@article {pmid42508631,
year = {2026},
author = {Alanazi, SM and Al-Kuraishy, HM and Alexiou, A and Papadakis, M and Faheem, SA and Batiha, GE},
title = {Isoform-selective HSP90 inhibition as a precision therapeutic strategy for neurodegenerative and metabolic diseases.},
journal = {Progress in neuro-psychopharmacology & biological psychiatry},
volume = {149},
number = {},
pages = {111834},
doi = {10.1016/j.pnpbp.2026.111834},
pmid = {42508631},
issn = {1878-4216},
abstract = {Heat shock protein 90 (HSP90) is a central regulator of cellular proteostasis, coordinating the folding, stabilization, and turnover of a wide range of client proteins in the cytosol, endoplasmic reticulum, and mitochondria. Accumulating evidence indicates that the four HSP90 paralogs HSP90α, HSP90β, GRP94, and TRAP1 have distinct pathological roles in neurodegenerative and metabolic diseases. In neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, aberrant HSP90 activity contributes to the persistence of toxic protein conformers, defective autophagy, mitochondrial dysfunction, and chronic neuroinflammation. In metabolic disorders such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease, GRP94- and TRAP1-dependent signaling promotes endoplasmic reticulum stress, impaired mitochondrial metabolism, insulin resistance, and inflammatory remodeling. These mechanistic insights have accelerated the development of a new generation of HSP90 inhibitors with improved selectivity, tissue targeting, and brain penetration. Unlike earlier pan-HSP90 inhibitors, these compounds are designed to exploit paralog-specific vulnerabilities and may enable safer long-term modulation of disease-relevant chaperone networks. This review summarizes current advances in the biology and pharmacology of HSP90 paralogs and proposes isoform-selective HSP90 targeting as a promising therapeutic strategy at the intersection of neurodegeneration and metabolic dysfunction.},
}

@article {pmid42510722,
year = {2026},
author = {Avitabile, A and Rusciano, D and Amato, R and Cannizzaro, L and Gagliano, C},
title = {Sex-Dependent Brain Plasticity in Neurological Disease: From Biological Variability to Adaptive, Compensatory, and Maladaptive Trajectories.},
journal = {Biology},
volume = {15},
number = {14},
pages = {},
doi = {10.3390/biology15141176},
pmid = {42510722},
issn = {2079-7737},
abstract = {Brain plasticity is often described as the capacity of the nervous system to change in response to development, experience, injury, disease, or treatment. That definition is useful, but it can obscure two clinically important points: plasticity is biologically constrained, and change is not always beneficial. This narrative review examines sex-dependent brain plasticity as a context-sensitive process rather than as a simple male-female contrast. We distinguish four operational outcomes of plasticity: (i) reparative plasticity, which restores structure or function; (ii) compensatory plasticity, which preserves performance through alternative or more costly strategies; (iii) insufficient plasticity, in which reorganization is too weak or unstable to sustain function; and (iv) maladaptive plasticity, in which plastic change reinforces dysfunction, pain, excitability, rigidity, or decline. We also define adaptive reserve as the integrated capacity of neural, glial, vascular, immune, metabolic, endocrine, and gene-regulatory systems to support useful reorganization under stress. The review evaluates endocrine, synaptic, neuroimmune, mitochondrial, vascular, stress-related, and epigenetic mechanisms, indicating where evidence for sex-dependent effects is relatively strong and where it remains indirect, inconsistent, or context-dependent. Disease examples include autism spectrum disorder, attention-deficit/hyperactivity disorder, epilepsy, intellectual disability, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, traumatic and ischemic injury, multiple sclerosis, chronic pain, aging, and systemic metabolic or inflammatory disorders. Throughout, biological sex is separated from gender-related social, diagnostic, and health-care determinants. We conclude that therapeutic strategies should not aim simply to enhance plasticity, but to guide it by matching intervention, timing, dose, biological readiness, and monitoring to the patient's adaptive state.},
}

