issn = {1099-1263},
abstract = {Fentanyl, an ultra-potent synthetic opioid, has traditionally been characterized by its acute toxic effects, particularly respiratory depression. However, accumulating research indicates that its neurobiological influence extends far beyond its short pharmacological window, intersecting with several core mechanisms implicated in major neurodegenerative disorders. This review integrates multiscale evidence to propose a unified conceptual framework in which fentanyl may function not only as an acute neurotoxin but also as a putative accelerator of long-term neurodegenerative vulnerability. Drawing from molecular signaling, cellular stress pathways, glial-neuronal cross-talk, neurovascular regulation, synaptic architecture, and large-scale neural networks, we highlight fentanyl's capacity to trigger a convergent cascade encompassing hypoxic-metabolic reprogramming, mitochondrial fragmentation, TLR4-NF-κB-driven inflammation, NLRP3 inflammasome activation, complement-mediated synaptic pruning, astrocytic EAAT2 downregulation, and blood-brain barrier compromise. These alterations propagate through recursive cross-talk loops that progressively diminish neuronal resilience, destabilize oscillatory coherence, and weaken circuit-level adaptability. Importantly, mechanistic overlaps with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis suggest that fentanyl exposure may be mechanistically associated with processes capable of accelerating disease onset, exacerbating progression, or unmasking latent vulnerabilities, particularly in genetically or metabolically predisposed individuals. By reframing fentanyl as a systems-level destabilizer capable of imprinting persistent neurobiological changes, this model underscores the need for comprehensive biomarker development, longitudinal risk assessment, and targeted neuroprotective interventions. The integrative framework presented herein offers a foundation for predicting the long-term neurological consequences of fentanyl exposure and calls for urgent reconsideration of its role in population-level neurodegenerative risk.},
}

@article {pmid41603250,
year = {2026},
author = {Naumann, M and Wierschin, TM and Kretschmer, S and Dash, BP and Held, A and Salzinger, A and Peikert, K and Karlek, A and Glaß, H and Großmann, D and Günther, R and Petri, S and Rödiger, A and Brenner, D and Pan-Montojo, F and Aronica, E and Kipp, M and Zimyanin, V and Sterneckert, J and Grehl, T and Seebacher, ND and Böckers, TM and Catanese, A and Wainger, BJ and Oeckl, P and Lee-Kirsch, MA and Hermann, A},
title = {RIG-I Mediated Neuron-Specific IFN Type 1 Signaling in FUS-ALS Induces Neurodegeneration and Offers New Biomarker-Driven Individualized Treatment Options for (FUS-)ALS.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e17135},
doi = {10.1002/advs.202417135},
pmid = {41603250},
issn = {2198-3844},
support = {CRC237 369799452/B21//German Research Foundation (DFG)/ ; CRC237 369799452/A11//German Research Foundation (DFG)/ ; CRC369 501752319/C06//German Research Foundation (DFG)/ ; 01GM2206C (GAIN)//German Federal Ministry of Education and Research (BMBF)/ ; 01GL2405H (DZKJ)//German Federal Ministry of Education and Research (BMBF)/ ; na//Stichting ALS Nederland/ ; na//Hermann und Lilly Schilling-Stiftung für Medizinische Forschung/ ; //Clinician Scientist program of the Medical Faculty of the University of Rostock (RAS)/ ; },
abstract = {Recent research demonstrated activation of the innate immune system in ALS models. This pathway can be activated by cGAS-STING sensing of cytosolic DNA that accumulates as a result of chronic DNA damage and defective mitochondria, both of which was identified as pathology in FUS-ALS. Therefore, we analyzed innate immune pathways in FUS-ALS, which revealed upregulation of interferon-stimulated genes (ISGs) and activation of the TBK1-IRF3 pathway in FUS[mut] iPSC-derived spinal motor neurons (sMNs). Accumulation of cytosolic dsRNA and its sensor RIG-I, but not MDA5, was found to be significantly upregulated in FUS[mut] sMNs, which was abolished upon siRNA-mediated knockdown of RIG-I. RIG-I was highly expressed in FUS-ALS post-mortem α-MNs. IFN treatment of FUS[wt] sMNs phenocopied the axonal degeneration of FUS[mut] sMNs. Mitochondrial transcription, a known source of dsRNA, was found to be upregulated in compartmental axonal RNAseq analysis and its inhibition reduced ISGs in FUS-ALS sMNs. The JAK-STAT inhibitor ruxolitinib alleviated the upregulated ISG expression and reversed the axonal degeneration of sMNs. Finally, we analyzed ISG expression in peripheral blood from 18 FUS-ALS patients, eight of whom had a significantly elevated interferon signature. RIG-I-mediated innate immune activation in sMNs may be an interesting novel individualized biomarker-driven therapeutic target in (FUS-) ALS. A one-sentence summary of your paper: RIG-I-mediated innate immune activation is found in FUS-ALS spinal motor neurons caused by cytosolic dsRNA accumulation due to mitochondrial transcriptional activation and is amenable to JAK-STAT inhibition and might thus be an interesting novel individualized biomarker-driven therapeutic approach in (FUS-) ALS.},
}

@article {pmid41602992,
year = {2025},
author = {Czyżewski, Ł and Petrzak-Nocuń, K and Strząska-Kliś, Z and Wyzgał, J and Religioni, U and Augustynowicz, A and Świtalski, J and Dudziński, Ł and Silczuk, A},
title = {Illness acceptance and quality of life in amyotrophic lateral sclerosis: the role of health and environmental factors.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1721044},
pmid = {41602992},
issn = {1664-2295},
abstract = {PURPOSE: To determine the extent to which illness acceptance accounts for variability in health-related quality of life (HRQoL) among adults with amyotrophic lateral sclerosis (ALS) attending a hospital-based outpatient clinic, after controlling for sociodemographic and health variables.

MATERIALS AND METHODS: We conducted a single-center, cross-sectional study in a hospital outpatient clinic. Adults with ALS completed the World Health Organization Quality of Life-BREF (WHOQOL-BREF) and the Acceptance of Illness Scale (AIS), plus a sociodemographic and health questionnaire.

RESULTS: Forty-five patients were analyzed (mean age 52 ± 14 years; 58% women). WHOQOL-BREF domain means were: physical 46.9 ± 14.1, psychological 51.2 ± 16.9, social 53.0 ± 24.6, environment 58.4 ± 18.4. Mean AIS was 20.4 ± 8.1. AIS correlated positively with all domains (r = 0.40-0.52, all p ≤ 0.006). In age- and sex-adjusted models, AIS independently predicted higher scores: physical β = 0.96 (p = 0.003), psychological β = 0.94 (p = 0.013), social β = 1.47 (p = 0.003), environment β = 1.10 (p = 0.025). Percutaneous endoscopic gastrostomy (PEG) was associated with lower physical and environment scores than oral feeding. Respiratory status differentiated physical and psychological scores. Better living conditions related to higher psychological and environment scores. Time from first symptoms to diagnosis correlated with AIS (ρ = 0.37, p = 0.014).

CONCLUSION: Illness acceptance is a robust, independent correlate of HRQoL across domains in ALS. Care should pair symptom control with brief acceptance-focused, educational, and family communication interventions, and address environmental needs. Decisions on PEG and non-invasive ventilation (NIV) should include routine dietetic, psychological, and speech-language input. Longitudinal studies should test AIS as a mediator of somatic and environmental interventions on HRQoL.},
}

@article {pmid41602910,
year = {2026},
author = {Li, Q and Zhang, G and Zheng, H and Zhao, T and Zhang, H and Zhang, Y and Luo, H and Xu, Y},
title = {ABCA1 acts as a protective modulator in amyotrophic lateral sclerosis.},
journal = {iScience},
volume = {29},
number = {1},
pages = {114320},
pmid = {41602910},
issn = {2589-0042},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease lacking reliable biomarkers and effective therapeutic targets. We performed an integrative multiscale analysis combining global epidemiology, whole-blood transcriptomics, machine learning, and Mendelian randomization (MR). We developed a nine-gene diagnostic signature (AUC = 0.75 in external validation) and identified ATP-binding cassette transporter A1 (ABCA1) as a central feature. MR analyses supported a protective causal relationship between increased ABCA1 expression and reduced ALS risk (OR = 0.93, p = 0.02). We validated this at the protein level, finding serum ABCA1 significantly elevated in an in-house ALS cohort (p = 0.006) and correlated with metabolic parameters (BMI and LDL). Spatiotemporal profiling confirmed ABCA1 upregulation in ALS patient blood and spinal cords, and progressive upregulation in ALS model mice. Collectively, we validated a diagnostic signature and identified ABCA1 as a protective, compensatory biomarker in ALS, emphasizing the link between metabolic adaptation and neurodegeneration.},
}

@article {pmid41601803,
year = {2025},
author = {An, X and Hou, D and Miao, MY and Zhou, YM and Qi, S and Zhang, L and Li, H and Zhou, JX},
title = {Noninvasive monitoring of inspiratory effort in mechanical ventilation: a dual-database bibliometric analysis from 1990 to 2025.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1747437},
pmid = {41601803},
issn = {2296-858X},
abstract = {INTRODUCTION: This study conducts a bibliometric analysis to map the intellectual structure, evolution, and emerging trends in research on airway pressure-based indexes for monitoring inspiratory effort.

METHODS: Systematic searches of the Web of Science Core Collection (WOSCC) and Pubmed were performed for publications dated between 1990 and 2025. Bibliometric parameters, including publication trends, country and affiliation contributions, author influence, journal distribution, keyword co-occurrence, and reference co-citation networks, were analyzed using Bibliometrix and CiteSpace.

RESULTS: The analysis included 291 publications from WOSCC. The annual publication output showed a near U-shaped trend, with an initial decline after the 1990s, followed by a strong resurgence after 2011. Italy was the most productive country, followed by the USA and France. The Institut National de la Sante et de la Recherche Medicale emerged as the leading institution. The journal Chest published the most articles, while the American Journal of Respiratory and Critical Care Medicine had the highest total citations. Laurent Brochard was identified as the most prolific and influential author. Keyword analysis highlighted "occlusion pressure" and "mechanical ventilation" as core themes. Reference co-citation clustering revealed major research domains, including "acute respiratory distress syndrome," "self-inflicted lung injury," and "nasal high flow." Burst detection analysis indicated that "respiratory drive," "lung injury," and "critically ill patients" are emerging research frontiers. Complementary analysis of 242 PubMed clinical studies confirmed these trends and highlighted growing clinical focus on "fluid responsiveness" and "amyotrophic lateral sclerosis."

CONCLUSION: Research on airway pressure-based indices has evolved from physiological studies into a crucial clinical tool for respiratory monitoring. The field exhibits strong international collaboration and emphasizes core areas, including acute respiratory failure and lung-protective ventilation. Analysis of clinical study data confirms these trends and highlights emerging applications in the assessment of fluid responsiveness and neuromuscular disorders. These findings support the ongoing development of personalized ventilation strategies based on monitoring respiratory effort.},
}

@article {pmid41601624,
year = {2025},
author = {Yang, J and Song, X and Yan, S and Li, Q and Yang, W},
title = {The gut microbiota influences neurodegenerative diseases through the gut-brain axis: molecular mechanisms and effects on immune function.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1739329},
pmid = {41601624},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neurodegenerative Diseases/immunology/microbiology/therapy/metabolism/etiology ; Animals ; *Brain/immunology/metabolism ; *Brain-Gut Axis/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics ; },
abstract = {The pathogenesis of neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), is complex and multifactorial. Recent studies indicate that the microbiota-gut-brain axis (MGBA) plays a crucial role in the development and progression of NDDs. The MGBA concept reveals a complex bidirectional regulatory network between the gut microbiota and the central nervous system (CNS), linking them through immune, neural, endocrine, and metabolic pathways. This review summarizes the components of the MGBA, communication pathways between gut microbiota and the brain, and mechanisms by which gut microbiota influence the onset and progression of NDDs. Finally, preclinical therapeutic approaches for NDDs are discussed, evaluating preclinical trial data for probiotics, prebiotics, and fecal microbiota transplantation.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Neurodegenerative Diseases/immunology/microbiology/therapy/metabolism/etiology
Animals
*Brain/immunology/metabolism
*Brain-Gut Axis/immunology
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Prebiotics

@article {pmid41601590,
year = {2025},
author = {Garbuzova-Davis, S and Manora, L and Borlongan, CV},
title = {Apolipoprotein A1 reduces blood-spinal cord barrier leakage, improves astrocytic coverage, and enhances motor neuron survival to restore the neurovascular unit in ALS mice.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1684694},
pmid = {41601590},
issn = {1663-4365},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive, age-related motor neuron degenerative disease with multiple causal factors. Dyslipidemia has been identified as an important pathological element. Impaired lipid protein metabolism manifests in ALS patients and in an ALS mouse model. Apolipoprotein components are the primary regulators of plasma lipid metabolism. Apolipoprotein A1 (ApoA1), a high-density lipoprotein, acts as an antioxidant and reduces inflammation, preventing blood vessel injury. However, the effects of ApoA1 upon the ALS-damaged endothelium in the CNS are unknown. The objective of the study was to determine the effect(s) of injecting ApoA1 into G93A SOD1 mice at the early symptomatic stage.

METHODS: A single dose of ApoA1 or media was systemically administered into 13-week-old G93A SOD1 male and female mice. Body weight and tests of motor function were evaluated weekly for 4 weeks post-injection. Permeability of spinal cord capillaries was determined by Evans blue (EB) fluorescent dye injected into mice at 17 weeks of age. Immunohistochemical analyses determined the statuses of glial cells and ApoA1 distributions in ALS mice cervical/lumbar spinal cords. Motor neurons in cervical/lumbar spinal cord ventral horns of ApoA1-treated and media-injected ALS mice were stained with cresyl violet for histological analyses.

RESULTS: ApoA1 injected into G93A SOD1 mice at the early symptomatic stage significantly benefited both male and female animals by (1) delaying behavioral disease progression; (2) reducing EB capillary leakage into spinal cord parenchyma; (3) lessening astrogliosis and microgliosis; (4) protein incorporation into capillary endothelium and motor neurons; and (5) improving survival of motor neurons in the spinal cord.

CONCLUSION: Our novel data showed that systemically administered ApoA1 benefited ALS mice of both sexes, likely by beneficial effects on damaged microvessels, possibly engendering restoration of neurovascular unit integrity. Moreover, an anti-inflammatory ApoA1 effect was demonstrated by the reduction of glial cell activation, potentially mitigating vascular injury. The results of our preclinical study suggest that ApoA1 may be a potential protein-mediated therapeutic for restoring vascular function. Our novel strategy may lead to future clinical trials, furthering our goal of effectively treating ALS patients.},
}

@article {pmid41601535,
year = {2025},
author = {Zhu, Y and Zhang, G and Liu, H and Yin, T and Zhang, J and Yang, Y and Bai, L and Liu, X and Fan, D and Ye, S},
title = {Depression mediates motor dysfunction's effect on sleep quality in ALS: a mediation analysis study.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1643367},
pmid = {41601535},
issn = {1662-4548},
abstract = {INTRODUCTION: Poor sleep quality affects 50-63% of Amyotrophic lateral sclerosis (ALS) patients, exacerbating disease burden and reducing quality of life. This study aimed to investigate the relationships among disease severity, depressive symptoms, and sleep quality in ALS, with a focus on the mediating effects of depression.

METHODS: Our study enrolled 408 ALS patients. Disease severity was assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R), sleep quality via the Pittsburgh Sleep Quality Index (PSQI), and psychological status using the Hamilton Depression (HAMD) and Anxiety (HAMA) scales. Statistical analyses included Spearman correlations, multivariate regression, and mediation analysis (Hayes' PROCESS macro).

RESULTS: Poor sleep quality (PSQI > 5) was observed in 54.4% of patients. Multivariate analysis found ALSFRS-R (β = -0.135, p = 0.042) and HAMD (β = 0.270, p < 0.001) correlated with sleep quality. Initial mediation analysis using the full ALSFRS-R and PSQI scales was not significant. Aimed to further explore the correlation, we derived specific subscales ALSFRS-R' (motor/respiratory components) and PSQI' (sleep efficiency/ daytime dysfunction), which more correlated with each other. Mediation analysis of these subscales revealed that depressive symptoms accounted for 36.3% of the indirect effect between ALSFRS-R' and PSQI'.

DISCUSSION: Our cross-sectional exploratory study suggests that depression may partly mediate the relationship between motor dysfunction and poor sleep quality in patients with ALS. Although our mediation analysis suggested a potential association, further longitudinal cohort studies are needed to confirm these findings. The potential mediating role of depression underscores the need for an integrated clinical management approach addressing not only motor symptoms but psychological well-being as well.},
}

@article {pmid41599691,
year = {2026},
author = {Zhao, X and Zheng, Y and Cai, X and Yao, Y and Qin, D},
title = {The Expanding Role of Non-Coding RNAs in Neurodegenerative Diseases: From Biomarkers to Therapeutic Targets.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {1},
pages = {},
doi = {10.3390/ph19010092},
pmid = {41599691},
issn = {1424-8247},
support = {Y202248634//Zhejiang Provincial Department of Education Project/ ; Y202454271//Zhejiang Provincial Department of Education Project/ ; },
abstract = {Non-coding RNAs have emerged as central regulators of gene expression in neurodegenerative diseases, offering new opportunities for diagnosis and therapy. This review synthesizes current knowledge on microRNAs, long non-coding RNAs, and circular RNAs in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, emphasizing their roles in synaptic function, proteostasis, mitochondrial biology, and neuroinflammation. We evaluate evidence supporting non-coding RNAs as circulating and tissue-based biomarkers for early detection, disease monitoring, and patient stratification, and we compare analytical platforms and biofluid sources. Mechanistic insights reveal how non-coding RNAs modulate pathogenic protein aggregation, neuronal excitability, immune cell crosstalk, and blood-brain barrier integrity. Translational efforts toward RNA-targeted interventions are reviewed, including antisense oligonucleotides, small interfering RNAs, miRNA mimics and inhibitors, circular RNA decoys, and extracellular vesicle-mediated delivery systems. We discuss pharmacological modulation, delivery challenges, safety concerns, and strategies to enhance specificity and CNS penetration. Finally, we outline emerging computational and multi-omics approaches to prioritize therapeutic targets and propose a roadmap for advancing non-coding RNA research from preclinical models to clinical trials. Addressing biological heterogeneity and delivery barriers will be pivotal to realizing the diagnostic and therapeutic promise of the non-coding transcriptome in neurodegenerative disease. Collaboration across disciplines and rigorous clinical validation are urgently needed.},
}

@article {pmid41599368,
year = {2026},
author = {Niziński, P and Szalast, K and Makuch-Kocka, A and Paruch-Nosek, K and Ciechanowska, M and Plech, T},
title = {Experimental Models and Translational Strategies in Neuroprotective Drug Development with Emphasis on Alzheimer's Disease.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {2},
pages = {},
doi = {10.3390/molecules31020320},
pmid = {41599368},
issn = {1420-3049},
support = {2022/47/O/NZ7/00155//National Science Centre/ ; },
mesh = {Humans ; *Alzheimer Disease/drug therapy/metabolism/pathology ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Drug Development ; Animals ; *Translational Research, Biomedical ; Disease Models, Animal ; Induced Pluripotent Stem Cells ; },
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are becoming more prevalent and still lack effective disease-modifying therapies (DMTs). However, translational efficiency remains critically low. For example, a ClinicalTrials.gov analysis of AD programs (2002-2012) estimated ~99.6% attrition, while PD programs (1999-2019) achieved an overall success rate of ~14.9%. In vitro platforms are assessed, ranging from immortalized neuronal lines and primary cultures to human-induced pluripotent stem cell (iPSC)-derived neurons/glia, neuron-glia co-cultures (including neuroinflammation paradigms), 3D spheroids, organoids, and blood-brain barrier (BBB)-on-chip systems. Complementary in vivo toxin, pharmacological, and genetic models are discussed for systems-level validation and central nervous system (CNS) exposure realism. The therapeutic synthesis focuses on AD, covering symptomatic drugs, anti-amyloid immunotherapies, tau-directed approaches, and repurposed drug classes that target metabolism, neuroinflammation, and network dysfunction. This review links experimental models to translational decision-making, focusing primarily on AD and providing a brief comparative context from other NDDs. It also covers emerging targeted protein degradation (PROTACs). Key priorities include neuroimmune/neurovascular human models, biomarker-anchored adaptive trials, mechanism-guided combination DMTs, and CNS PK/PD-driven development for brain-directed degraders.},
}

Humans
*Alzheimer Disease/drug therapy/metabolism/pathology
*Neuroprotective Agents/pharmacology/therapeutic use
*Drug Development
Animals
*Translational Research, Biomedical
Disease Models, Animal
Induced Pluripotent Stem Cells

@article {pmid41599225,
year = {2026},
author = {Bernatoniene, J and Kopustinskiene, DM and Casale, R and Medoro, A and Davinelli, S and Saso, L and Petrikonis, K},
title = {Nrf2 Modulation by Natural Compounds in Aging, Neurodegeneration, and Neuropathic Pain.},
journal = {Pharmaceutics},
volume = {18},
number = {1},
pages = {},
doi = {10.3390/pharmaceutics18010118},
pmid = {41599225},
issn = {1999-4923},
support = {S-A-UEI-23-7//Research Council of Lithuania (LMTLT)/ ; },
abstract = {This review summarizes the role of nuclear factor erythroid 2-related factor 2 (Nrf2) as a common link between aging, neurodegeneration, and neuropathic pain. Aging is characterized by oxidative stress and constant inflammation, which coincides with reduced Nrf2 activity and weaker antioxidant responses, increasing vulnerability to diseases. In neurodegenerative disorders-including Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis-evidence indicates that impaired Nrf2 signaling contributes to oxidative damage, neuroinflammation, and mitochondrial dysfunction. Furthermore, in neuropathic pain, similar mechanisms are involved, and Nrf2 could play a role as a potential analgesic target because of its role in regulating cellular defense pathways. We also review natural Nrf2 modulators (e.g., flavonoids, other polyphenols, terpenoids, alkaloids), discussing their benefits alongside common translational limitations such as poor solubility, low oral bioavailability, rapid metabolism, and potential safety issues, including possible pro-oxidant effects and chemoresistance. We also outline future directions that should prioritize improving delivery systems, addressing NRF2/KEAP1 gene variations, evaluating combinations with standard therapies, exploring preventive applications, and defining dosing, treatment duration, and long-term safety. Overall, current evidence indicates that Nrf2 modulation is a practical, cross-cutting approach relevant to healthy aging and disease management.},
}

@article {pmid41599185,
year = {2026},
author = {Benech, H and Flament, V and Lhotellier, C and Roucairol, C and Joudinaud, T},
title = {New Insights into Drug Development via the Nose-to-Brain Pathway: Exemplification Through Dodecyl Creatine Ester for Neuronal Disorders.},
journal = {Pharmaceutics},
volume = {18},
number = {1},
pages = {},
doi = {10.3390/pharmaceutics18010080},
pmid = {41599185},
issn = {1999-4923},
abstract = {Brain disorders remain a major global health challenge, highlighting the urgent need for innovative therapeutic strategies and efficient drug-delivery approaches. Among alternative routes, intranasal administration has garnered significant interest over recent decades, not only for its systemic delivery but also for its unique ability to bypass the bloodstream and the blood-brain barrier via the Nose-to-Brain (NtB) pathway. While numerous reviews have explored the opportunities and challenges of this route, industrial considerations-critical for successful clinical implementation and commercial development-remain insufficiently addressed. This review provides a comprehensive and critical assessment of the NtB pathway from a drug development and chemistry, manufacturing, and controls perspective, addressing key constraints in pre-clinical-clinical extrapolation, formulation design, device selection, dose feasibility, chronic safety, and regulatory requirements. We also discuss recent advances in neuronal targeting mechanisms, also with a focus on the role of trigeminal nerves. Dodecyl creatine ester (DCE), a highly unstable in plasma creatine prodrug developed by Ceres Brain Therapeutics, is presented as an illustrative case study. Delivered as a nasal spray, DCE enables direct neuronal delivery, exemplifying the potential of the NtB pathway for disorders characterized by neuronal energy deficiency, including creatine transporter deficiency and mitochondrial dysfunction. Overall, the NtB pathway-or, more precisely, the "Nose-to-Neurons" pathway-offers distinct advantages for unstable molecules and metabolic supplementation, particularly in neuron-centric diseases. Its successful implementation will depend on rational molecule design, optimized nasal formulations, appropriate devices, and early integration of industrial constraints to ensure feasibility, scalability, and safety for long-term treatment.},
}

@article {pmid41598508,
year = {2026},
author = {Torikai, T and Ohara, H and Takeuchi, J and Yokoi, T and Itoh, Y and Koto, T and Shiraishi, A and Inoue, M},
title = {Surgical Outcomes and Differences in Values of Ocular Parameters Following Vitrectomy for Macular Hole over a 10-Year Period.},
journal = {Journal of clinical medicine},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/jcm15020570},
pmid = {41598508},
issn = {2077-0383},
abstract = {Background/Objectives: We aimed to compare the surgical outcomes of macular hole (MH) cases and evaluate how the axial length (AL) affected the outcomes. Methods: Six hundred and sixty-three eyes with MHs that underwent vitrectomy over the past 10 years were reviewed. The changes in AL were compared to those of 1948 eyes with idiopathic epiretinal membranes (ERMs) operated on during the same period. The MH cases for the 5 years from 2014 to 2018 were designated as the MH2014 group, and those from 2019 to 2023 as the MH2019 group. The ERM cases were divided similarly into the ERM2014 and ERM2019 groups. The clinical characteristics of the cases and surgical outcomes were compared. Results: The MH diameter, closure rate, and baseline and postoperative visual acuity were not significantly different. The use of the inverted internal limiting membrane flap technique was significantly higher in the MH2019 group (58%) than in the MH2014 group (24%, p < 0.001). The mean AL was significantly longer in the MH2019 group (25.2 ± 2.4 mm) than in the MH2014 group (24.6 ± 2.1 mm, p = 0.004). The incidence of myopic MHs with AL ≥ 26 mm and AL ≥ 30 mm was higher in the MH2019 group (30.9%, p = 0.008, 6.4%, p = 0.017, respectively). There was a significant trend for longer ALs over 10 years in the MH group (p = 0.002), but not in the ERM group. Conclusions: The increased AL and the rising proportion of eyes with myopic MHs indicate that the patient profile of eyes with MHs has changed over the past decade.},
}

@article {pmid41596533,
year = {2026},
author = {Bogus, K and Marchesi, N and Campagnoli, LIM and Pascale, A and Pałasz, A},
title = {Glial Cells as Key Mediators in the Pathophysiology of Neurodegenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {27},
number = {2},
pages = {},
doi = {10.3390/ijms27020884},
pmid = {41596533},
issn = {1422-0067},
mesh = {Humans ; *Neurodegenerative Diseases/pathology/metabolism/physiopathology ; *Neuroglia/metabolism/pathology ; Animals ; Microglia/metabolism/pathology ; Astrocytes/metabolism/pathology ; },
abstract = {Neurodegenerative disorders are characterized by progressive neuronal loss and dysfunction, yet increasing evidence indicates that glial cells are central mediators of both disease initiation and progression. Astrocytes, microglia, and oligodendrocyte lineage cells modulate neuronal survival by regulating neuroinflammation, metabolic support, synaptic maintenance, and proteostasis. However, dysregulated glial responses, including chronic microglial activation, impaired phagocytosis, altered cytokine production, and mitochondrial dysfunction, contribute to persistent inflammation and structural degeneration observed across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and multiple sclerosis. Recent advances in single-cell and spatial omics have revealed extensive glial heterogeneity and dynamic shifts between neuroprotective and neurotoxic phenotypes, emphasizing the context-dependent nature of glial activity. This review summarizes current knowledge regarding the multifaceted involvement of glial cells in neurodegenerative disorders.},
}

Humans
*Neurodegenerative Diseases/pathology/metabolism/physiopathology
*Neuroglia/metabolism/pathology
Animals
Microglia/metabolism/pathology
Astrocytes/metabolism/pathology

@article {pmid41596266,
year = {2026},
author = {Ryu, IS and Ha, DI and Jung, YJ and Lee, HJ and Kim, I and Lim, YN and Min, HS and Kim, SH and Yoon, I and Cho, HJ and Ryu, JH},
title = {Modulation of the miR-485-3p/PGC-1α Pathway by ASO-Loaded Nanoparticles Attenuates ALS Pathogenesis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {2},
pages = {},
doi = {10.3390/ijms27020615},
pmid = {41596266},
issn = {1422-0067},
support = {RS-2023-00283779//Ministry of SMEs and Startups/ ; },
mesh = {*MicroRNAs/genetics/metabolism ; Animals ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/drug therapy ; *Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism/genetics ; *Nanoparticles/chemistry/administration & dosage ; Mice ; Mice, Transgenic ; Humans ; *Oligonucleotides, Antisense/pharmacology/administration & dosage/genetics ; Superoxide Dismutase-1/genetics/metabolism ; Spinal Cord/metabolism/pathology/drug effects ; Disease Models, Animal ; Signal Transduction/drug effects ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration with limited treatment options. In this study, we investigated the pathological role of microRNA-485-3p (miR-485-3p) in ALS, particularly its regulation of PGC-1α, a transcriptional coactivator essential for mitochondrial function and neuroprotection. We also evaluated the therapeutic potential of BMD-001S, a nanoparticle-based formulation encapsulating an antisense oligonucleotide targeting miR-485-3p. Our results demonstrated that miR-485-3p expression was significantly elevated in both SOD1[G93A]-expressing HMC3 microglial cells and in the spinal cords of SOD1[G93A] transgenic mice at late disease stages, implicating its contribution to ALS pathogenesis. Intravenous administration of BMD-001S effectively reduced miR-485-3p levels and restored PGC-1α mRNA and PGC-1α protein expression in the spinal cord. These molecular changes were associated with notable therapeutic outcomes, including reduced SOD1 protein aggregation, decreased neuroinflammation, and lower neurofilament light chain concentrations in cerebrospinal fluid. Moreover, BMD-001S treatment was associated with improvements in electrophysiological parameters and preservation of neuromuscular junction integrity during the observation period in SOD1[G93A] transgenic mice. Taken together, these findings suggest that miR-485-3p/PGC-1α pathway is a promising therapeutic target in ALS and support the potential of BMD-001S as a novel treatment strategy for the disease.},
}

*MicroRNAs/genetics/metabolism
Animals
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/drug therapy
*Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism/genetics
*Nanoparticles/chemistry/administration & dosage
Mice
Mice, Transgenic
Humans
*Oligonucleotides, Antisense/pharmacology/administration & dosage/genetics
Superoxide Dismutase-1/genetics/metabolism
Spinal Cord/metabolism/pathology/drug effects
Disease Models, Animal
Signal Transduction/drug effects

@article {pmid41596063,
year = {2025},
author = {Herbert, A},
title = {G-Quadruplexes Abet Neuronal Burnout in ALS and FTD.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/antiox15010005},
pmid = {41596063},
issn = {2076-3921},
abstract = {Expansion of d(GGGGC)n repeat in the C9ORF72 gene is causal for Amyotrophic Lateral Sclerosis (ALS) and Frontal Temporal Dementia (FTD). Proposed mechanisms include Repeat-Associated Non-AUG translation or the formation of G-quadruplexes (GQ) that disrupt translation, induce protein aggregation, sequester RNA processing factors, or alter RNA editing. Here, I show, using AlphaFold V3 (AF3) modeling, that the TAR DNA-binding protein (TDP-43) docks to a complex of GQ and hemin. TDP-43 methionines lie over hemin and likely squelch the generation of superoxide by the porphyrin-bound Fe. These TDP-43 methionines are frequently altered in ALS patients. Tau protein, a variant of which causes ALS, also binds to GQ and heme and positions methionines to detoxify peroxides. Full-length Tau, which is often considered prone to aggregation and a prion-like disease agent, can bind to an array composed of multiple GQs as a fully folded protein. In ALS and FTD, loss-of-function variants cause an uncompensated surplus of superoxide, which sparks neuronal cell death. In Alzheimer's Disease (AD) patients, GQ and heme complexes bound by β-amyloid 42 (Aβ4) are also likely to generate superoxides. Collectively, these neuropathologies have proven difficult to treat. The current synthesis provides a framework for designing future therapeutics.},
}

@article {pmid41595662,
year = {2026},
author = {Stoian, II and Nistor, D and Levai, MC and Popa, DI and Popescu, R},
title = {Directional Modulation of the Integrated Stress Response in Neurodegeneration: A Systematic Review of eIF2B Activators, PERK-Pathway Agents, and ISR Prolongers.},
journal = {Biomedicines},
volume = {14},
number = {1},
pages = {},
doi = {10.3390/biomedicines14010126},
pmid = {41595662},
issn = {2227-9059},
abstract = {Background and Objectives: The integrated stress response (ISR) is a convergent node in neurodegeneration. We systematically mapped open-access mammalian in vivo evidence for synthetic ISR modulators, comparing efficacy signals, biomarker engagement, and safety across mechanisms and disease classes. Methods: Following PRISMA 2020, we searched PubMed (MEDLINE), Embase, and Scopus from inception to 22 September 2025. Inclusion required mammalian neurodegeneration models; synthetic ISR modulators (eIF2B activators, PERK inhibitors or activators, GADD34-PP1 ISR prolongers); prespecified outcomes; and full open access. Extracted data included model, dose and route, outcomes, translational biomarkers (ATF4, phosphorylated eIF2α), and safety. Results: Twelve studies met the criteria across tauopathies and Alzheimer's disease (n = 5), prion disease (n = 1), amyotrophic lateral sclerosis and Huntington's disease (n = 3), hereditary neuropathies (n = 2), demyelination (n = 1), and aging (n = 1). Among interpretable in vivo entries, 10 of 11 reported benefit in at least one domain. By class, eIF2B activation with ISRIB was positive in three of four studies, with one null Alzheimer's hAPP-J20 study; PERK inhibition was positive in all three studies; ISR prolongation with Sephin1 or IFB-088 was positive in both studies; and PERK activation was positive in both studies. Typical regimens included ISRIB 0.1-2.5 mg per kg given intraperitoneally (often two to three doses) with reduced ATF4 and phosphorylated eIF2α; oral GSK2606414 50 mg per kg twice daily for six to seven weeks, achieving brain-level exposures; continuous MK-28 delivery at approximately 1 mg per kg; and oral IFB-088 or Sephin1 given over several weeks. Safety was mechanism-linked: systemic PERK inhibition produced pancreatic and other exocrine toxicities at higher exposures, whereas ISRIB and ISR-prolonging agents were generally well-tolerated in the included reports. Conclusions: Directional ISR control yields consistent, context-dependent improvements in behavior, structure, or survival, with biomarker evidence of target engagement. Mechanism matching (down-tuning versus prolonging the ISR) and exposure-driven safety management are central for translation.},
}

@article {pmid41594924,
year = {2026},
author = {Bao, Y and Miao, G and He, N and Bao, X and Shi, Z and Hu, C and Liu, X and Wang, B and Sun, C},
title = {Melatonin as a Guardian of Mitochondria: Mechanisms and Therapeutic Potential in Neurodegenerative Diseases.},
journal = {Biology},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/biology15020189},
pmid = {41594924},
issn = {2079-7737},
abstract = {Mitochondrial dysfunction is a key early pathological process in neurodegenerative diseases (NDs), leading to oxidative stress, impaired energy metabolism, and neuronal apoptosis prior to the onset of clinical symptoms. Although mitochondria represent important therapeutic targets, effective interventions targeting mitochondrial function remain limited. This review summarizes current evidence regarding the mechanisms by which melatonin protects mitochondria and evaluates its therapeutic relevance, with a primary focus on Alzheimer's disease, Parkinson's disease, and Huntington's disease-the major protagonists of NDs-while briefly covering other NDs such as amyotrophic lateral sclerosis, multiple sclerosis, and prion diseases. Melatonin selectively accumulates in neuronal mitochondria and exerts neuroprotection through multiple pathways: (1) direct scavenging of reactive oxygen species (ROS); (2) transcriptional activation of antioxidant defenses via the SIRT3 and Nrf2 pathways; (3) regulation of mitochondrial dynamics through DRP1 and OPA1; and (4) promotion of PINK1- and Parkin-mediated mitophagy. Additionally, melatonin exhibits context-dependent pleiotropy: under conditions of mild mitochondrial stress, it restores mitochondrial homeostasis; under conditions of severe mitochondrial damage, it promotes pro-survival autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby conferring stage-specific therapeutic advantages. Overall, melatonin offers a sophisticated mitochondria-targeting strategy for the treatment of NDs. However, successful clinical translation requires clarification of receptor-dependent signaling pathways, development of standardized dosing strategies, and validation in large-scale randomized controlled trials.},
}