@article {pmid42511587,
year = {2026},
author = {Korošec, T and Rogelj, B and Župunski, V},
title = {LINE-1 Retrotransposons and Amyotrophic Lateral Sclerosis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {14},
pages = {},
pmid = {42511587},
issn = {1422-0067},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons. While monogenic causes account for a minority of cases, in most cases, ALS is sporadic and likely arises from multilayer interactions of genetic architecture, aging-associated loss of genome regulation, and inflammatory stress. Long interspersed nuclear element-1 (LINE-1) retrotransposons are endogenous mobile elements that are tightly controlled through various cellular mechanisms under normal conditions. When abnormally active, they are involved in gene inactivation, expression regulation, and genomic instability, leading to cellular processes such as innate immunity and cell death. Here, we present mechanistic links between LINE-1 and ALS. These include evidence that the burden of retrotransposition-competent LINE-1s (RC-L1s) is increased in ALS genomes, positioning RC-L1 load as a candidate contributor to missing heritability in sporadic disease. We also integrate emerging data showing that LINE-1 RNA can be intrinsically toxic independently of new insertions, as it promotes chromatin opening and transcriptional epigenetic noise, particularly when nuclear RNA surveillance pathways fail in TDP-43 pathology. Finally, we review how LINE-1-derived DNA/RNA intermediates can engage innate immune sensors, highlighting the cGAS-STING axis as a plausible route from LINE-1 de-repression to neuroinflammation. Together, these concepts support a model in which genetic RC-L1 load and age-/pathology-driven LINE-1 de-repression converge on nuclear dysfunction and inflammatory amplification, suggesting concrete molecular nodes for therapeutic intervention.},
}

@article {pmid42511680,
year = {2026},
author = {Podshivalova, ES and Kutsev, SI and Shestopalov, AV},
title = {The Kynurenine Pathway: Unraveling Its Role in Neurological Disorders via Mammalian Cellular Models.},
journal = {International journal of molecular sciences},
volume = {27},
number = {14},
pages = {},
pmid = {42511680},
issn = {1422-0067},
abstract = {The kynurenine pathway (KP) constitutes the primary route of tryptophan catabolism, generating a spectrum of neuroactive metabolites that profoundly influence central nervous system function. Dysregulation of the KP is increasingly recognized as a critical pathogenic mechanism underlying diverse neuropathological conditions. This review critically evaluates the most widely cited mammalian cellular models currently utilized to delineate the causal role of KP alterations in neurological disease. Specifically, this article examines primary cell cultures, immortalized and tumor-derived cell lines, stem cell-derived systems, and ex vivo organotypic brain slices and tissues, highlighting their distinct methodological advantages, translational limitations, and specific enzymatic profiles. Across the described cellular systems, a recurring mechanistic theme emerges: quinolinic acid-driven mitochondrial dysfunction, oxidative stress, and NAD+ depletion converge in neurodegenerative conditions such as Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Conversely, kynurenic acid exhibits disorder-dependent-and at times opposing-roles, attenuating dopaminergic neurotoxicity in Parkinson's disease models while contributing to synaptic pruning deficits in schizophrenia models. Furthermore, cellular models demonstrate that IDO1/TDO induction and downstream metabolite shifts are frequently cell type- and species-dependent, complicating direct extrapolation to human pathology. Because no single experimental system achieves complete physiological fidelity, elucidating the complex dynamics of the KP and identifying novel therapeutic targets requires the integration of data across complementary platforms.},
}

@article {pmid42512450,
year = {2026},
author = {Yogi, S and Singh, A},
title = {Molecular Mechanisms of Neurodegenerative Diseases: Emerging Biomarkers and Therapeutic Targets.},
journal = {Brain sciences},
volume = {16},
number = {7},
pages = {},
doi = {10.3390/brainsci16070675},
pmid = {42512450},
issn = {2076-3425},
abstract = {Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), involve the gradual loss of structure or function of neurons in the nervous system and are an increasing threat to the aging population worldwide. Although these disorders have different clinical features which affect cognition, movement and other vital body functions, they share key underlying molecular and cellular processes. This starts with protein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, dysregulated protein homeostasis, neuroinflammation, and disrupted cell death pathways. Recent findings have added disease-specific processes, like amyloid-β and tau aggregates in AD, α-synuclein aggregation and mitophagy failure in PD's, TDP-43-related impaired RNA metabolism in ALS, and mutant huntingtin causing transcription aberrations in HD. Protein interactome network analysis showed mechanistic crosstalk between pathogenic proteins of AD and PD. New evidence highlights how lysosomal dysfunction, endoplasmic reticulum stress, and microglial activation, act as a common axis in neurodegeneration. Advancements in genomics and epigenomics have found shared genetic risk loci and regulatory processes that affect how diseases develop and progress. Simultaneously, new biomarkers like circulating microRNAs, exosome-related pathological proteins, neurofilament light chain, inflammatory cytokines, and microglial activation markers are powering early diagnosis tools and disease variations. New imaging techniques also allow for the identification of protein aggregations before symptoms appear. Overall, these findings are accelerating targeted treatments and personalized medicine aimed at disease progression. This review highlights current insights into the molecular mechanisms of NDs and discusses new biomarkers and treatment targets that help future diagnostic and treatment strategies.},
}