@article {pmid41594611,
year = {2026},
author = {Dong, C and Lv, D and Dong, Y and Zhang, Z and Li, Q and Chen, Z},
title = {Advances in Cardiolipin Analysis: Applications in Central Nervous System Disorders and Nutrition Interventions.},
journal = {Biomolecules},
volume = {16},
number = {1},
pages = {},
doi = {10.3390/biom16010071},
pmid = {41594611},
issn = {2218-273X},
support = {2022CXPT037//the Key R&D Program of Shandong Province, China/ ; 5501290015//the Advanced Researcher Fund of Jiangsu University/ ; 202510299087//National Training Program of Innovation and Entrepreneurship for Undergraduates/ ; },
mesh = {*Cardiolipins/metabolism/analysis ; Humans ; *Central Nervous System Diseases/metabolism/diet therapy ; Animals ; Mitochondria/metabolism ; },
abstract = {Cardiolipin (CL), a unique dimeric phospholipid predominantly enriched in the inner mitochondrial membrane, is a crucial determinant of mitochondrial structure and function. Its content, fatty acyl composition, and oxidation state are associated with mitochondrial bioenergetics, dynamics, and cellular signaling. Disruptions in CL metabolism are increasingly implicated in the pathogenesis of various central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy, and traumatic brain injury. This narrative review summarizes recent advances in the analytical techniques employed for CL analysis. The principles and applications of mass spectrometry-based platforms, nuclear magnetic resonance, Fourier-transform infrared spectroscopy, atomic force microscopy-infrared spectroscopy, and fluorescent probes were discussed, with an emphasis on their strengths in revealing the structure, composition, dynamics, and spatial distribution of CL. Furthermore, the evidence of CL abnormalities in various CNS disorders was assessed, often showing decreased CL levels, loss of polyunsaturated species, and increased oxidation associated with mitochondrial dysfunction and neuronal apoptosis. Furthermore, the nutritional interventions for CL modulation were discussed, such as polyunsaturated fatty acids, polyphenols, carotenoids, retinoids, alkaloids, and triterpenoids, which summarize their potential health-beneficial effects in remodeling the CL acyl chain, preventing oxidation, and regulating mitochondrial homeostasis. Overall, this review provided insight into integrating CL analysis and dietary modulation in understanding CL-related pathologies in CNS disorders.},
}

*Cardiolipins/metabolism/analysis
Humans
*Central Nervous System Diseases/metabolism/diet therapy
Animals
Mitochondria/metabolism

@article {pmid41593859,
year = {2026},
author = {Pathak, K and Kumari, T and Aggarwal, L and Singh, V},
title = {Preventive dietary and lifestyle strategies for neurodegenerative diseases: a comprehensive review.},
journal = {Nutritional neuroscience},
volume = {},
number = {},
pages = {1-26},
doi = {10.1080/1028415X.2026.2615456},
pmid = {41593859},
issn = {1476-8305},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis, are rising sharply across the globe. These incurable and progressive conditions lead to severe cognitive and motor impairments, diminish the quality of life, and place a substantial burden on healthcare systems. In response to this growing challenge, the present review offers an integrative and forward-thinking perspective focused on modifiable daily habits that have the potential to preserve brain health and reduce the risk of neurodegeneration. Mounting evidence reveals that everyday lifestyle choices, including food habits, physical activity, sleep, and stress, profoundly shape long-term cognitive outcomes. Neuroprotective diets such as the Mediterranean and ketogenic diets reduce oxidative stress, enhance mitochondrial efficiency, and promote neurogenesis, whereas the Western diet accelerates cognitive decline. Intermittent fasting and caloric restriction trigger autophagy and ketone production, offering metabolic resilience. Functional foods such as berries, walnuts, and leafy greens combat inflammation and oxidative damage. Physical activity and resistance training boost synaptic plasticity and neurotransmitter balance. In addition, high-quality sleep and effective stress control help preserve neuronal integrity and lower neuroinflammatory markers. By integrating insights from neuroscience, nutrition, and behavioral medicine, this review highlights how multiple modifiable factors, when adopted consistently, can work in synergy to preserve cognitive health, delay disease onset, and reduce progression.},
}

@article {pmid41593729,
year = {2026},
author = {Nilsen, P and Kirk, JW and Gunnarsson, KU and Thomas, K},
title = {Matters arising: a critique of "Nuancing the continuum from ideal to real-world implementation" by Eldh et al. 2025.},
journal = {Implementation science communications},
volume = {7},
number = {1},
pages = {12},
pmid = {41593729},
issn = {2662-2211},
abstract = {This critique responds to Eldh et al.'s (Implement Sci Commun 6:113, 2025) commentary on Nilsen et al.'s proposal to distinguish between implementation efficacy and effectiveness along an ideal-to-real-world continuum. While acknowledging the constructive intent of Eldh et al.'s reflections, we clarify that our framework was never intended as a simplistic, one-dimensional model but as a pragmatic heuristic to enhance design transparency. Eldh et al.'s proposed two-axis alternative is conceptually overlapping, as both axes reflect contextual variation rather than independent constructs. Our adaptation of the PRECIS framework - long validated in clinical and health services research - already incorporates multidimensional nuance through distinct domains. We emphasize that the "ideal" end of the continuum denotes highly supported conditions, not normative perfection. Moreover, the proposed "Implementation PRECIS" tool is intended to stimulate integration of contextual transparency and economic evaluation within implementation research. While we concur with Eldh et al.'s emphasis on facilitation, co-production, and contextual complexity, their critique ultimately reinforces our core premise: that explicitly positioning studies along an efficacy-effectiveness spectrum strengthens interpretability, transparency, and real-world relevance in implementation science.},
}

@article {pmid41593242,
year = {2026},
author = {Hobson, R and Levy, SHS and Singal, CMS and Flaherty, D and Xiao, H and Ciener, B and Reddy, H and Zabinyakov, N and Kim, CY and Teich, AF and Shneider, NA and Bradshaw, EM and Elyaman, W},
title = {Clonal CD8[+] T cells populate the leptomeninges and coordinate with immune cells in human degenerative brain diseases.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {41593242},
issn = {1529-2916},
support = {PF-IMP-870699//Parkinson's Foundation (Parkinson's Foundation, Inc.)/ ; },
abstract = {Meningeal immune cells monitor the central nervous system (CNS) and influence neuroinflammation in mice, but the human leptomeningeal immune landscape and the changes that occur in this immunological niche in neurodegeneration remain underexplored. Here we performed single-cell RNA and T cell receptor (TCR) sequencing of 99,625 high-quality immune cells from 57 leptomeninges and brain samples from donors with Alzheimer's disease (AD), amyotrophic lateral sclerosis and Parkinson's disease and found that although the leptomeninges are home to highly clonally expanded CD8 tissue-resident memory (TRM) T cells, the maximal level of clonal expansion was decreased in AD in comparison to non-neurodegenerative controls. Intra-patient paired tissue analysis further revealed that brain and leptomeningeal TCR repertoires share significant similarities, but tissue-specific clones emerge in AD. Finally, in AD, the degree of CD8 TRM clonal expansion was positively correlated with microglial TGFB2, suggesting that brain and leptomeningeal immune cells coordinate their activities in AD. In addition to identifying key inflammatory dynamics in the human degenerating CNS, this study establishes a foundational resource for future studies that could inform treatment for AD and other neuroinflammatory diseases.},
}

@article {pmid41592787,
year = {2026},
author = {Mammone, RM and Willis, E and Ruivo, P and Finesso, GE and Cox, A and Assenmacher, CA and Radaelli, E and Piersigilli, A and Miranda, IC},
title = {Pathology associated with human CAR T cell administration in NOD.Cg-Prkdc[scid]Il2rg[tm1Wjl]/SzJ (NSG) mice: A retrospective analysis.},
journal = {Veterinary pathology},
volume = {},
number = {},
pages = {3009858251409216},
doi = {10.1177/03009858251409216},
pmid = {41592787},
issn = {1544-2217},
abstract = {Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment for neoplasia and autoimmune diseases. Immunocompromised mice are a common model to test the efficacy and safety of CAR T cells of human origin. Preclinical toxicity associated with human CAR T-cell products encompasses a spectrum of morphologic changes, with currently limited documentation in the scientific literature. The purpose of this retrospective study was to characterize the histopathologic features associated with human CAR T-cell administration in immunodeficient NOD.Cg-Prkdc[scid] Il2rg[tm1Wjl]/SzJ (NSG) mice (n = 392) submitted to 3 different academic institutions in the United States between 2017 and 2024. Lesions were categorized into xenogeneic graft-versus-host disease (xGvHD) (n = 287), aberrant proliferation of human T cells (n = 188), vascular pathologies (n = 66), on-target/off-tumor (OTOT) toxicity (n = 44), immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) in mice previously humanized with human CD34+ hematopoietic stem cells (HSCs) (n = 21), and acute lysis syndrome (ALS) (n = 5). This study provides veterinary pathologists with descriptive guidance on the pathology associated with human CAR T-cell therapy in immunodeficient mice. Additional molecular data and detailed information related to each construct are necessary to further investigate the translatability of such liabilities to the clinical setting.},
}

@article {pmid41592170,
year = {2026},
author = {Allen, MD and Diab, V and Lezaic, N and Binet, M and Gentil, BJ and Blanchard, O and Genge, A and Massie, R},
title = {The genetics of autosomal recessive ALS: a review of the common forms and their phenotypes.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2026.2615110},
pmid = {41592170},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of upper and lower motor neurons. Most forms of ALS associated with a suspected causal variant are inherited in an autosomal dominant manner. However, there is an important subset of autosomal recessive (AR) variants, often associated with early-onset or atypical clinical features. Advances in genetic sequencing have led to increased recognition of AR ALS. In this review, we focus on four key confirmed AR ALS-associated genes, which appear to be most common-ALS2, SPG11, OPTN, and the D90A variant of SOD1-reviewing their pathophysiology and unique clinical manifestations. We also highlight very rare AR mutations implicated in ALS, including SYNE1, ATP13A2, and FUS, and some associated with overlap syndromes or debated pathogenicity including SIGMAR1, ERLIN1, and ERLIN2. These genes are involved in an array of processes including axonal transport, endosomal trafficking, oxidative stress response, and autophagy, suggesting distinct mechanisms of motor neuron degeneration. Some forms of AR ALS more frequently present with juvenile onset and slower progression, but other genes are associated with broader phenotypic spectra. This includes overlap with hereditary spastic paraplegia (HSP) and hereditary ataxias. Understanding these AR forms of ALS may enhance diagnostic precision, improve prognostication, and may pave the way for targeted gene therapies. This review underscores the emerging significance of AR inheritance in ALS and calls for deeper investigation into its molecular and clinical dimensions.},
}

@article {pmid41591873,
year = {2026},
author = {Henkenius, AJ and Banaag, A and Koehlmoos, TP},
title = {Comparison of Musculoskeletal Injury and Behavioral Health Diagnoses Among United States Army Active Duty Servicewomen in Ground Combat Versus Non-Ground Combat Specialties: An Update (2020-2023).},
journal = {Military medicine},
volume = {},
number = {},
pages = {},
doi = {10.1093/milmed/usaf642},
pmid = {41591873},
issn = {1930-613X},
support = {# HU0001-11-1-0023//Department of War, Defense Health Agency/ ; },
abstract = {INTRODUCTION: Historically, women in the U.S. Military have been prohibited from serving in ground combat occupational specialties (GCS) until the Secretary of Defense lifted the exclusion in January 2016, prompting studies into health outcomes for this new cohort. Phillips et al.(2016-2019) found that active duty servicewomen (ADSW) in GCS had lower odds of musculoskeletal injury (MSKI) and behavioral health (BH) diagnoses than peers in non-ground combat specialties (NGCS), likely because of a "healthy warrior" selection effect. With continued integration, cohort maturation, and factors such as the COVID-19 pandemic, this study updates MSKI and BH trends among ADSW from 2020 to 2023 and compares findings with the earlier cohort.

MATERIALS AND METHODS: This retrospective cross-sectional study used data from the Military Health System Data Repository (MDR), including all ADSW (n = 77,568) who served from January 1, 2020, to December 31, 2023. Women in the Guard, Reserve, or with pregnancy diagnoses during or in the year prior were excluded. Primary outcomes-MSKI and BH diagnoses-were identified via ICD-10 codes. Adjusted odds ratios (AORs) and 95% CIs were calculated using multivariable logistic regression, comparing GCS vs. NGCS ADSW while adjusting for age, race & ethnicity, rank, and BMI. Two-sample z-tests assessed differences from Phillips et al.s 2016 to 2019 estimates. This study received an exempt determination from the Institutional Review Board at the Uniformed Services University of the Health Sciences.

RESULTS: Of 77,568 ADSW, 5,024 (6.5%) served in GCS. Compared to NGCS, GCS women were younger (72.1% vs. 47.0% aged 18-23), more often enlisted (68.4% vs. 57.0%), and had lower obesity rates (8.4% vs. 12.6%), but higher rates of tobacco (7.7% vs. 7.6%), alcohol (7.9% vs. 6.7%), and substance use (2.5% vs. 1.9%). Adjusted analyses showed higher MSKI odds in GCS (AOR = 1.21, 95% CI: 1.13-1.30), a significant reversal from Phillips et al.(AOR = 0.86, 95% CI: 0.79-0.93; z = 6.01, P < .001). BH odds were lower in GCS (AOR = 0.83, 95% CI: 0.78-0.89), consistent with earlier findings (Phillips AOR = 0.87; 95% CI: 0.80-0.95).

CONCLUSIONS: The increase in MSKI odds for GCS women contrasts sharply with prior findings, suggesting the dissipation of the initial selection effect as more women enter and remain in combat roles. This shift may reflect greater exposure duration, cumulative physical demands, or pandemic-era fitness disruptions. The continued lower BH odds in GCS, despite higher substance use, may reflect resilience, unit cohesion, or underreporting tied to stigma. These findings highlight the need for targeted, female-specific injury prevention and confidential, destigmatized mental health support as the Army moves toward sex-neutral standards in combat fitness.},
}

@article {pmid41591303,
year = {2026},
author = {Zhang, Y and Liu, Y and Yao, Z and Lai, H and Chen, X and Wang, Z and Bao, Y and Li, T and Zhou, X and Chen, X and Yang, P},
title = {Alphaviral Capsid Proteins Inhibit Stress Granule Assembly via Competitive RNA Binding With G3BP1.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e17009},
doi = {10.1002/advs.202517009},
pmid = {41591303},
issn = {2198-3844},
support = {2025YFC3409700//National Key Research and Development Project of China/ ; 2025JCXK02//Interdisciplinary Research Project of Hangzhou Normal University/ ; 2025M772812//China Postdoctoral Science Foundation/ ; 32470733//National Natural Science Foundation of China/ ; 32170696//National Natural Science Foundation of China/ ; WU2022A002//Center of Synthetic Biology and Integrated Bioengineering of Westlake University/ ; },
abstract = {Viral infection is one of the conditions that induce stress granule (SG) formation, a cellular defense mechanism that exerts antiviral effects. To counteract this host response, viruses have evolved a broad spectrum of strategies to inhibit SG formation. However, the molecular mechanisms underlying SG inhibition remain poorly understood. The nucleocapsid proteins play a critical role in virus replication and host interaction. Here, using Semliki Forest Virus (SFV) as a model, we uncover the function of the alphavirus nucleocapsid in SG inhibition. This inhibitory function depends on oligomerization mediated by an N-terminal α-helix and with a positively charged intrinsically disordered region (IDR). We show that SFV capsid directly competes with G3BP1 for RNA binding, thereby disrupting G3BP1-RNA liquid-liquid phase separation (LLPS) in vitro and SG assembly in cells. This mechanism is conserved across the alphavirus family but is not shared by the nucleocapsid of SARS-CoV-2 or other endemic viruses examined. Notably, expression of a peptide from SFV capsid is sufficient to inhibit SG formation induced by Amyotrophic Lateral Sclerosis (ALS)-associated mutations, suggesting potential therapeutic applications. Our findings reveal mechanistic insight into SG modulation by the viral capsid protein and provide a possible bioengineering tool for probing SG dynamics in health and disease.},
}

@article {pmid41589772,
year = {2026},
author = {Zhu, J and Wen, T and Gao, N and Ma, M and Sun, X and Liu, F and Lin, P and Liu, S},
title = {Elevated Serum SIRT2 Is Associated With Rapid Progression and Cognitive Impairment in Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70162},
pmid = {41589772},
issn = {1097-4598},
support = {2020M672067//the China postdoctoral science foundation/ ; NSFC82001354//National Natural Science Foundation of China/ ; },
abstract = {INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) lacks reliable biomarkers to predict disease trajectories or guide therapeutic strategies. Sirtuin 2 (SIRT2), a NAD+-dependent deacetylase implicated in cytoskeletal destabilization and neuroinflammatory pathways in preclinical ALS models, represents a promising yet unvalidated biomarker candidate. We aimed to translate preclinical findings by validating SIRT2's role in ALS.

METHODS: A cross-sectional cohort study was conducted, comparing serum SIRT2 levels, measured via enzyme-linked immunosorbent assay (ELISA), between 182 ALS patients and 65 healthy controls. Clinical progression rates were derived from the ALS Functional Rating Scale-Revised (ALSFRS-R), and cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Edinburgh Cognitive and Behavioral ALS Screen (ECAS).

RESULTS: SIRT2 levels were significantly elevated in ALS patients versus controls, though diagnostic accuracy was modest (AUC = 0.620). Furthermore, SIRT2 levels showed a weak but significant positive correlation with disease progression rate (r = 0.182, p = 0.014) and inverse correlations with cognitive scores on both MMSE (r = -0.250, p = 0.032) and ECAS (r = -0.286, p = 0.031). Notably, SIRT2 demonstrated a limited but detectable ability to stratify patients into fast- and slow-progressing subgroups (AUC = 0.635).