@article {pmid42512540,
year = {2026},
author = {Manzo, J and Hernández-Aguilar, ME},
title = {Autism and Neurodegeneration: Distinct Disorders or a Shared Biological Continuum?.},
journal = {Brain sciences},
volume = {16},
number = {7},
pages = {},
doi = {10.3390/brainsci16070766},
pmid = {42512540},
issn = {2076-3425},
abstract = {BACKGROUND/OBJECTIVES: Autism spectrum disorder (ASD) is traditionally classified as a neurodevelopmental condition, whereas neurodegenerative diseases are defined by progressive neuronal decline in later life. This separation has shaped research and clinical practice, yet emerging evidence suggests potential biological overlap. This review aims to evaluate whether ASD and neurodegenerative disorders represent distinct entities or are linked through shared mechanisms operating across the lifespan.

METHODS: This narrative review synthesizes findings from genetic, molecular, cellular, circuit-level, and epidemiological studies examining ASD and major neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. Emphasis is placed on identifying convergent pathways and evaluating evidence within a lifespan-oriented framework.

RESULTS: Across multiple levels of analysis, ASD and neurodegenerative diseases share partially overlapping biological mechanisms, including mitochondrial dysfunction, impaired proteostasis, neuroimmune alterations, and network-level instability. Genetic and molecular data reveal pleiotropic pathways influencing both early neurodevelopment and later neuronal resilience. Circuit-level studies highlight shared principles of network vulnerability, including cerebellar involvement and excitation-inhibition imbalance. Epidemiological data further indicate increased risk of dementia and parkinsonian features in autistic adults. These convergences suggest that early neurodevelopmental alterations may establish latent vulnerabilities that, under specific conditions, intersect with neurodegenerative processes later in life.

CONCLUSIONS: ASD and neurodegenerative diseases are best understood as distinct clinical conditions that share partially overlapping biological substrates. Rather than implying a deterministic progression, the evidence supports a model of lifespan convergence in which timing, context, and individual susceptibility shape outcomes. This framework highlights the need for integrated research and clinical approaches that consider brain health as a continuous process from development through aging.},
}

@article {pmid42498430,
year = {2026},
author = {Desai, KM and Thakkar, MD and Somaiya, TS and Thomas, DC},
title = {Neurodegenerative Diseases and Sleep Disorders: The Bidirectional Relationship.},
journal = {The Medical clinics of North America},
volume = {110},
number = {5},
pages = {889-905},
doi = {10.1016/j.mcna.2025.12.001},
pmid = {42498430},
issn = {1557-9859},
mesh = {Humans ; *Sleep Wake Disorders/diagnosis/complications/etiology/therapy/physiopathology ; *Neurodegenerative Diseases/complications/diagnosis/physiopathology ; Parkinson Disease/complications ; },
abstract = {Neurodegeneration is mostly irreversible and progressive. Neurodegenerative diseases (NDDs) represent a large group of disorders that have varied clinical and pathologic representations. These include Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis, among others. A common factor in all these NDDs is sleep disorders (SDs). NDDs and SDs are bidirectional. Screening for SDs should be an integral part of a workup of NDDs. Management of one can improve the prognosis of the other.},
}

Humans
*Sleep Wake Disorders/diagnosis/complications/etiology/therapy/physiopathology
*Neurodegenerative Diseases/complications/diagnosis/physiopathology
Parkinson Disease/complications

@article {pmid42504602,
year = {2026},
author = {Eisen, A and Durham, HD and Pioro, E},
title = {The aging brain that doesn't fail: how neural resilience masks neurodegeneration.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/21678421.2026.2705693},
pmid = {42504602},
issn = {2167-9223},
abstract = {Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease are usually framed as consequences of aging-related pathogenic processes, including impaired proteostasis with protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Yet, most individuals, even into advanced age, do not develop clinically significant neurodegenerative disease. This discrepancy suggests that the nervous system possesses robust and redundant protective mechanisms that maintain neural integrity despite cumulative molecular and cellular stress. In this perspective, we propose that neurodegenerative diseases arise not simply from the presence of pathogenic processes, but when integrated resilience systems fail to maintain homeostasis or when reserve mechanisms no longer compensate for accumulated pathology. We have synthesized a threshold-based model of disease emergence based on evidence across proteostasis, mitochondrial function, neuroimmune regulation, glial biology, network-level compensation, and barrier integrity, while integrating genetic, environmental, developmental, and stochastic modifiers. We distinguish biological resilience, which actively limits or repairs pathology, from reserve, which permits function despite pathology. We further propose that clinical disease emerges only when age-related cumulative stress exceeds the combined capacity of resilience and reserve. Reframing neurodegeneration as a failure of preservation systems offers new directions for prevention and therapeutic development.},
}

@article {pmid42505348,
year = {2026},
author = {Liu, B and Zhang, L and Lv, B and Xu, C and Han, L and Yan, Q and Wang, X},
title = {Copper Homeostasis and Cuproptosis in Neurodegenerative Diseases.},
journal = {Cells},
volume = {15},
number = {14},
pages = {},
doi = {10.3390/cells15141238},
pmid = {42505348},
issn = {2073-4409},
mesh = {Humans ; *Copper/metabolism ; *Cuproptosis ; *Homeostasis ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Mitochondria/metabolism ; Proteotoxic Stress ; },
abstract = {Copper is an essential trace element required for numerous enzymatic processes in the brain, including mitochondrial metabolism, antioxidant defense, and gene expression regulation. Recent studies have further implicated copper in a newly defined form of regulated cell death termed cuproptosis, providing a mechanistic framework for copper-dependent cytotoxicity. Increasing evidence indicates that copper dyshomeostasis is a common feature of major neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), where it is associated with protein misfolding, redox imbalance, and neuronal vulnerability. Nevertheless, the mechanistic link between copper dysregulation and neuronal cell death remains incompletely defined. In this review, we systematically summarize the molecular mechanisms governing copper homeostasis and intracellular copper trafficking, while providing a timely, updated, and in-depth overview of the mechanistic basis and emerging biology of cuproptosis. We further comprehensively evaluate the current evidence linking copper dysregulation and cuproptosis-related pathways to neurodegenerative diseases, with particular emphasis on distinguishing mechanistic causation from pathological correlation. Importantly, we discuss current therapeutic strategies and emerging clinical efforts targeting copper metabolism, while highlighting the major challenges in defining the pathological significance and mechanistic contribution of cuproptosis in neurodegenerative diseases. Collectively, this review provides an updated framework for understanding the pathological significance and translational potential of cuproptosis in neurodegenerative diseases.},
}

Humans
*Copper/metabolism
*Cuproptosis
*Homeostasis
*Neurodegenerative Diseases/metabolism/pathology
Animals
Mitochondria/metabolism
Proteotoxic Stress

@article {pmid42508391,
year = {2026},
author = {Gao, W and Lee, HY and Min, KJ},
title = {Aging-Related Metaflammation and Mitochondrial Dysfunction in Neurodegenerative Diseases.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2026.0366},
pmid = {42508391},
issn = {2152-5250},
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are increasingly recognized as manifestations of aging-associated systemic dysfunction, rather than isolated brain disorders. Central to this dysfunction is the interplay among metaflammation, mitochondrial breakdown, and chronic neuroinflammation. Metaflammation, driven by peripheral metabolic stress, may prime the brain's immune environment through cytokine signaling and blood-brain barrier compromise. This metabolic-inflammatory crosstalk is thought to impair mitochondrial integrity in neurons and glial cells, promoting oxidative stress and the release of pro-inflammatory mitochondrial components. These mitochondrial signals, in turn, may activate microglial and astrocytic innate immune responses, creating a potentially self-reinforcing cycle of neuroinflammation and energy failure that may contribute to neuronal loss. This review outlines a proposed framework linking metaflammation to neurodegeneration, emphasizing shared mechanisms across AD, PD, and ALS. We further examine preclinical and clinical advances in therapeutic strategies that target this axis including anti-inflammatory agents, caloric restriction, mitophagy enhancers, mitochondrial antioxidants, and senescence-targeted therapies. Together, these interventions reflect a shift from symptom management to systemic metabolic and immune modulation, offering a unified framework for understanding and potentially influencing age-related neurodegeneration.},
}

@article {pmid42508540,
year = {2026},
author = {Sun, R and Duan, X and Wang, X and Liu, J and Li, Z and Wang, Y},
title = {R-loops: Biological Functions, Regulatory Mechanisms, and Therapeutic Implications in Brain Diseases-A Review.},
journal = {Molecular and cellular probes},
volume = {},
number = {},
pages = {102081},
doi = {10.1016/j.mcp.2026.102081},
pmid = {42508540},
issn = {1096-1194},
abstract = {BACKGROUND: R-loops are three-stranded nucleic acid structures formed by a DNA-RNA hybrid and a displaced single-stranded DNA. They regulate transcription, replication, and DNA repair, but their dysregulation causes genomic instability and inflammation, contributing to brain diseases. The nervous system exhibits selective vulnerability to R-loop stress due to ultra-long gene transcription, post-mitotic longevity, and high metabolic demands.