DISCUSSION: These findings provide preliminary clinical evidence linking elevated serum SIRT2 to disease progression and cognitive impairment in ALS, thereby supporting its role in disease heterogeneity. This work lends clinical support to preclinical insights, suggesting SIRT2 may aid in prognosis prediction and may represent a potential therapeutic target, necessitating further studies.},
}

@article {pmid41589677,
year = {2026},
author = {Ozkan, A and Padmanabhan, HK and Shipman, SL and Azim, E and Kumar, P and Sadegh, C and Basak, AN and Macklis, JD},
title = {Directed differentiation of functional corticospinal-like neurons from endogenous SOX6+/NG2+ cortical progenitors.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
doi = {10.7554/eLife.100340},
pmid = {41589677},
issn = {2050-084X},
support = {NS045523/NS/NINDS NIH HHS/United States ; DP1 NS106665/NS/NINDS NIH HHS/United States ; NS049553/NS/NINDS NIH HHS/United States ; Regeneration Project Fellowship//McKnight Brain Research Institute/ ; },
mesh = {Animals ; *SOXD Transcription Factors/metabolism ; Mice ; *Cell Differentiation ; Basic Helix-Loop-Helix Proteins/metabolism ; Nerve Tissue Proteins/metabolism ; *Neurons/physiology/cytology ; *Neural Stem Cells/physiology ; *Proteoglycans/metabolism ; *Cerebral Cortex/cytology ; *Pyramidal Tracts/cytology ; },
abstract = {Corticospinal neurons (CSN) centrally degenerate in amyotrophic lateral sclerosis (ALS), along with spinal motor neurons, and loss of voluntary motor function in spinal cord injury (SCI) results from damage to CSN axons. For functional regeneration of specifically affected neuronal circuitry in vivo, or for optimally informative disease modeling and/or therapeutic screening in vitro, it is important to reproduce the type or subtype of neurons involved. No such appropriate in vitro models exist with which to investigate CSN selective vulnerability and degeneration in ALS, or to investigate routes to regeneration of CSN circuitry for ALS or SCI, critically limiting the relevance of much research. Here, we identify that the HMG-domain transcription factor Sox6 is expressed by a subset of NG2+ endogenous cortical progenitors in postnatal and adult cortex, and that Sox6 suppresses a latent neurogenic program by repressing proneural Neurog2 expression by progenitors. We FACS-purify these progenitors from postnatal mouse cortex and establish a culture system to investigate their potential for directed differentiation into CSN. We then employ a multi-component construct with complementary and differentiation-sharpening transcriptional controls (activating Neurog2, Fezf2, while antagonizing Olig2 with VP16:Olig2). We generate corticospinal-like neurons from SOX6+/NG2+ cortical progenitors and find that these neurons differentiate with remarkable fidelity compared with corticospinal neurons in vivo. They possess appropriate morphological, molecular, transcriptomic, and electrophysiological characteristics, without characteristics of the alternate intracortical or other neuronal subtypes. We identify that these critical specifics of differentiation are not reproduced by commonly employed Neurog2-driven differentiation. Neurons induced by Neurog2 instead exhibit aberrant multi-axon morphology and express molecular hallmarks of alternate cortical projection subtypes, often in mixed form. Together, this developmentally-based directed differentiation from cortical progenitors sets a precedent and foundation for in vitro mechanistic and therapeutic disease modeling, and toward regenerative neuronal repopulation and circuit repair.},
}

Animals
*SOXD Transcription Factors/metabolism
Mice
*Cell Differentiation
Basic Helix-Loop-Helix Proteins/metabolism
Nerve Tissue Proteins/metabolism
*Neurons/physiology/cytology
*Neural Stem Cells/physiology
*Proteoglycans/metabolism
*Cerebral Cortex/cytology
*Pyramidal Tracts/cytology

@article {pmid41588889,
year = {2026},
author = {Thakur, A and Chowdhury, KR and Kumar, A and Sharma, VV and Bhatia, R},
title = {Targeting Non-coding RNAs in Neurodegeneration: Advances in Therapeutic RNA Modalities and Next-Gen Delivery Technologies.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050421604251108045622},
pmid = {41588889},
issn = {1875-5828},
abstract = {Non-coding RNA (ncRNA)-based therapies represent an emerging and transformative approach in the treatment of neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)/Motor Neuron Disease (MND). This review explored the potential for targeting microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and exosomal RNAs, reinforced by promising results from clinical trials demonstrating their capacity to modulate disease pathways. The incorporation of cutting-edge computational methodologies, including RNA structure prediction and gene regulatory network analysis, has been at the forefront in enhancing the efficacy of ncRNA-based treatments. Moreover, chemical methods have improved RNA molecules' stability, accuracy, and directed delivery, enhancing their therapeutic effects. Moreover, cutting-edge RNA editing technologies like Clustered Regularly Interspaced Short Palindromic Repeats/CRISPRassociated protein 13 (CRISPR/Cas13) are advancing our ability to directly manipulate ncRNA expression, offering a powerful avenue for addressing the molecular origins of neurodegeneration. Despite these advances, challenges persist, particularly in ensuring the specificity, delivery efficiency, and long-term efficacy of these treatments. Nanotechnology provides innovative solutions to these obstacles, facilitating more efficient and precise RNA delivery, especially to neuronal tissue. In conclusion, ncRNA-based therapies, while still in nascent stages, represent a hopeful frontier in the fight against NDs. With ongoing research and technological advancements, these therapies could not only halt disease progression but also redefine the future of ND treatment, offering new avenues for patients' care and clinical success.},
}

@article {pmid41588556,
year = {2026},
author = {Wei, Z and Wang, R},
title = {Vanadium Nitride Decorated Graphene With Abundant Active Sites as Chemical Anchor of Polysulfides and Redox Catalysts in Aluminum Sulfur Batteries for Enhanced Performance.},
journal = {ChemSusChem},
volume = {19},
number = {2},
pages = {e202501845},
doi = {10.1002/cssc.202501845},
pmid = {41588556},
issn = {1864-564X},
abstract = {Aluminum-sulfur (Al-S) batteries are garnering significant interest as candidates for affordable energy storage systems due to their high theoretical capacity of 1672 mAh g[-1] and the cost-effectiveness of naturally abundant aluminum and sulfur. Nevertheless, challenges such as poor cyclic reversibility and limited practical capacity have resulted in only a few reversibly operating Al-S cells to date. In this study, we introduce an improved Al-S battery configuration by incorporating a novel VN@graphene catalyst into the sulfur cathode in Al-S battery applications. Comprehensive electrochemical tests and ex situ characterizations reveal that, during discharge, the catalyst effectively suppresses the polysulfide shuttle effect through strong adsorption, whereas during charging, it enhances sulfide redox kinetics. Consequently, the modified Al-S cell delivers an initial capacity of approximately 1354 mAh g[-1], maintaining around 507 mAh g[-1] after 200 cycles.},
}

@article {pmid41588209,
year = {2026},
author = {Hou, M and Xie, X and Hu, J and Rominger, A and Shi, K and Xiao, L and Tang, Y and Hu, S},
title = {Systemic brain-body metabolic coupling patterns in amyotrophic lateral sclerosis: a whole-body [[18]F] fluorodeoxyglucose PET/CT study across clinical phenotypes.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41588209},
issn = {1619-7089},
support = {81801740//National Natural Science Foundation of China/ ; 82272045//National Natural Science Foundation of China/ ; 2023LNJJ16//Clinical Research Foundation of the National Clinical Research Center for Geriatric Diseases(XIANGYA)/ ; 2022M723561//China Postdoctoral Science Foundation/ ; 2024JJ2094//Science Fund for Distinguished Young Scholars of Hunan Province/ ; grant number:Z2023004//National Key Clinical Specialty Scientific Research Project/ ; 2021RC4056//Science and Technology Innovation Program of Hunan Province/ ; CEIEC-2022-ZM02-0219//Key Program of Ministry of Industry and Information Technology of China/ ; },
}

@article {pmid41587040,
year = {2026},
author = {Tanaka, H and Black, LE and Forrest, SL and Danics, K and Sadia, N and Khodadadi, M and Tator, C and Smith, DH and Tartaglia, MC and Stewart, W and Kovacs, GG},
title = {Spinal Cord Tau and Protein Copathologies Associated With Chronic Traumatic Encephalopathy.},
journal = {JAMA neurology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaneurol.2025.5421},
pmid = {41587040},
issn = {2168-6157},
abstract = {IMPORTANCE: Exposure to repetitive head impacts (RHI) is associated with increased risk of a range of neurodegenerative diseases, including Alzheimer disease and amyotrophic lateral sclerosis. However, while the protein pathologies in the brains of individuals with the RHI-associated pathology of chronic traumatic encephalopathy (CTE) are well described, the spinal cord pathology in at-risk individuals remains poorly understood.

OBJECTIVE: To evaluate spinal cord pathologies associated with RHI exposure or CTE neuropathologic change (CTE-NC) in the brain.

This case-control study of a retrospective autopsy series (June 2019 to August 2025) was performed among autopsied individuals who served as RHI-exposed cases or controls in a multicenter brain bank collaboration. Data analysis was performed from January 2024 to November 2025.

EXPOSURES: RHI history and CTE-NC presence.

MAIN OUTCOMES AND MEASURES: Informant-reported clinical history as well as symptoms and immunohistochemistry for phosphorylated tau (p-tau), phosphorylated TAR DNA-binding protein 43 (p-TDP-43), α-synuclein, and amyloid-β (Aβ), as well as amyloid precursor protein and human leukocyte antigen DR.

RESULTS: Of 70 autopsied individuals (62 male, 8 female; mean [SD] age, 64.40 [13.94] years), 20 showed CTE-NC in the brain. All cases with CTE-NC exhibited spinal cord p-tau deposits, especially in cases aged 65 years or older with prior RHI (n = 14), often showing extensive spinal tau pathology as both neuronal (all 14 cases) and astrocytic (12 of 14 cases [86%]) p-tau deposits. Spinal p-tau pathology was associated with microglial activation and motor symptoms. Notably, among the individuals with CTE-NC and prior RHI who were aged 65 years or older, additional spinal protein pathologies were present, comprising p-TDP-43 inclusions (9 of 14 cases [64%]), Aβ deposits (13 of 14 cases [93%]), and α-synuclein deposits (7 of 14 cases [50%]), with all 4 of these pathologies present in 4 individuals (29%). In total, across all 20 CTE-NC cases, p-TDP-43 inclusions were confined to the spinal cord in 5 of the 10 individuals with spinal p-TDP-43 pathology. In contrast, among 50 individuals without CTE-NC, typically sparse p-tau deposits were seen in only 27 (54%). Among the 23 confirmed cases with a history of RHI, 16 (70%) exhibited CTE-NC, while 7 (30%) did not. Spinal tau pathology was more severe in those with CTE-NC; however, astrocytic tau pathology was also present in the group without CTE-NC, unlike in controls without RHI or CTE.

CONCLUSIONS AND RELEVANCE: This case-control study provides autopsy evidence of a high prevalence of complex spinal pathology in individuals with CTE-NC, supporting the concept of trauma-related encephalomyelopathy. The frequent co-occurrence of p-TDP-43, Aβ, and α-synuclein pathologies in individuals aged 65 years or older with CTE-NC suggests that cumulative trauma might contribute to widespread misfolded protein aggregation.},
}

@article {pmid41586932,
year = {2026},
author = {Ma, H and Liu, M and Yang, J and Li, J and He, A and Li, M and Guan, W and Shi, J and Teng, J},
title = {Lipid Metabolic Mediators Bridge Ischemic Heart Disease and Amyotrophic Lateral Sclerosis.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {396},
pmid = {41586932},
issn = {1559-1182},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics ; Humans ; *Lipid Metabolism/genetics ; *Myocardial Ischemia/metabolism/genetics/complications ; Mendelian Randomization Analysis ; MicroRNAs/metabolism/genetics ; Protein Interaction Maps ; },
abstract = {While epidemiological studies have linked cardiovascular disease (CVD) and amyotrophic lateral sclerosis (ALS), the causal pathways remain unclear. This study aims to clarify the causal relationship between CVD and ALS, with a focus on lipid metabolism as a potential mediator. We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between CVD and ALS. Furthermore, we utilized mediation MR, summary-data-based MR analysis (SMR), the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) pathway analysis, miRNA interaction prediction analysis, and protein-protein interaction (PPI) studies to validate the mediating effect of lipid metabolism on the risk of CVD and ALS onset, as well as to predict potential signaling pathways and mechanisms. The MR analysis revealed a significant association between CVD, particularly IHD, and an increased risk of ALS. Mediation analysis indicated that the level of sphingomyelin (d34:0) in serum may mediate the effect of IHD on ALS, along with the identification of seven additional types of plasma metabolites. Furthermore, KEGG and GO analyses highlighted lipid metabolism pathways, including "cholesterol metabolism" and the "phospholipid metabolic process." Additionally, miRNA interaction prediction analysis identified MFGE8 as a potential therapeutic target. Our study identifies IHD as a vascular risk factor for ALS, driven by lipid metabolic dysregulation. The identification of sphingomyelin (d34:0) and MFGE8 as key mediators in lipid metabolic dysregulation offers potential preventive and therapeutic strategies for CVD patients at elevated risk of ALS.},
}

*Amyotrophic Lateral Sclerosis/metabolism/genetics
Humans
*Lipid Metabolism/genetics
*Myocardial Ischemia/metabolism/genetics/complications
Mendelian Randomization Analysis
MicroRNAs/metabolism/genetics
Protein Interaction Maps

@article {pmid41586560,
year = {2026},
author = {Muñoz-Rugeles, L and Alvarez-Idaboy, JR and Espinosa Rincón, N and Mejía-Ospino, E},
title = {Chemical repair of oxidized aromatic amino acids by monohydroxylated 2-pyridones.},
journal = {The Journal of chemical physics},
volume = {164},
number = {4},
pages = {},
doi = {10.1063/5.0307155},
pmid = {41586560},
issn = {1089-7690},
mesh = {Oxidation-Reduction ; *Pyridones/chemistry ; Density Functional Theory ; *Amino Acids, Aromatic/chemistry ; Tryptophan/chemistry ; *Antioxidants/chemistry ; Kinetics ; Free Radicals/chemistry ; },
abstract = {The oxidative modification of tryptophan and tyrosine residues in proteins has been strongly associated with the onset and progression of neurodegenerative disorders, such as Alzheimer's disease and amyotrophic lateral sclerosis. Consequently, the identification of small molecules capable of repairing these oxidized residues is of considerable medicinal interest. In this study, the antioxidant activity of four hydroxy-2-pyridones against tyrosyl and tryptophanyl radicals was investigated in silico using density functional theory, with the aim of elucidating their structure-activity relationships at the molecular level. Thermochemical analyses were conducted to evaluate the most favorable repair pathways, focusing on formal hydrogen transfer (FHT) and single electron transfer (SET) processes. For exergonic reactions, kinetic parameters were determined within the quantum mechanics-based overall free radical scavenging activity (QM-ORSA) protocol, providing predictive data on radical-scavenging efficiency. The results indicate that three of the tested pyridones can repair the tyrosyl radical and that two of them react at rates comparable with the dityrosine formation, thereby competing with this deleterious pathway. In contrast, all four pyridones are able to reduce the tryptophanyl radical, although the calculated kinetics suggest that they may not efficiently suppress the Trp-Trp cross-linking in small peptides. Mechanistic analysis further revealed that FHT proceeds through proton-coupled electron transfer for tyrosyl radical repair, whereas tryptophanyl radical repair involves a proton-electron sequential transfer mechanism. These findings establish hydroxy-2-pyridones as promising scaffolds for the rational design of neuroprotective antioxidants and provide molecular insights that may guide the development of new therapeutic agents targeting oxidative stress.},
}

Oxidation-Reduction
*Pyridones/chemistry
Density Functional Theory
*Amino Acids, Aromatic/chemistry
Tryptophan/chemistry
*Antioxidants/chemistry
Kinetics
Free Radicals/chemistry

@article {pmid41586107,
year = {2025},
author = {Berthiaume, AA and Kleist, KN and Reda, SM and Setti, SE and Wu, W and Johnston, JL and Taylor, RW and Stein, LR and Church, KJ},
title = {ATH-1105 mitigates multiple pathologies in ALS models both alone and in combination with riluzole.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1582765},
pmid = {41586107},
issn = {1664-2295},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration, muscle atrophy, and paralysis. The complexity of ALS pathology, driven by factors such as TDP-43 pathology, excitotoxicity, and neuroinflammation, has hindered therapeutic development. While riluzole (an anti-excitotoxic agent) is the current standard treatment, additional therapeutics are needed to address the broad spectrum of ALS-related pathology. ATH-1105, a small-molecule positive modulator of hepatocyte growth factor (HGF) signaling, has shown promise in preclinical models of ALS. Given the multifactorial nature of ALS and the growing recognition that combination approaches may represent the best treatment options, we investigated the therapeutic potential of ATH-1105 in a TDP-43-driven mouse model of ALS, by comparing and combining it with the known efficacious treatment of riluzole. Additionally, we characterize the mechanism by which ATH-1105 induces neuroprotective effects, emphasizing its effects on TDP-43 pathology.

METHODS: In vivo, the impact of daily oral treatment with ATH-1105, alone and in combination with riluzole, was evaluated in Prp-TDP43[A315T] hemizygous transgenic ALS mice. In vitro, the impact of ATH-1105 on TDP-43-related pathology was assessed in rat primary spinal motor neurons subjected to glutamate toxicity. To demonstrate target engagement, the neuroprotective effects of ATH-1105 were assessed via siRNA-mediated knockdown of MET (HGF receptor).

RESULTS: In vivo, ATH-1105 significantly improved neuromuscular function and reduced body weight loss, neurodegeneration, inflammation, and TDP-43 phosphorylation. The combination of ATH-1105 with riluzole led to greater therapeutic effects than either treatment alone. In vitro, the neuroprotective effects of ATH-1105 were shown to be associated with MET activation in motor neurons, which was confirmed via siRNA-mediated knockdown of MET. In motor neurons subjected to glutamate toxicity, ATH-1105 reduced extranuclear and phosphorylated TDP-43, and increased GSK3β phosphorylation (inactivation), a kinase involved in TDP-43 pathology. Additionally, ATH-1105 reduced the abnormal increase in autophagic proteins following glutamate toxicity.

DISCUSSION: Our study underscores the therapeutic potential of ATH-1105 in treating ALS, both as a standalone treatment and in combination with riluzole. ATH-1105 demonstrates neuroprotective effects that slow neuromuscular deterioration in a relevant mouse model, aligning with the need to counteract the neurodegeneration central to ALS.},
}

@article {pmid41585784,
year = {2026},
author = {Jilani, SB and Ashok, N and Bomble, YJ and Guss, AM and Olson, DG},
title = {Engineering Clostridium thermocellum for production of 2,3-butanediol from cellulose.},
journal = {Metabolic engineering communications},
volume = {22},
number = {},
pages = {e00269},
pmid = {41585784},
issn = {2214-0301},
abstract = {Clostridium thermocellum is a promising host for consolidated bioprocessing due to its ability to directly ferment cellulose into fuels and chemicals. However, natural product formation in this organism is limited. Here, we report engineering C. thermocellum for the production of 2,3-butanediol (23BD), a valuable industrial chemical. We functionally expressed a thermophilic 23BD pathway in this organism resulting in a 23BD titer of 19.7 mM from cellulose, representing a metabolic yield of 24%. We used a cell-free systems biology approach to identify limiting steps in the 23BD pathway, revealing that exogenous 23BD dehydrogenase (BDH) activity was essential for production, while native acetolactate synthase (ALS) and acetolactate decarboxylase (ALDC) activities were present but limiting in the parent strain. This approach also revealed redox balance limitations. We demonstrated that this improved understanding of redox balance limitations could be used to increase 23BD titer in vivo, showing that adding acetate could be used to increase 23BD yield. This work establishes a foundation for developing C. thermocellum into a robust platform for 23BD production directly from cellulose and highlights the utility of cell-free systems for guiding metabolic engineering in non-model organisms.},
}

@article {pmid41585268,
year = {2025},
author = {Srivastav, J and Sharma, S},
title = {Viral and non-viral cellular therapies for neurodegeneration.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1718669},
pmid = {41585268},
issn = {2296-858X},
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive loss of neurons and still lack curative treatment options. In this review, we describe current and developing therapeutic strategies that include viral vector-based gene delivery, antisense oligonucleotide (ASO) and RNA interference methods, stem cell transplantation, and genome editing technologies. Adeno-associated viruses (AAVs) and lentiviruses have been used for gene delivery in preclinical and clinical studies, while ASOs are under development to reduce expression of pathogenic proteins such as tau, α-synuclein, and mutant huntingtin. Cellular therapies, including mesenchymal stem cell (MSC)-based paracrine support and transplantation of neurons derived from induced pluripotent stem cells (iPSCs), are being evaluated, particularly in PD and AD. We also discuss important gene targets such as APOE4, GBA1, SCNA, and MAPT, and how treatment strategies may differ between monogenic and polygenic forms of these disorders. Lastly, we highlight recent efforts focused on genes like TREM2, PINK1, and progranulin, and examine their role in the future development of gene- and cell-based interventions.},
}

@article {pmid41583923,
year = {2026},
author = {Gonzalez, M and Lato, TJ and Alonzo, EA and Park, S and Green, MT and Soto-Rodriguez, N and Shaw, BF},
title = {Does sod1 encode a molecular clock? Mutations that mimic asparagine deamidation inhibit heterodimerization with ALS-mutant SOD1.},
journal = {RSC chemical biology},
volume = {},
number = {},
pages = {},
pmid = {41583923},
issn = {2633-0679},
abstract = {The self-exchange of subunits by protein homodimers is a common protein-protein interaction in vivo. In heterozygous genetic disorders involving homodimeric gene products, both mutant and WT proteins can exchange subunits (heterodimerize). This form of heterodimerization can be analytically challenging to study. In this paper, we used capillary electrophoresis to investigate how deamidation of multiple asparagine residues (to aspartate) in homodimeric Cu, Zn superoxide dismutase-1 (SOD1) affected the rate and free energy of heterodimerization between WT and mutant SOD1 that cause amyotrophic lateral sclerosis (ALS). To model asparagine deamidation, Asn to Asp substitutions were introduced at five Asn residues predicted to undergo the most rapid deamidation in SOD1 (N26D, N131D, N139D, N65D, N19D). This model of penta-deamidated SOD1 did not heterodimerize with WT SOD1 or E100K SOD1 (linked to ALS). In contrast, the quad-variant N26D/N131D/N139D/N19D SOD1 did heterodimerize. These results suggest that the WT SOD1 protein has an intrinsic "timer" or "molecular clock" (as spontaneous Asn deamidation has been described) that effectively stops its heterodimerization after the SOD1 protein has existed in solution for ∼3 months.},
}

@article {pmid41583004,
year = {2025},
author = {Hu, Z and Wan, JJ and Yan, QQ and Fan, Y and Liu, J},
title = {Exploring rare coding variants in UK biobank: preliminary associations with motor neuron disease.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1735522},
pmid = {41583004},
issn = {1663-4365},
abstract = {INTRODUCTION: Previous studies have illuminated a significant genetic component in motor neuron disease (MND) pathogenesis, with several causative genes identified. However, a substantial proportion of MND cases remain genetically unexplained, particularly regarding the comprehensive contribution of rare, high-impact variants across the exome.

METHODS: Leveraging whole-exome sequencing data from nearly half a million UK Biobank participants, we systematically investigated the association between high-confidence protein-truncating variants (HC PTVs) and MND risk in a Caucasian subset. Our large-scale gene-based association analysis utilized REGENIE software and LOFTEE-defined HC PTVs.

RESULTS: We identified significant preliminary associations between HC PTVs in 14 genes and an increased risk of MND. Notably, while NEK1 has been previously implicated in ALS, the remaining 13 genes (BLVRB, KLHL32, RIMS2, DYDC2, DCBLD1, ANXA4, COMP, TRIM42, ANO4, NFX1, CFAP206, CKAP2L, and ANGPTL4) show preliminary associations as novel candidate loci for the disease. Functional enrichment analyses further indicated that these genes are significantly involved in critical biological pathways, including collagen-containing extracellular matrix organization and ciliary function. Furthermore, tissue specificity analysis highlighted a strong enrichment of these genes' expression in brain regions, with the hypothalamus showing the highest specificity.

DISCUSSION: These findings suggest a potential expansion of the known genetic landscape of MND, and highlight novel biological pathways implicated in its pathogenesis. This study underscores the power of large-scale population genetics in uncovering critical disease mechanisms and offers new avenues for mechanistic research and therapeutic development for MND, pending independent validation.},
}

@article {pmid41582654,
year = {2026},
author = {Long, C and Horty, LG},
title = {Synthesis of Florasulam Stable Isotopes to Enable Identification of Degradants by Mass Spectrometry for Re-registration Studies.},
journal = {Journal of labelled compounds & radiopharmaceuticals},
volume = {69},
number = {2},
pages = {e70005},
doi = {10.1002/jlcr.70005},
pmid = {41582654},
issn = {1099-1344},
mesh = {*Herbicides/chemical synthesis/chemistry ; Mass Spectrometry/methods ; *Pyrimidines/chemical synthesis/chemistry ; *Triazoles/chemical synthesis/chemistry ; Carbon Isotopes/chemistry ; Chemistry Techniques, Synthetic ; Nitrogen Isotopes/chemistry ; Isotope Labeling ; },
abstract = {Florasulam is a triazolopyrimidine herbicide that controls broadleaf and grass weeds in cereal crops and turf. It acts as an acetolactase synthase (ALS) inhibitor, blocking the synthesis of essential amino acids required for plant growth. Due to its potency, florasulam is effective at very low application rates making it cost-effective with reduced environmental off-target effects. As is common practice, florasulam has been subject to periodic reviews by regulatory agencies during re-registration requirements since its introduction into the market in 1998. The goal of these reviews is to ensure that the herbicide carries out its intended use without creating adverse side effects to humans and the environment. Since scientific methods are continually evolving and being developed, global regulatory agencies can require additional studies to address data gaps for pesticide renewals. During this re-registration process for florasulam, new environmental fate studies were conducted to meet new European Food Safety Authority (EFSA) guidelines. Consequently, florasulam-[triazole([13]C,[15]N2)] and florasulam-[phenyl([13]C6)] stable isotopes were synthesized to support the re-registration process.},
}

*Herbicides/chemical synthesis/chemistry
Mass Spectrometry/methods
*Pyrimidines/chemical synthesis/chemistry
*Triazoles/chemical synthesis/chemistry
Carbon Isotopes/chemistry
Chemistry Techniques, Synthetic
Nitrogen Isotopes/chemistry
Isotope Labeling

@article {pmid41582437,
year = {2026},
author = {Chen, X and Cao, Z and Liang, X and Zhao, T and Wang, Y},
title = {TRIM9 and TRIM26 Interact with UBQLN2[P497H] to Modulate Its Proteasomal Degradation.},
journal = {ACS chemical biology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschembio.5c00911},
pmid = {41582437},
issn = {1554-8937},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss. ALS-linked mutations in UBQLN2 promote protein aggregation and disrupt proteostasis, yet the mutation-specific protein interactomes and their functional relevance remain poorly defined. We employed APEX2 proximity labeling, together with affinity enrichment of biotinylated peptides and LC-MS/MS analysis, to profile the interactomes of wild-type UBQLN2 and two ALS-linked variants, UBQLN2[P497H] and UBQLN2[P497S]. We identified 785 unique biotinylated proteins, many of which exhibit augmented enrichment in the proximity proteomes of the two mutants over wild-type UBQLN2. Notably, the E3 ubiquitin ligases TRIM9 and TRIM26 were selectively enriched in the proximity proteome of UBQLN2[P497H], which we validated by coimmunoprecipitation followed by Western blot analysis. Fractionation analysis revealed coaccumulation of TRIM9 and TRIM26 with UBQLN2[P497H] in the insoluble fraction, consistent with its heightened aggregation propensity. Treatment of UBQLN2[P497H]-expressing cells with a proteasomal inhibitor led to elevated accumulation of a C-terminal UBQLN2 fragment that is absent in cells expressing wild-type UBQLN2 or its P497S mutant. Individual knockdown of TRIM9 and TRIM26 significantly increased the abundance of the fragment, establishing UBQLN2[P497H] as a substrate for TRIM9- and TRIM26-mediated ubiquitinylation and subsequent proteasomal degradation. These findings nominate TRIM9 and TRIM26 as specific interactors of UBQLN2[P497H] and as regulators of a previously underexplored C-terminal UBQLN2 fragment, suggesting that impaired clearance of this species may contribute to ALS pathogenesis.},
}

@article {pmid41581940,
year = {2026},
author = {Behera, P and Rangappa, N and Chandrashekar, M and Mishra, A and Chinnathambi, S and Mishra, M},
title = {The multifaceted role of antimicrobial peptides in neurodegeneration: Insights from Drosophila and beyond.},
journal = {Advances in protein chemistry and structural biology},
volume = {149},
number = {},
pages = {419-444},
doi = {10.1016/bs.apcsb.2025.08.003},
pmid = {41581940},
issn = {1876-1631},
mesh = {Animals ; Humans ; *Neurodegenerative Diseases/immunology/metabolism/pathology ; *Antimicrobial Peptides/metabolism/immunology ; *Drosophila ; Disease Models, Animal ; Immunity, Innate ; },
abstract = {Antimicrobial peptides (AMPs) are tiny proteins essential for innate immunity in various taxa, including mammals and insects. They provide defence against a wide range of pathogens, including bacteria, viruses, fungi, and parasites. Apart from their antimicrobial properties, new studies have revealed the roles of AMPs in brain ageing, neurodegeneration, and neuroinflammation. With an emphasis on their dysregulation in glial and neuronal tissues and their role in neuroinflammation, mitochondrial dysfunction, and neuronal loss, we reviewed the new function of AMPs beyond their antimicrobial activity. Findings from Drosophila models of Huntington's disease, Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Ataxia-telangiectasia show that immune pathways, like Toll and immune deficiency, drive persistent or ectopic AMP expression, which is similar to the inflammatory processes seen in human neurodegenerative diseases. Furthermore, the dual function of AMPs as mediators of sterile inflammation and protective immunological agents reveals a universal paradox. The translational relevance of these findings is further supported by comparisons with human AMPs, such as LL-37 and β-defensins. LL-37 and β-defensins levels were found to be increased in the cerebrospinal fluid of patients suffering from meningitis. LL-37 is released from neurons and activates glial cells, boosting the production of inflammatory cytokines and decreasing neuronal survival. This chapter redefines AMPs as not only sentinels of microbial defence but also as important participants in preserving or disturbing brain homeostasis by establishing them as a link between immunity and neurobiology.},
}

Animals
Humans
*Neurodegenerative Diseases/immunology/metabolism/pathology
*Antimicrobial Peptides/metabolism/immunology
*Drosophila
Disease Models, Animal
Immunity, Innate

@article {pmid41581503,
year = {2026},
author = {Hung, ST and Linares, GR and Chang, WH and Eoh, Y and Krishnan, G and Mendonca, S and Hong, S and Shi, Y and Santana, M and Kueth, C and Macklin-Isquierdo, S and Perry, S and Duhaime, S and Maios, C and Chang, J and Perez, J and Couto, A and Lai, J and Li, Y and Alworth, SV and Hendricks, E and Wang, Y and Zlokovic, BV and Dickman, DK and Parker, JA and Zarnescu, DC and Gao, FB and Ichida, JK},
title = {PIKFYVE inhibition mitigates disease in models of diverse forms of ALS.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2026.01.004},
pmid = {41581503},
issn = {1097-4172},
}

@article {pmid41581418,
year = {2026},
author = {Aphale, P and Dokania, S and Shekhar, H},
title = {Critique of Gammenthaler-Zaugg et al.'s Study on Point-of-Care Electroencephalography for Seizure Detection.},
journal = {Pediatric neurology},
volume = {176},
number = {},
pages = {124-125},
doi = {10.1016/j.pediatrneurol.2026.01.005},
pmid = {41581418},
issn = {1873-5150},
}

@article {pmid41581145,
year = {2026},
author = {McCourt, B and Lemr, K and Chakrabarti, S and Woidke, E and Ramaiah, S and Singh, V and Sangwan, N and Brown, JM and Cominelli, F and Rodriguez-Palacios, A and Burberry, A},
title = {C9orf72 in myeloid cells prevents an inflammatory response to microbial glycogen.},
journal = {Cell reports},
volume = {45},
number = {2},
pages = {116906},
doi = {10.1016/j.celrep.2025.116906},
pmid = {41581145},
issn = {2211-1247},
abstract = {Gut dysbiosis and neural inflammation occur in patients with amyotrophic lateral sclerosis (ALS), including those with a causal mutation in chromosome 9 open reading frame 72 (C9ORF72). How gut commensals interact with common ALS genotypes to impart risk of neural degeneration remains unclear. Here, we identify 10 phylogenetically diverse bacterial strains that promote cytokine release in a C9orf72-dependent manner. Metatranscriptomics implicated the glycogen biosynthesis pathway as a driver of inflammation. Colonization of germ-free C9orf72-deficient mice with Parabacteroides merdae that produced inflammatory glycogen enhanced monocytosis, blood-brain barrier breakdown, and T cell infiltration into the central nervous system. Enzymatic digestion of glycogen in the gut promoted survival of C9orf72-deficient mice and dampened microglial reactivity in the brain. A survey of human fecal samples demonstrated that inflammatory forms of glycogen were present in gut contents from 15/22 patients with ALS, 1/1 patient with C9ORF72 frontotemporal dementia (FTD), and 4/12 healthy controls. Together, the results of this work identify bacterial glycogen as a modifiable mediator of immune homeostasis in the gut and brain.},
}

@article {pmid41579929,
year = {2026},
author = {Murakami, K and Sudou, N and Kurata, A and Kawaguchi-Niida, M},
title = {An ALS-associated mutant SOD1 protein can be eliminated in microglia culture by selective autophagy.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.01.017},
pmid = {41579929},
issn = {1873-7544},
abstract = {The acquired toxicity of the familial amyotrophic lateral sclerosis (ALS)-associated mutant Zn-superoxide dismutase 1 (SOD1) protein has been implicated in motoneuron death, and cytosolic aggregates or inclusions have been observed in the cytoplasm of motoneurons, astrocytes, and neuronal axons but not in that of microglia. This study elucidates the mechanisms by which mutant SOD1 does not aggregate in and is cleared by microglia. We generated pcDNA3-Venus-tagged SOD1 constructs: wild-type SOD1 and mutant SOD1 were used as controls, and the A4V, D90A, and G93A SOD1 mutants were used as disease-related constructs; these plasmids were introduced into the Ra2 microglia line for subsequent evaluation. In spinal cords collected from postsymptomatic G93A mice, very little aggregation of the mutant SOD1 protein was detected in microglia, consistent with previous reports. Our new findings, which were based on immunohistochemical, Western blot, and enzyme immunoassay analyses, revealed that the protein expression of mutant SOD1 in microglia is significantly lower than that of wild-type SOD1. Furthermore, we observed the recovery of mutant SOD1 protein levels in autophagy suppression experiments and its colocalization with WDFY3, a selective autophagy-related protein. These in vitro results demonstrate that only the mutant SOD1 protein (i.e., not wild-type SOD1) is degraded by selective autophagy. Furthermore, we found that both wild-type and mutant SOD1 are secreted directly from microglia. These findings provide an opportunity to elucidate the precise mechanism through which microglia manage mutant SOD1 proteins during the pathological process of ALS and are likely to lead to improvements in ALS treatment strategies.},
}