METHODS: This review synthesizes current literature from PubMed, Scopus, Web of Science, and Embase (2010-2026) on R-loop biology, with a focus on brain-specific mechanisms, regulatory factors (SETX, ZPR1, METTL3, TDP-43/FUS), and disease models.

RESULTS: In neurodegeneration, R-loop accumulation drives repeat expansion disorders (Fragile X, Huntington's disease) and loss-of-function SETX mutations (AOA2), whereas gain-of-function SETX (L389S) causes pathological R-loop depletion in ALS4, disrupting TGF-β signaling. TDP-43/FUS and SMN are integral to R-loop resolution, unifying ALS/FTD and SMA. In brain cancers, METTL3-mediated m[6]A modification of TERRA stabilizes telomeric R-loops in ALT-positive neuroblastoma, creating a therapeutic vulnerability to METTL3 inhibitors (STM2457, STC-15). Glioma stem cells rely on m[6]A-modified circPOLR2B to regulate R-loop formation and malignancy. Clinical-stage agents (EP102, TUG1ASO, ATX-559) and R-loop-derived prognostic signatures (RLPI) are emerging, but translation is hindered by a lack of non-invasive biomarkers and the dual physiological/pathological roles of R-loops.

CONCLUSIONS: R-loops are central to brain disease pathogenesis, offering promising therapeutic targets. Future research should prioritize precision R-loop modulators, non-invasive biomarkers, and combinatorial strategies.},
}

@article {pmid41178766,
year = {2026},
author = {Wang, Y and Hu, J and Zhu, Q and Wang, S and Yu, S},
title = {Emerging Potential of Ras-proximate-1 (Rap1) in Mediating Neurodegenerative Diseases.},
journal = {Current neuropharmacology},
volume = {24},
number = {6},
pages = {804-816},
pmid = {41178766},
issn = {1875-6190},
mesh = {Humans ; Animals ; *Neurodegenerative Diseases/metabolism ; *rap1 GTP-Binding Proteins/metabolism ; Signal Transduction/physiology ; },
abstract = {Neurodegenerative diseases have posed a rising global threat to the aging population, presenting structural and functional impairments in the central nervous system. These progressive disorders, which affect the brain and spinal cord, develop due to the continuous loss of neurons and myelin sheaths. Such specific pathophysiological changes lead to neurological dysfunction in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, resulting in typical motor dysfunctions and cognitive disorders, as well as symptoms like behavioral abnormalities and personality changes. To date, despite various treatments attempting to manage these symptoms, patients' quality of life remains severely deteriorated. A few effective therapeutics are available to mitigate the progression of neurodegenerative injuries. Increasing attention is now focused on molecular regulatory mechanisms, particularly the association between immune regulation and the neurovascular unit. A critical component in this process is Ras-proximate-1 (Rap1), a small Guanosine Triphosphatase (GTPase). Rap1 is determined to regulate glia-mediated immunoinflammatory responses, vascular endothelial function, and neuronal activity. It also modulates synaptic plasticity and mitochondrial function via autophagy-dependent modulation, which are significantly impacted during neuronal degeneration. Additionally, signaling pathways, including PI3K/Akt and ERK, are identified as its downstream effectors. Furthermore, by mediating the permeability of the blood-brain barrier, Rap1 probably influences neuroimmune-vascular modulation throughout the development of neurological disorders. In this review, we investigate recent studies to explore the emerging therapeutic potential of Rap1 in the inflammation-related regulation within neurodegenerative diseases. We also discuss novel treatments and possible targets, including natural medicines and genetic modulation, to enhance therapeutic effects and improve prognosis.},
}

Humans
Animals
*Neurodegenerative Diseases/metabolism
*rap1 GTP-Binding Proteins/metabolism
Signal Transduction/physiology