@article {pmid41579806,
year = {2026},
author = {Sarwar, S and Mehmood, T and Iqbal, M},
title = {Advanced spectral modeling for bacterial strains: A MARS-PLS2 approach with Lasso regularization and baseline optimization.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {351},
number = {},
pages = {127506},
doi = {10.1016/j.saa.2026.127506},
pmid = {41579806},
issn = {1873-3557},
abstract = {The natural characteristics of the infrared spectroscopic data are that it tends to distort the baseline, there is high-dimensionality and non-linear correlation that hinder reliable prediction of biochemical properties. To overcome these obstacles, this study introduces an integrated MARS-PLS2-Lasso framework that incorporates the effective baseline correction, non-linear regression, latent variable extraction, and sparse variable selection to promote the chemometric modeling accuracy and interpretability. Out of four baseline correction methods, viz. Asymmetric Least Squares (ALS), AirPLS, Polynomial fitting, and Wavelet baseline correction, the Wavelet method (sym8, Level 5) was found to be the most successful, in that it was able to represent local spectral variation with low-frequency noise. This technique achieved high predictive accuracy with RMSE = 0.2846-0.6857, MAE = 0.2371-0.5445 and MSE = 0.0810-0.4705 specifying both high model fit and minimal residual error across bacterial spectra. The Wavelet-corrected spectra revealed six key functional regions that contributed most significantly to bacterial differentiation: 720cm[-1] to 750cm[-1] (C-Cl stretching, CH bending), 1000cm[-1] to 1300cm[-1] (C-O stretching, esters, carboxylic acids), 1500cm[-1] to 1650cm[-1] (CC stretching), 1687cm[-1] to 1793cm[-1] (CO stretching, conjugated carbonyls), 2771cm[-1] to 3143cm[-1] (CH stretching, alkanes, alkenes), 3290cm[-1] to 3595cm[-1] (O-H and NH stretching). Vibrational domains of interest are biochemical components of lipids, proteins, amides and polysaccharides that determine the structural integrity and metabolic activity of bacteria. The proposed MARS-PLS2-Lasso model leverages Multivariate Adaptive Regression Splines (MARS) to capture nonlinear relationships through adaptive basis functions, while Partial Least Squares (PLS2) extracts latent components that maximize covariance between spectral predictors and multiple bacterial responses. Lasso regularization adds sparsity to the model and reduces the complexity of the model, as well as penalizes less interesting basis functions, which overfit the model. Such a combination is used to provide a reasonable approximation of the parameter even in high-dimensional spectral data. In general, MARS-PLS2-Lasso provides a sound, interpretable, and chemically consistent way of high dimensional infrared spectral modeling. It is highly predictive, less noisy and has a more adequate manner of interpreting spectral-biochemical interactions, and thus, a bright way of bacteria modeling, spectral diagnostics and further use in bio-analytical spectroscopy.},
}

@article {pmid41579663,
year = {2026},
author = {Casabona, E and Cusato, J and Clari, M and Albanesi, B and Cattaneo, D and Giulio, PD and Dimonte, V},
title = {Association between anticholinergic burden scales and recurrent falls in independently living older adults: a cross-sectional study.},
journal = {Geriatric nursing (New York, N.Y.)},
volume = {69},
number = {},
pages = {103853},
doi = {10.1016/j.gerinurse.2026.103853},
pmid = {41579663},
issn = {1528-3984},
abstract = {This study examined the association between medications with anticholinergic (ACh) activity and the risk of falls in community-dwelling older adults enrolled in a home monitoring service. A cross-sectional design was applied, and logistic regression analyses were adjusted for age, sex, comorbidities, and functional status. The sample included 84 participants who had experienced at least one fall, of whom 72.6% were single fallers and 27.4% recurrent fallers (≥2 falls in 12-months of observation). Participants were divided into two groups: those taking medications (n = 55) and those not on medication (n = 29). A total of 126 falls were reported, with no significant difference in the number of falls between the two groups. The prevalence of ACh burden, assessed using ten different scales, ranged from 5.4% to 30.9% among fallers. Within the medication group, no significant differences were observed in the presence of ACh burden (≥1) between single and recurrent fallers. However, recurrent fallers in this group (n = 15) had higher scores on some scales compared with single fallers. Despite this, the discriminative ability of the ACh burden scales for identifying recurrent fallers were limited, with several, particularly the ALS and CrAS scales, failing to reach acceptable thresholds. After adjustment, the AAS scale suggested that older adults were over nine times more likely to experience recurrent falls compared with a single fall (OR=9.24; 95% CI 1.02-77.49; p = 0.004). Overall, these findings highlight the limited clinical utility of current ACh burden scales in supporting medication review as part of fall prevention strategies for older adults.},
}

@article {pmid41548000,
year = {2026},
author = {Potla, KM and Cheerlin Mishma, JN and Vankayalapati, S and Suchetan, PA and Sebastian, R and Gayatri, B and Tawfeek, AM and Alam, M and Islam, MS},
title = {Comprehensive analysis of florasulam: crystal structure, reactivity, sensitivity, and bioactivity using structural, spectroscopic, and computational approaches.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {3416},
pmid = {41548000},
issn = {2045-2322},
abstract = {UNLABELLED: The title compound, N-(2,6-difluorophenyl)-8-fluoro-5-methoxy-[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide (Florasulam), a triazolopyrimidine sulfonanilide herbicide, was investigated using experimental and computational techniques. Single-crystal X-ray diffraction revealed a V-shaped geometry stabilized by intramolecular C–F···π interactions and a unique 1D ribbon packing formed through N–H···N, C–H···O, and S = O···π interactions. Hirshfeld surface and energy framework analyses confirmed the nature and strength of intermolecular forces. DFT and TD-DFT calculations provided insights into optimized geometry, vibrational frequencies, and electronic transitions consistent with experimental spectra. The HOMO–LUMO gap indicated high chemical stability, while MEP analysis highlighted reactive sites. Autoxidation susceptibility was assessed through bond dissociation energies. Molecular docking against ALS (Acetolactate Synthase) proteins demonstrated strong binding affinity, supported by molecular dynamics simulations confirming protein–ligand complex stability. This integrative study highlights Florasulam’s potential in herbicide design.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-33458-w.},
}

@article {pmid41583971,
year = {2018},
author = {Lawson, V and Robbins, NM},
title = {The Potential Misdiagnosis of Multifocal Motor Neuropathy as Amyotrophic Lateral Sclerosis-A Case Series.},
journal = {US neurology},
volume = {14},
number = {2},
pages = {102-107},
pmid = {41583971},
issn = {1758-4000},
support = {K23 NS042713/NS/NINDS NIH HHS/United States ; },
abstract = {Multifocal motor neuropathy (MMN) is a rare neuropathy that is often treatable with immunomodulatory therapy if diagnosed early. However, accurate diagnosis is difficult due to a significant overlap of symptoms with other neurological conditions, such as amyotrophic lateral sclerosis (ALS). Evidence of immunoglobulin M (IgM) anti-ganglioside GM1 antibodies and electrodiagnostic findings of conduction block are useful diagnostic criteria for MMN but are not universal findings. This review explores the differential diagnosis of MMN and ALS and discusses three cases of MMN initially diagnosed as ALS, in which the correct diagnosis allowed effective treatment. These cases highlight the need for greater awareness of MMN among physicians.},
}

@article {pmid41579294,
year = {2026},
author = {Foffani, G and Urso, D and Hiller, J and Piccininni, M and Marin, B and Logroscino, G},
title = {The multistep pathogenic hypothesis of amyotrophic lateral sclerosis is incompatible with the epidemiological data.},
journal = {European journal of epidemiology},
volume = {},
number = {},
pages = {},
pmid = {41579294},
issn = {1573-7284},
abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease whose incidence increases with age. According to the gene-time-environment hypothesis, ALS onset occurs through the interaction between genes and environmental exposures during ageing, which may involve a continuous accumulation process. Alternatively, the multistep pathogenic hypothesis, based on the Armitage-Doll multistep model from cancer research, posits that a discrete number of specific sequential "hits" are necessary to trigger ALS. Here we analyzed three large population-based epidemiological datasets of ALS to formally test whether the ALS age-incidence curve is better described by a power law, as predicted by the Armitage-Doll model, or by an exponential function, which is generally associated to continuous accumulation of damage and is incompatible with the Armitage-Doll model. We obtained moderate-to-extreme Bayesian evidence in favor of the exponential function compared to the power law. Cancer data were instead better aligned, as expected, with the power law. These results suggest that the multistep pathogenesis hypothesis based on the Armitage-Doll model cannot be extended from cancer to ALS, because it is incompatible with the epidemiological data. This calls for a re-consideration of the current understanding of ALS pathogenesis. Our work also warns against extending the Armitage-Doll multistep model from cancer to other aging-related diseases solely based on age-incidence curves.},
}

@article {pmid41578918,
year = {2026},
author = {Silva, ST and de Queiroz Aquino, LM and Aires, DN and de Souza, AA and de Macedo, JVB and da Silva Teixeira, S and de Melo, LP and de Macedo Borges, LRD and Lindquist, ARR and de Medeiros Valentim, RA and Ribeiro, T},
title = {Pain and fatigue in amyotrophic lateral sclerosis: a multiple methods study.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/17582024.2026.2617856},
pmid = {41578918},
issn = {1758-2032},
abstract = {INTRODUCTION: Pain and fatigue are frequent symptoms in individuals with Amyotrophic Lateral Sclerosis (ALS) and the literature is controversial regarding the effectiveness of physiotherapy practices for managing these symptoms.

OBJECTIVE: To analyze the profile of pain and fatigue symptoms in a Brazilian sample with ALS and identify physiotherapy practices.

METHODS: A multimethods study composed of prospective cross-sectional design and systematic retrospective design. Data on pain and fatigue were collected and literature searches were conducted and risk of bias (PEDRro scale) and evidence quality (SIGN system) were evaluated.

RESULTS: The sample (72 individuals) had a mean score of 4.31 (pain) and 37.2 (fatigue), indicating moderate levels of symptoms. The systematic review identified various physiotherapy practices for treating pain and fatigue.

CONCLUSION: Prospective analysis of pain and fatigue profiles in individuals with ALS in Brazil revealed moderate levels of both symptoms. The systematic retrospective analysis indicated uncertainty regarding the effect of physiotherapy.},
}

@article {pmid41577334,
year = {2026},
author = {Berner, KJ and Mese, PO and Bowblis, JR and Applebaum, R},
title = {The Prevalence and Impact of Vaccination Programs: Differences Between Nursing Homes and Assisted Living Communities.},
journal = {Journal of the American Medical Directors Association},
volume = {},
number = {},
pages = {106107},
doi = {10.1016/j.jamda.2025.106107},
pmid = {41577334},
issn = {1538-9375},
abstract = {OBJECTIVES: To compare the prevalence of vaccination programs between nursing homes (NHs) and assisted living communities (ALs) and examine how these programs relate to perceived hospitalization risk and temporary admission suspensions due to outbreaks.

DESIGN: Descriptive analysis of facility-level survey data from the 2023 Ohio Biennial Survey of Long-Term Care Facilities, which has a >90% response rate.

SETTING AND PARTICIPANTS: All licensed NHs and ALs in Ohio were surveyed and answered questions related to vaccination programs (N = 736; N = 623).

METHODS: Three measures were analyzed: presence of a vaccination program for 7 vaccine-preventable illnesses (influenza; COVID-19; respiratory syncytial virus [RSV]; pneumococcal; hepatitis B; shingles; and tetanus, diphtheria, and pertussis [Tdap]), perceived risk of transferring residents to the hospital for these illnesses, and temporary suspension of admissions due to outbreaks. All measures were binary and sample averages were calculated separately for NHs and ALs. Facility characteristics associated with COVID-19-related admission suspensions were compared.

RESULTS: NHs had a higher prevalence of vaccination programs for all 7 vaccine-preventable illnesses compared with ALs. The largest differences were observed for RSV, pneumococcal, hepatitis B, shingles, and Tdap. ALs reported higher perceived risk of transferring residents to the hospital for all illnesses, whereas NHs reported the highest perceived risk for respiratory illnesses. Temporary admission suspensions due to outbreaks were uncommon; when reported, they were primarily associated with COVID-19. Facilities with COVID-19-related suspensions were more likely to be smaller and not-for-profit/government owned. NHs with outbreaks were more often located in rural areas, and ALs with outbreaks were more often located in urban areas.

CONCLUSIONS AND IMPLICATIONS: Significant disparities exist in vaccination program implementation between NHs and ALs. Expanding vaccination programs in ALs may reduce hospitalization risk and strengthen outbreak prevention. Targeted policy efforts, improved education, and resource allocation are needed to ensure equitable access to comprehensive vaccination programs across long-term care settings.},
}

@article {pmid41577127,
year = {2026},
author = {Padilla-Lichtenberger, F and Hem, S and Haumont, E and Jungberg, E and Pajanoti, G and Astur, N and Guiroy, A and Landriel, F},
title = {Spanish Translation, Cross-Cultural Adaptation & Validation of the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ) for Patients with Spinal Metastases.},
journal = {World neurosurgery},
volume = {},
number = {},
pages = {124822},
doi = {10.1016/j.wneu.2026.124822},
pmid = {41577127},
issn = {1878-8769},
abstract = {BACKGROUND: Spinal metastases significantly impair health-related quality of life (HRQoL), particularly neurological function, pain, and physical independence. The Spinal Oncology Study Group Outcome Questionnaire (SOSGOQ 2.0) is a disease-specific PROM, but no validated Spanish version exists. This study aimed to translate, culturally adapt, and validate the SOSGOQ 2.0 for Spanish-speaking patients with spinal metastases.

METHODS: Following Beaton et al.'s cross-cultural adaptation guidelines, the SOSGOQ 2.0 was forward- and back-translated, reviewed by experts, and pretested with 10 patients. Psychometric validation was performed prospectively in 81 patients. Internal consistency was assessed using Cronbach's α, test-retest reliability using intraclass correlation coefficients (ICC, n = 21), and construct validity through correlations with SF-36 and EQ-5D domains. Known-groups validity was analyzed according to neurological status (ASIA scale) and pain severity (VAS).

RESULTS: The Spanish SOSGOQ 2.0 showed excellent internal consistency (overall α = 0.89; domain range 0.70-0.93) and high test-retest reliability (ICC = 0.88; 95% CI, 0.81-0.93). Convergent validity was supported by moderate-to-strong correlations with SF-36 domains (r = 0.67-0.71). Known-groups analysis demonstrated expected differences between ambulatory (ASIA D-E) and non-ambulatory (ASIA A-C) patients, and between low (VAS ≤4) and high pain (VAS ≥5) groups. Neurological improvement post-treatment was observed in 32% of patients. The questionnaire was well understood and culturally appropriate.

CONCLUSIONS: The Spanish SOSGOQ 2.0 is a reliable and valid tool for assessing HRQoL in Spanish-speaking patients with spinal metastases, enabling standardized, disease-specific outcome measurement and supporting patient-centered care and international research collaboration.},
}

@article {pmid41577086,
year = {2026},
author = {Mercadante, S and Petronaci, A and Casuccio, A},
title = {Clinical changes in patients with amyotrophic lateral sclerosis admitted to a home care program.},
journal = {Journal of pain and symptom management},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jpainsymman.2025.12.026},
pmid = {41577086},
issn = {1873-6513},
abstract = {BACKGROUND: There is a lack of information in the literature about patients with amyotrophic lateral sclerosis (ALS) followed at home.

AIM: To characterize ALS patient demographics, longitudinal symptom trajectories, cognition, healthcare utilization, and advance care planning of an Italian home-based palliative care program cohort.

METHODS: New patients with ALS who required home palliative care were recruited for a period of one year and followed up for six months. Demographics, Karnofsky, ALS subtype, date of diagnosis, awareness, as well as ECAS (Edinburgh Cognitive and Behavioural ALS Screen) were recorded, as well as the date of diagnosis and initiation of home palliative care were collected. The use of non-invasive ventilation (NIV), mechanical ventilation by tracheostomy, gastrostomy, nasogastric tube, parenteral nutrition, were recorded at admission and during home care assistance. The existence of advance directives and shared advance care planning (ACP) was also collected. The ALS Functional Rating Scale - Revised (ALS-FRS-R) and symptom burden was measured by Edmonton Symptom Assessment System (ESAS) were measured at two-month intervals for six months.

RESULTS: Data from 34 consecutive patients with ALS admitted to palliative home care were analyzed over the period considered. While Karnofsky level significantly decreased, ECAS did not show significant changes. The need for vital supports, partcularly NIV, increased over time. Only one patient provided a ACP decision at admission, and none provided a living will. The involvement of a legal administrator facilitated the use of ACP significantly over the six months. Seven patients died at home during the first six months of home palliative care, and one patient was lost to follow-up, because they were transferred to another region. No patient was admitted to hospice in the first six months of home palliative care.

CONCLUSION: In patients with ALS admitted to home palliative care Karnofsky level, total ESAS and ALS-FRS-R score slowly but significantly decreased over six months. Only six patients died within this period. The use of NIV increased over time. No patient required hospital or hospice admission. ACP and living wills were minimal, although ACP rate increased during the study period. The program enabled patients to remain in their homes, reducing the need for hospital care.},
}

@article {pmid41575675,
year = {2026},
author = {Kopalli, SR and Wankhede, N and Rahangdale, SR and Sammeta, S and Aglawe, M and Koppula, S and Taksande, B and Upaganlawar, A and Umekar, M and Kale, M},
title = {Age-driven dysbiosis: gut microbiota in the pathogenesis and treatment of aging disorders.},
journal = {Biogerontology},
volume = {27},
number = {1},
pages = {42},
pmid = {41575675},
issn = {1573-6768},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; *Aging/physiology ; Animals ; Probiotics/therapeutic use ; },
abstract = {Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in individual neurological diseases, an aging-focused holistic synthesis has not yet been adequately developed. This review provides a critical assessment of the involvement of age-related dysbiosis of gut microbiota in the development and progression of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and cognitive aging of the elderly, and to focus on age-related microbial patterns and mechanisms of dysbiosis related to neurological aging, including inflammation and immune system dysregulation, metabolic changes, oxidative stress, barrier dysfunction, and gut-brain communication through enteroendocrine, enteric neural, and vagal mechanisms, and to emphasize disease-specific and common microbial patterns of dysbiosis and beneficial and harmful microbial roles in aging diseases. This review assesses some of the latest promising therapies aimed at the microbiota, such as probiotics, prebiotics, dietary therapies, fecal microbiota transplantation, as well as pharmacological therapies, and critically discusses their limitations in terms of interindividual variability and their generalisation and applicability. Focusing on mechanistic, comparative, and translation aspects, this review offers a comprehensive approach to neurological aging due to gut microbiota and identifies gaps for future precision microbiome-based interventions.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Dysbiosis/therapy/microbiology
*Aging/physiology
Animals
Probiotics/therapeutic use

@article {pmid41574092,
year = {2026},
author = {Khurana, S and Gourie-Devi, M and Vats, Y and Verma, S and Ganguly, NK and Chugh, P and Sharma, A and Khanna, L and Dhawan, U and Taneja, V},
title = {Clinical and genetic determinants of survival in amyotrophic lateral sclerosis patients from North India.},
journal = {Brain communications},
volume = {8},
number = {1},
pages = {fcag003},
pmid = {41574092},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, with significant clinical and genetic variability. While the role of genetic factors is well-established in ALS pathogenesis, their impact on survival outcomes remains poorly understood, particularly in the Indian population. We performed whole-exome sequencing in 159 ALS patients from North India (familial = 2, sporadic = 157). Clinical parameters, including age at onset, site of onset, sex, family history and survival, were recorded. Males exhibited shorter survival than females, but did not achieve statistical significance (median: 48 versus 60 years, P = 0.05). Bulbar-onset patients developed ALS at a significantly older age (mean: 59.7 versus 54 years, P = 0.007) and experienced poorer survival outcomes than spinal-onset patients (median: 48 versus 60 months, P = 0.03). A small subset of ALS patients (6.3%, n = 10) had very long survival duration of more than 10 years. We identified 102 genetic variants in 92 ALS patients, of which 45 variants were novel. According to American College of Medical Genetics and Genomics guidelines, 13.5% of total variants were pathogenic, 19.8% were likely pathogenic, and 66.7% were variants of uncertain significance. The presence of genetic variations was significantly associated with delayed onset (mean: 53.4 versus 57.1 years, P = 0.049) and diminished life expectancy (median: 48 versus 60 months, P = 0.029). Variations in more than one gene were detected in 16.7% of the patients, supporting the theory of oligogenic basis for ALS. After adjusting for age at onset, increased risk of mortality was associated with males [hazard ratio = 1.740, 95% confidence interval (CI) = 1.105-2.740] and rare genetic variations (hazard ratio = 1.533, 95% CI = 1.001-2.350). Furthermore, bulbar onset (hazard ratio = 1.75, 95% CI = 1.11-2.75) was found to be a negative prognostic factor for survival. Our study provides valuable insights into the genetic complexity and its impact on clinical outcomes in ALS patients of North Indian origin.},
}

@article {pmid41573891,
year = {2025},
author = {Gomberg, TA and Elmsaouri, S and Kopalle, HM and Baughn, MW and Beccari, MS and McAlonis-Downes, M and Artates, JW and Pant, D and Mak, H and Smargon, AA and Sander, TC and Garcia, E and Lee, DP and Cleveland, DW and Yeo, GW},
title = {Dual-targeting snRNA gene therapy rescues STMN2 and UNC13A splicing in TDP-43 proteinopathies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.01.691001},
pmid = {41573891},
issn = {2692-8205},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder caused by the selective deterioration of motor neurons in the central nervous system (CNS). A key driver of this pathogenesis is nuclear loss of ALS-associated protein TDP-43, leading to mis-splicing of TDP-43 targets including important neuronal genes STMN2 and UNC13A . Here, we have developed a gene therapy strategy for ALS and related TDP-43 proteinopathies, to correct mis-splicing of both STMN2 and UNC13A cryptic exons using small nuclear RNAs (snRNAs) encoded from a single vector. We identified promoter sequence elements to increase therapeutic snRNA expression by 10-fold, then further optimized the expression cassette with combinatorial snRNA targeting to rescue multiple cryptic splicing targets. The engineered snRNAs restored normal pre-mRNA processing of both STMN2 and UNC13A transcripts despite TDP-43 loss of function, rescuing stathmin-2 protein levels in iPSC derived motor neurons, restoring their axonal regeneration capacity to wild-type levels. In addition, adeno-associated virus (AAV) delivery of the snRNAs to the murine central nervous system in the constitutive cryptic splicing model Stmn2 [HumΔGU] fully restored cortical Stmn2 pre-mRNA processing, highlighting the utility of snRNAs as a therapeutic modality in vivo . Together, this study demonstrates that snRNAs are a promising and versatile therapeutic strategy for the simultaneous correction of multiple aberrant transcripts affected by cryptic splicing in TDP-43 proteinopathies.},
}

@article {pmid41573237,
year = {2026},
author = {Triyono, T and Nita, RW and Suarja, S and Handayani, PG and Feberiani, RD and Hidayat, H},
title = {Self-Efficacy as the Key Mechanism in Student Help-Seeking: A Commentary on Patricio et al (2025).},
journal = {Chronic stress (Thousand Oaks, Calif.)},
volume = {10},
number = {},
pages = {24705470261416642},
pmid = {41573237},
issn = {2470-5470},
abstract = {This commentary highlights the significance of Patricio et al.'s (2025) findings on the mediating role of self-efficacy in the relationship between shyness and help-seeking among Filipino college students. The study challenges assumptions that shyness directly hinders help-seeking and emphasizes the cultural influence of hiya. Notably, self-efficacy mediates help-seeking for suicidal ideation, underscoring its importance in high-risk situations and its relevance for suicide-prevention initiatives in higher education. We further discuss the roles of stigma, social support, and cultural expectations, as well as the need for gender-sensitive research. The commentary advocates culturally grounded interventions to strengthen student mental-health help-seeking.},
}

@article {pmid41572777,
year = {2026},
author = {Liu, X and Lv, Z and Xu, G and Chen, Y and Liu, H and Xu, P},
title = {Investigating the Multiple Regulatory Mechanisms and Therapeutic Targets of PHLDA1 in Neurological Diseases.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X413561251125064110},
pmid = {41572777},
issn = {1875-6190},
abstract = {PHLDA1 (pleckstrin homology-like domain family A member 1) is a pleiotropic regulatory protein that affects key biological processes such as apoptosis, pyroptosis, immune inflammation, autophagy, metabolism, and oxidative stress. PHLDA1 plays a significant role in the pathological mechanisms of neurological diseases. This article systematically reviews the molecular characteristics of PHLDA1 and its core role in cerebrovascular diseases such as cerebral ischemia/ reperfusion injury, cerebral hemorrhage, subarachnoid hemorrhage, epilepsy, amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Studies have shown that PHLDA1 promotes disease progression by regulating signalling pathways such as the NF-κB, MAPK, NLRP3 inflammasome, PPARγ, and Nrf2 pathways, thereby exacerbating neuroinflammation, mitochondrial dysfunction, endoplasmic reticulum stress, and pyroptosis in neurons. Its expression is regulated by the dynamic balance of miRNAs (such as miR-194 and miR-101), transcription factors (Egr1 and BHLHE40), and heat shock proteins (HSPs/HSF1). In addition, PHLDA1 has become a potential target for intervention in neurodegenerative and ischemic injuries by inhibiting FundC1-mediated mitochondrial autophagy, regulating microglial polarization, and activating TRAF6-dependent neuroinflammation. This article not only clarifies the pathogenic mechanism of PHLDA1 but also summarizes the relevant intervention strategies targeting PHLDA1, hoping to provide a corresponding theoretical basis and reference for the development of precision therapies for neurological diseases.},
}

@article {pmid41572578,
year = {2026},
author = {She, JW and Lin, LA and Aerathupalathu Janardhanan, J and Wang, IC and Hsu, FC and Tseng, HS and Hsiao, YS and Yu, HH},
title = {Precision Channel Engineering of Nanotube-Embedded Organic Electrochemical Transistors for Ultrasensitive Neurofilament Light Chain Detection.},
journal = {ACS applied bio materials},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsabm.5c02404},
pmid = {41572578},
issn = {2576-6422},
abstract = {The quantitative monitoring of neurofilament light chain (Nf-L) is critical for the early diagnosis and prognosis of neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), yet achieving femtomolar sensitivity in a portable, label-free format remains a formidable challenge. Here, we report a high-performance organic electrochemical transistor (OECT) immunosensor engineered via the precise template-free electropolymerization of a dual-functional poly(EDOT-COOH-co-EDOT-EG3) copolymer. By systematically modulating the polymerization kinetics, we elucidated a decisive structure-function relationship governing biosensing efficacy: while microstructured channels formed at longer deposition times exhibited superior intrinsic transconductance due to maximized volumetric capacitance, the optimized nanotubular architecture provided the ideal balance of open porosity and accessible surface area. This specific nanotopography facilitated a significantly higher density of covalent antibody immobilization compared to its microstructured counterpart, thereby dominating the signal transduction mechanism through enhanced dielectric barrier formation upon antigen binding. Capitalizing on this morphology-governed sensitivity, the platform achieved a theoretical limit of detection (LOD) of 0.062 fg/mL (3σ criterion) and a rigorous LOD of 32.77 fg/mL (Hubaux-Vos method) across a broad dynamic range, along with exceptional selectivity and operational stability over 500 cycles. These findings underscore the critical role of precision channel engineering in bioelectronics, establishing a robust, lithography-free pathway for next-generation point-of-care diagnostics targeting diseases.},
}

@article {pmid41572495,
year = {2026},
author = {Zaman, A and Drake, SS and Fournier, AE},
title = {Extracellular Vesicle-Derived microRNAs as Fluid Biomarkers in Neurodegenerative Diseases: A Systematic Review.},
journal = {Journal of neurochemistry},
volume = {170},
number = {1},
pages = {e70323},
doi = {10.1111/jnc.70323},
pmid = {41572495},
issn = {1471-4159},
support = {//MS Canada/ ; /CAPMC/CIHR/Canada ; //Fonds de Recherche du Québec - Santé/ ; //Myelin Repair Foundation/ ; //Fonds de recherche du Québec/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/genetics/cerebrospinal fluid/blood/metabolism ; *Extracellular Vesicles/metabolism/genetics ; *MicroRNAs/cerebrospinal fluid/metabolism/blood ; Biomarkers/cerebrospinal fluid/blood/metabolism ; Animals ; },
abstract = {Given the absence of curative treatments for neurodegenerative diseases, early detection and therapeutic intervention are critical to slowing disease progression. Extracellular vesicles (EVs) have emerged as promising biomarkers for neurodegeneration, owing to their accessibility in bodily fluids and dynamic molecular cargo, including microRNAs (miRNAs). The last decade has seen accumulating evidence for miRNA dysregulation in circulating EVs from people with neurodegenerative diseases; however, assessing reproducibility between studies remains challenging, largely due to clinical and methodological heterogeneity. In this systematic review, we comprehensively searched the MEDLINE database for studies investigating miRNA expression in biofluids from people with neurodegenerative diseases. We extracted miRNA expression data from 185 peer-reviewed publications, published until June of 2025, reporting altered miRNA levels in fluid-derived EVs from people with neurodegenerative diseases. We consolidated results between studies to identify the most frequently dysregulated miRNAs across diseases, with a focus on Alzheimer's disease, Parkinson's disease, mild cognitive impairment, multiple sclerosis, amyotrophic lateral sclerosis, frontotemporal dementia, stroke, traumatic brain injury, and schizophrenia. Evaluating tissue specificity of frequently dysregulated miRNAs revealed enrichment of select miRNAs in the nervous system relative to blood and immune compartments. Summarizing miRNA regulation across biofluids emphasized consistencies between cerebrospinal fluid and plasma, but not serum. We highlight circulating miRNAs that may be reflective of neuropathology, including miR-143-3p, miR-127-3p, miR-9-5p, miR-15a-5p, and miR-125b-5p. Finally, we provide a repository of miRNA expression data from over 30 neurodegenerative conditions which can be exploited to further investigate miRNA regulation in diseases of interest.},
}

Humans
*Neurodegenerative Diseases/diagnosis/genetics/cerebrospinal fluid/blood/metabolism
*Extracellular Vesicles/metabolism/genetics
*MicroRNAs/cerebrospinal fluid/metabolism/blood
Biomarkers/cerebrospinal fluid/blood/metabolism
Animals

@article {pmid41572285,
year = {2026},
author = {Straczkiewicz, M and Burke, KM and Calcagno, N and Premasiri, A and Carney, KT and Vieira, FG and Onnela, JP and Berry, JD},
title = {Short prescribed exercises can quantify upper limb functioning in neurodegenerative disease.},
journal = {Journal of neuroengineering and rehabilitation},
volume = {23},
number = {1},
pages = {28},
pmid = {41572285},
issn = {1743-0003},
mesh = {Humans ; Male ; Female ; *Upper Extremity/physiopathology ; Middle Aged ; Accelerometry ; Longitudinal Studies ; Aged ; *Exercise Therapy/methods ; *Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology ; Wearable Electronic Devices ; },
abstract = {BACKGROUND: Digital health technologies (DHTs) can quantify movements in daily routines but rely heavily on participant adherence over prolonged wear times.

METHODS: We analyzed accelerometry data from wrist-worn devices during short at-home episodes of prescribed exercises performed by 329 individuals living with amyotrophic lateral sclerosis (ALS) in a longitudinal study. We developed an automated and interpretable signal processing method to estimate four metrics describing exercise repetitions, i.e., their count, duration, intensity, and similarity. We examined their associations with time elapsed from enrollment and ALS Functional Rating Scale-Revised (ALSFRS-R) using linear mixed effect models. We also compared them with previously validated free-living metrics that require substantial sensor wear-time. Finally, we studied how many repetitions are sufficient to determine participants' upper limb functioning.

RESULTS: Three out of four exercise metrics (all but count) demonstrated significant association with ALSFRS-R outcomes. The duration of exercise repetitions increased, while intensity and similarity of movement decreased over time (all p-value < 0.001), indicating longer but less vigorous and less consistent upper limb movements over time. Exercise intensity was determined as the most robust exercise-based predictor of changes in upper limb function, and it was comparable to free-living metrics, which required at 21 h of sensor wear time (R-squared 0.899 vs. 0.860, respectively). Sensitivity analysis indicated that as few as five exercise repetitions were sufficient to yield statistically significant associations with ALSFRS-R.

CONCLUSIONS: These results suggest that prescribed exercise can effectively quantify upper limb function and track longitudinal decline comparably to free-living observation. The proposed method may serve as an alternative that decreases participation burden, increases study adherence, and extends diagnostic accessibility.},
}

Humans
Male
Female
*Upper Extremity/physiopathology
Middle Aged
Accelerometry
Longitudinal Studies
Aged
*Exercise Therapy/methods
*Amyotrophic Lateral Sclerosis/rehabilitation/physiopathology
Wearable Electronic Devices

@article {pmid41571890,
year = {2026},
author = {Lee, J and Lee, GR and Lee, HI and Kwon, M and Kim, T and Lee, JR and Lee, SY and Jeong, W},
title = {Rgnef regulates bone mass through the activation of RhoA and Rac1.},
journal = {Experimental & molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {41571890},
issn = {2092-6413},
support = {RS-2024-00357657//National Research Foundation of Korea (NRF)/ ; RS-2023-00217798//National Research Foundation of Korea (NRF)/ ; 2019R1A6C1010020//Korea Basic Science Institute (KBSI)/ ; RP-Grant 2022//Ewha Womans University (Ewha)/ ; },
abstract = {Rho guanine nucleotide exchange factor (Rgnef/p190RhoGEF), a RhoA-specific guanine nucleotide exchange factor, has been implicated in cancer and amyotrophic lateral sclerosis, but little is known about its role in bone. Here we investigate the roles of Rgnef in bone metabolism using Rgnef-deficient and overexpressing mice. Compared with littermate wildtype mice, Rgnef-deficient mice had increased bone mass owing to lower osteolysis and higher osteogenesis, and Rgnef-overexpressing transgenic mice had the opposite bone phenotype. Rgnef deficiency inhibited osteoclast formation and resorptive function and promoted osteoblast differentiation and mineralization, whereas Rgnef overexpression had the reverse effect. Mechanistically, Rgnef promotes osteoclastogenesis by enhancing the activity of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases and AKT through the activation of RhoA and Rac1 and attenuates osteoblastogenesis through the RhoA/Rac1-mediated NF-κB activation. Moreover, Rgnef-deficient mice were protected from bone loss caused by lipopolysaccharide-induced inflammation or ovariectomy. Thus, Rgnef is a crucial regulator of bone metabolism and could serve as a potential new target for treating bone diseases.},
}

@article {pmid41571758,
year = {2026},
author = {Lacour, A and Vassallu, F and Romussi, S and Rayes, D and Igaz, LM},
title = {Cytoplasmic TDP-43 leads to early behavioral impairments without neurodegeneration in a serotonergic neuron-specific C. elegans model.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-36138-5},
pmid = {41571758},
issn = {2045-2322},
support = {PICT 2019-0480 (To DR)//Agencia Nacional de Promoción de la Ciencia y la Tecnología ANPCYT Argentina/ ; PICT 2019-1585 (To LMI)//Agencia Nacional de Promoción de la Ciencia y la Tecnología ANPCYT Argentina/ ; PIP No. 11220200101606CO (To DR)//Consejo Nacional de Investigaciones Científicas y Técnicas/ ; PGI: 24/B291 (To DR)//Universidad Nacional del Sur/ ; },
abstract = {TDP-43 proteinopathies, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are marked by the pathological cytoplasmic accumulation of TAR DNA-binding protein 43 (TDP-43), leading to progressive neuronal dysfunction and degeneration. To investigate the early functional consequences of TDP-43 mislocalization, we generated Caenorhabditis elegans models expressing either wild-type human TDP-43 or a variant with a mutated nuclear localization signal (ΔNLS), specifically in serotonergic neurons. These neurons were chosen because in C. elegans they regulate well-characterized behaviors, providing a straightforward readout of neuronal function. We found that expression of either TDP-43 variant impaired serotonin-dependent behaviors-including pharyngeal pumping, egg-laying, and locomotion slowing upon food encounter-with the cytoplasmic ΔNLS form causing more severe deficits. These behavioral impairments are evident even while the serotonergic neurons remain apparently normal in structure, suggesting that neuronal dysfunction precedes overt neurodegeneration. Moreover, the serotonergic HSN neurons that control egg-laying were also partially responsive to the selective serotonin reuptake inhibitor fluoxetine, suggesting that neurotransmitter release remains functional to some extent. Altogether, our findings demonstrate that TDP-43 expression causes neuronal dysfunction leading to behavioral deficits, even in the absence of detectable structural pathology and that its mislocalization to the cytoplasm results in more severe behavioral impairments. This C. elegans model provides a genetically tractable system to dissect early mechanisms of TDP-43-mediated neuronal dysfunction and to identify therapeutic strategies targeting predegenerative stages of ALS/FTD.},
}

@article {pmid41571168,
year = {2026},
author = {Malvandi, AM and Gerosa, L and Maroni, P and Orlando, ME and Mohammadipour, A and Lombardi, G},
title = {miRNA-206 in crosstalk muscle and central nervous system pathophysiology during exercise: a double-edged sword with therapeutic potential.},
journal = {Neuroscience and biobehavioral reviews},
volume = {},
number = {},
pages = {106569},
doi = {10.1016/j.neubiorev.2026.106569},
pmid = {41571168},
issn = {1873-7528},
abstract = {Physical activity triggers complex molecular responses in skeletal muscle, with increasing evidence showing systemic signaling roles for muscle-derived microRNAs (myomiRs). Among these, miR-206 has attracted attention for its dual function: promoting muscle regeneration but potentially harming the central nervous system (CNS). This review examines how miR-206 expression is regulated during exercise and its effects on muscle biology-such as fiber-type specification, mitochondrial changes, and neuromuscular junction (NMJ) repair. It also explores the paradoxical effects of high miR-206 levels in the CNS, where it targets brain-derived neurotrophic factor (BDNF), reducing neuroplasticity and increasing vulnerability to neuropsychiatric and neurodegenerative diseases. The review highlights disease-specific aspects, showing miR-206 as harmful in Alzheimer's, stroke, and depression, but potentially protective in amyotrophic lateral sclerosis (ALS). We discuss its potential as a biomarker and therapeutic target, stressing tissue-specific regulation approaches. Overall, miR-206 plays a key role in muscle-brain communication, with important implications for exercise, aging, and CNS disorders.},
}

@article {pmid41570741,
year = {2026},
author = {Genin, EC and Paquis-Flucklinger, V},
title = {ALS-related proteinopathies: From TDP-43 to mitochondrial proteinopathies.},
journal = {Current opinion in neurobiology},
volume = {97},
number = {},
pages = {103163},
doi = {10.1016/j.conb.2025.103163},
pmid = {41570741},
issn = {1873-6882},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons. ALS often overlaps clinically and pathologically with frontotemporal dementia (FTD), the second most common form of dementia. Like many neurodegenerative disorders, both ALS and FTD share a crucial pathological hallmark, the aggregation of misfolded proteins into insoluble inclusions in degenerating neurons. This process is referred to as proteinopathy. This review focuses on the proteinopathies associated with ALS, including aggregates of TDP-43, SOD1, FUS, and CHCHD10, which disrupt critical cellular processes such as RNA metabolism, mitochondrial function, and protein homeostasis. The review highlights to the identification of new types of mitochondrial and cytosolic aggregates linked to CHCHD10-related ALS. Although the precise pathological mechanisms remain to be fully elucidated, strategies aimed at restoring proteostasis and reducing protein aggregation may be promising therapeutic approaches for treating ALS, as they directly target fundamental pathogenic mechanisms.},
}

@article {pmid41569987,
year = {2026},
author = {Wang, WR and Liu, GD and Ren, DX and Liu, XY},
title = {Allostatic load in thyroid cancer is higher than that of other cancers: A secondary analysis using NHANES.},
journal = {PloS one},
volume = {21},
number = {1},
pages = {e0341063},
pmid = {41569987},
issn = {1932-6203},
mesh = {Humans ; *Thyroid Neoplasms/physiopathology/pathology ; Female ; Male ; Middle Aged ; Cross-Sectional Studies ; Nutrition Surveys ; *Allostasis/physiology ; Adult ; Aged ; ROC Curve ; },
abstract = {BACKGROUND: To compare the levels of allostatic load score (ALS) between thyroid cancer patients and patients with other types of cancer and explore whether ALS mediates the association between thyroid cancer and alterations in physiological function.

METHODS: This cross-sectional study conducted a secondary analysis of 181 cancer patients using NHANES data from 2007 to 2020, including 91 individuals with thyroid cancer. Generalized linear regression, logistic regression, and sensitivity analysis were used to analyze the association between thyroid cancer and ALS in three different models. Receiver operating characteristic (ROC) curve analysis and feature importance analysis were utilized to assess the clinical predictive value of thyroid cancer. We also conducted a series of mediation analyses to examine the mediating role of ALS.

RESULTS: The ALS in thyroid cancer patients was higher than that in other cancer types (P < 0.05). Thyroid cancer was significantly associated with ALS even after adjusting for demographic variables (β = 0.770, 95%CI: 0.315-1.480; OR=2.255, 95%CI: 1.111-4.575). This association remained robust to missing data (all P < 0.05) and was not confounded by drinking, diabetes, or thyroid disease (all P > 0.05). Although thyroid cancer had limited predictive value on ALS, it exerted strong explanatory power. The mediation analysis conducted with imputed data and adjusted for confounding variables revealed that ALS fully mediated the effect of thyroid cancer on red cell distribution width (RDW) (IE: β = 0.103, P = 0.008; DE: β = 0.389, P = 0.056), with a mediation proportion of 20.93%.

CONCLUSION: Our findings revealed that thyroid cancer condition were associated with elevated AL. AL mediated the relationship between thyroid cancer and RDW.},
}

Humans
*Thyroid Neoplasms/physiopathology/pathology
Female
Male
Middle Aged
Cross-Sectional Studies
Nutrition Surveys
*Allostasis/physiology
Adult
Aged
ROC Curve

@article {pmid41569660,
year = {2026},
author = {Özkan, B and Ramge, JM and Wiesner, D and Scekic-Zahirovic, J and Antonucci, S and Nungeß, S and Gebauer, D and Ignatius, A and Weishaupt, JH and Haffner-Luntzer, M and Roselli, F},
title = {Reduced osteogenic factors and early osteoblast senescence in SOD1(G93A) ALS mouse model.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.197475},
pmid = {41569660},
issn = {2379-3708},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease. Emerging evidence suggests manifestations beyond the neuromuscular system. Bone alterations are part of the ALS clinical picture; it remains unclear whether they are secondary to muscle denervation or due to an autonomous process. We investigated skeletal involvement in the SOD1(G93A) mouse model at presymptomatic (P45) and symptomatic (P110) stage through biomechanical and transcriptomic approaches. Three-point bending revealed significant reductions in femoral rigidity and maximum bending force in SOD1 mutants at P45, indicating early structural deficits. Micro-CT analysis demonstrated reduced trabecular bone mineral density and thickness at P45, with progressive trabecular loss and cortical thinning by P110. Histological examination revealed marked osteoblast loss at P45 suggesting impaired bone formation as the primary early mechanism. Transcriptomics of bulk bone and cultured osteoblasts from P45 mice identified dysregulation of bone differentiation, including downregulation of osteoblast differentiation genes and upregulation of negative regulators of ossification and increased cell senescence signatures. Unfolded protein response was upregulated in SOD1 osteoblasts. Immunohistochemistry confirmed the senescence phenotype with increased p16Ink4a level in SOD1 osteoblasts. These findings suggest that bone deterioration precede overt motor symptoms and are linked to osteoblast premature senescence.},
}

@article {pmid41569391,
year = {2026},
author = {Raymond, KF and Hodge, T and St Jean, B and Liu, BF},
title = {Barriers to Long COVID Care in the U.S.: An Application of Levesque et al.'s Access Framework.},
journal = {Health care analysis : HCA : journal of health philosophy and policy},
volume = {},
number = {},
pages = {},
pmid = {41569391},
issn = {1573-3394},
support = {Pandemic Readiness Initiative//University of Maryland/ ; Pandemic Readiness Initiative//University of Maryland/ ; },
abstract = {Long COVID is a condition that arose during the COVID-19 pandemic in individuals who developed the multi-system chronic condition after a COVID-19 infection. During the pandemic in the United States (U.S.), these "COVID long-haulers" navigated a complex and overburdened health care system in pursuit of diagnoses and treatments. This qualitative secondary analysis used the 2013 Levesque et al. Conceptual Model of Healthcare Access to examine multidimensional health care access issues faced by 29 COVID long-haulers in the U.S. Our analysis showed that long-haulers faced complementary issues from both individual and health systems perspectives related to the inability to get diagnoses or treatments, long waiting times for providers and difficulty reaching services, underinformed providers and biased interpersonal experiences, and struggles with the financial costs of treating the condition, which impacted care decisions. Interviewees also described relying on alternative medicine to provide symptom relief. Overall, this study extends international research by offering a comprehensive examination of Long COVID health care access issues in the U.S. and identifying specific insights related to health care access that made obtaining Long COVID care difficult, such as the mismatch between individual expectations of what health care should look like and how it actually operates. Our use of the full Conceptual Model of Healthcare Access provides new insights into the overlap across layers of access issues and offers suggestions for how public health and clinical health practitioners can collaborate to meet the needs of vulnerable populations such as these in future health emergencies.},
}

@article {pmid41569095,
year = {2026},
author = {Charbonnel, T and Richard, E and Dupuis, A and Palla, M and Vourc'h, P and Corcia, P and Al Ojaimi, Y and Blasco, H},
title = {The preclinical discovery and development of edaravone for the treatment of amyotrophic lateral sclerosis: what lessons have we learnt?.},
journal = {Expert opinion on drug discovery},
volume = {},
number = {},
pages = {},
doi = {10.1080/17460441.2026.2619067},
pmid = {41569095},
issn = {1746-045X},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, with limited therapeutic options. Among the few approved drugs, edaravone, a free radical scavenger developed originally for ischemic stroke, has attracted particular attention for its ability to counteract oxidative stress, a key driver of neurodegeneration. Its amphipathic structure and ability to cross the blood - brain barrier support its potential neuroprotective action.

AREAS COVERED: The authors discuss the preclinical studies that demonstrated edaravone's ability to reduce oxidative damage, preserve mitochondrial function, and modulate neuroinflammatory responses in cellular and animal models of ALS. They also discuss the variations in dosage, timing, and disease models that have so far produced heterogeneous results. In transgenic mice, edaravone may delay symptom onset and modestly extend survival, but these effects remain inconsistent and often restricted to early disease stages.

EXPERT OPINION: Clinically, edaravone provides only modest benefits in a subset of patients, reflecting the translational gap between preclinical efficacy and clinical relevance. This case highlights broader challenges of ALS drug discovery, including limited model predictivity, methodological variability, and the lack of patient stratification.The edaravone experience highlights key lessons for future neuroprotective approaches: the importance of standardized preclinical design, integration of human-based models, early pharmacokinetic validation, and biomarker-driven trials to advance precision neuroprotection in ALS.},
}

@article {pmid40971912,
year = {2026},
author = {Zhang, G and Ma, Y and Liu, Z and Jin, L and Zheng, D and Zhang, X and Jin, G},
title = {Intraocular lens power calculation formula accuracy in 1178 eyes with short axial length: systematic review and network meta-analysis.},
journal = {Journal of cataract and refractive surgery},
volume = {52},
number = {2},
pages = {202-207},
pmid = {40971912},
issn = {1873-4502},
mesh = {Humans ; *Axial Length, Eye/pathology ; *Biometry/methods ; *Lens Implantation, Intraocular ; *Lenses, Intraocular ; *Optics and Photonics ; *Refraction, Ocular/physiology ; },
abstract = {TOPIC: To systematically review the literature and conduct a comprehensive quantitative analysis to compare the accuracy of different intraocular lens (IOL) calculation formulas in eyes with short axial lengths (ALs).

CLINICAL RELEVANCE: The precision of the IOL formulas decreases when applied in eyes with short AL (AL <22 mm), and many new formulas for calculating IOL power have been proposed in the past few decades. However, the accuracy of these formulas has not been systematically compared when applied in eyes with short AL.

METHODS: This study systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases to collect relevant research literature published between January 2003 and September 2023. Included were prospective or retrospective clinical studies involving cataract patients with short AL (AL <22 mm) and reporting the following outcomes: mean absolute error, median absolute error (MedAE), and percentage of eyes with a prediction error (PE) within ±0.25 diopters (D), ±0.50 D, and ±1.00 D. A network meta-analysis was performed using R software (v. 4.2.1).

RESULTS: 15 prospective or retrospective studies involving 1178 eyes and 12 calculation formulas were included in this study. The network meta-analysis showed that compared with the widely used Haigis formula, the Kane formula had a higher percentage of eyes with PE within the range of ±0.25 D, ±0.50 D, and ±1.00 D (all odds ratio >1, but P > .05). In addition, based on the surface under the cumulative ranking area (SUCRA), the Kane formula had the highest probability of predicting the PE of the eyes within the range of ±0.25 D, with its SUCRA value of 95.74%, followed by Haigis formula (94.79%) and Olsen Standalone formula (84.04%). The Kane and Olsen Standalone formulas had the lowest MedAE.

CONCLUSIONS: The Kane, Haigis, and Olsen Standalone formulas may perform better than other formulas in calculating the IOLs power in eyes with short AL. Nonetheless, significant uncertainty remains in this area. The accuracy of these formulas in patients with short AL needs to be verified by large multicenter registry studies.},
}

Humans
*Axial Length, Eye/pathology
*Biometry/methods
*Lens Implantation, Intraocular
*Lenses, Intraocular
*Optics and Photonics
*Refraction, Ocular/physiology

@article {pmid41567979,
year = {2025},
author = {Hamdalla, RH and Bhaskar, VB and Tian, C},
title = {Brain-derived extracellular vesicles potentially mediate crosstalk with peripheral organs in neurodegenerative diseases.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1710150},
pmid = {41567979},
issn = {2296-634X},
abstract = {Brain-Derived Extracellular vesicles (BDEVs) are emerging mediators of intra- and interorgan communication in neurodegenerative diseases (NDs) such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). A growing body of evidence suggests that BDEVs play an important role in modulating intercellular communication within the central nervous system in the pathogenesis of many NDs. By transporting non-coding RNAs (e.g., miRNAs) and important pathological proteins, BDEVs also influence peripheral organs and contribute to the progression of disease in the central nervous system (CNS). This review extends the understanding of NDs beyond solely brain dysfunction and gives a novel framework for the progression of these diseases, uniquely emphasizing the currently underexplored mechanisms by which BDEV-mediated communication exacerbates or potentially initiates peripheral dysfunction or complications. It maps and clarifies the specific and potential mechanisms by which CNS-originating EV activity proliferates systemic dysfunction, presenting new opportunities and areas for therapeutic and diagnostic treatments for NDs. These findings are contextualized across multiple NDs, including Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease (HD), and Multiple Sclerosis (MS), by incorporating data on dysregulated BDEV miRNAs and toxic proteins to map the pathway of BDEV-mediated disease spread.},
}

@article {pmid41565509,
year = {2026},
author = {Lee, NC and Lin, CH and Chien, YH and Hwu, WL},
title = {Genetic testing for adult-onset neurodegenerative diseases: A clinical perspective.},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2026.01.021},
pmid = {41565509},
issn = {0929-6646},
abstract = {Adult-onset neurodegenerative diseases (AOND), such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, severely affect patients' quality of life. Pathogenic single-nucleotide variations (SNVs) and small insertions and deletions (indels) can disrupt genes involving ANOD, and expansion of short tandem repeats such as trinucleotide repeats is an important etiology of hereditary ataxia. Variations in more than one gene combined to create polygenic risk scores (PRS) for multifactorial types of AOND. Recently, genome structural variations (SVs) like copy number variations (CNVs) and expansion of long repeats are increasingly identified as the etiologies of AOND. Tools for molecular diagnosis of AOND have evolved from Sanger sequencing to next-generation sequencing (NGS) such as short-read whole-exome sequencing (WES) and whole-genome sequencing (WGS), and long-read sequencing is especially helpful in solving SVs and expansions of long repeats. Patients might have affected and/or at-risk family members at the time of diagnosis, so genetic counseling for risk handling and birth planning need to be conducted with caution. This review will help readers to better understand the genetic testing for AOND.},
}

@article {pmid41565302,
year = {2026},
author = {Warita, H and Urushitani, M and Atsuta, N and Izumi, Y and Kano, O and Shimizu, T and Nakayama, Y and Narita, Y and Nodera, H and Fujita, T and Mizoguchi, K and Morita, M and Aoki, M},
title = {Addendum to the 2023 clinical practice guidelines for amyotrophic lateral sclerosis in Japan: approval and integration of novel disease-modifying therapies.},
journal = {Rinsho shinkeigaku = Clinical neurology},
volume = {},
number = {},
pages = {},
doi = {10.5692/clinicalneurol.cn-002198},
pmid = {41565302},
issn = {1882-0654},
abstract = {Amyotrophic lateral sclerosis (ALS) is an intractable motor neuron disease characterized by progressive degeneration of motor neurons with varying degrees of frontotemporal lobe dysfunction. This English summary of the addendum to the Japanese clinical practice guidelines for ALS outlines major recent advances in pharmacological therapy in Japan. Following the development of the 2023 guidelines, three additional medications-oral edaravone, high-dose intramuscular mecobalamin, and tofersen-have been introduced. Oral edaravone, with its ease of administration, demonstrates pharmacokinetics comparable to the intravenous formulation. High-dose mecobalamin reduces functional decline when initiated early in the disease course. Tofersen, an antisense oligonucleotide, is the first gene-targeted therapy approved in Japan for patients with copper/zinc superoxide dismutase gene-related ALS, highlighting the importance of genetic testing and counseling in all ALS cases. This addendum provides updated expert consensus recommendations for the use, dosing, and monitoring of these therapies, while emphasizing the need for thorough communication about the ethical and psychological dimensions of genetic testing. It also addresses practical considerations for combination therapy, noting that up to three or four anti-ALS agents are now available in Japan. The long-term safety and efficacy of these therapies, as well as their potential synergistic or additive effects, remain to be clarified through real-world data and prospective registries. The objectives of this addendum are twofold: to present these advances and recommendations in English to foster international collaboration, and to inform the global ALS community about the latest therapeutic strategies in Japan. In addition, ongoing efforts to harmonize clinical evaluation standards and promote international clinical trials are highlighted, with the goal of improving patient outcomes and advancing ALS research worldwide.},
}