@article {pmid42491041,
year = {2026},
author = {Wei, Z and Bai, L and Liu, X and Zhou, Y and Zheng, L and Zhang, B and Wang, L and Zou, W},
title = {Histone lactylation-mediated glycolysis-ferroptosis axis in neurological diseases.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1820758},
pmid = {42491041},
issn = {1662-5099},
abstract = {Histone lactylation is an emerging epigenetic modification that covalently links the glycolytic metabolite lactate to histones, thereby establishing a direct link between cellular metabolic status and gene transcription programs. Recent studies have shown that this modification plays a key role in regulating cellular sensitivity to ferroptosis, forming a novel regulatory axis of "glycolysis-lactylation-ferroptosis." This article systematically reviews the biological functions of histone lactylation in the nervous system, with a focus on elucidating how it participates in the pathological processes of various neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), cerebral stroke, and amyotrophic lateral sclerosis (ALS), by regulating the expression of ferroptosis-related genes. The article integrates the latest research on molecular mechanisms, explores the value of this regulatory axis as a potential biomarker for disease diagnosis and a therapeutic target, and provides an outlook on future research directions in this field.},
}

@article {pmid42497626,
year = {2026},
author = {Lee, JY and Hong, S and Kim, E},
title = {Soft skills education and training across the nursing continuum: A scoping review.},
journal = {Nurse education today},
volume = {166},
number = {},
pages = {107287},
doi = {10.1016/j.nedt.2026.107287},
pmid = {42497626},
issn = {1532-2793},
abstract = {AIMS: Soft skills are essential for safe and effective nursing practice, supporting communication, collaboration, and professional judgment in complex care settings. Despite their importance, new graduate nurses often struggle with core soft skills, highlighting a persistent gap between education and clinical demands. This scoping review maps current evidence on soft skills education and training for nursing students and nurses, focusing on core concepts, teaching approaches, and evaluation methods.

DESIGN: This scoping review was conducted following the PRISMA Scoping Review guidelines.

DATA SOURCES: Five databases-MEDLINE, CINAHL, Embase, Cochrane Library, and PsycINFO-were searched for studies published 2015-2025.

REVIEW METHODS: Eligible studies used experimental designs to deliver soft skill-focused education or training to nursing students or nurses. Data extraction followed the TIDieR checklist, and soft skills were classified using an adapted version of Song et al.'s framework.

RESULTS: Twenty-four studies met the inclusion criteria; most involved nursing students and quasi-experimental designs. Effective Interaction and Professionalism were the most frequently addressed skill domains. Student-focused programs emphasized interpersonal and cognitive skills, whereas nurse programs concentrated on preparedness, work management, and teamwork. Traditional lectures predominated, while participatory and emerging approaches such as virtual reality, escape rooms, and game-based learning were less common. Nurse training was typically single-session, whereas student programs were more longitudinal. Most studies relied on self-report measures and included limited follow-up.

CONCLUSIONS: A distinctive pattern emerged between students and nurses, suggesting that student-focused programs tend to emphasize foundational interpersonal skills while nurse-focused interventions are more likely to address clinically integrated competencies. This gap underscores the need to better align nursing curricula with real-world competency requirements. Educational programs on soft skills should incorporate active, learner-centered teaching strategies, rigorous evaluation methods with long-term follow-up, and validated assessment tools to better prepare nurses for contemporary healthcare demands.},
}

@article {pmid42484672,
year = {2026},
author = {Shen, Z and Yu, Q},
title = {Protein arginine methyltransferases as regulators of phase separation: implications in cancer and neurodegenerative diseases.},
journal = {European biophysics journal : EBJ},
volume = {},
number = {},
pages = {},
pmid = {42484672},
issn = {1432-1017},
abstract = {Protein arginine methyltransferases (PRMTs) catalyze arginine methylation, a key post-translational modification (PTM) regulating chromatin organization, RNA metabolism, and signaling. Recent studies reveal that PRMT-mediated methylation also modulates liquid-liquid phase separation (LLPS), which organizes membraneless condensates controlling transcription, stress response, and genome stability. Dysregulated PRMT activity disrupts condensate dynamics, contributing to cancer and neurodegenerative diseases. In cancer, PRMT1, PRMT5, and PRMT6 promote tumor progression via methylation-dependent condensates that enhance oncogenic transcription and stress resistance. In the nervous system, PRMT1, PRMT4, PRMT5, PRMT6, and PRMT8 regulate LLPS of proteins, linking aberrant methylation to ALS and Huntington's disease. This review highlights PRMTs as key modulators of phase separation and potential therapeutic targets in both oncology and neurodegeneration.},
}

@article {pmid42487057,
year = {2026},
author = {Adams, J},
title = {"Hermeneutic burden" and clinical responsibility: a response to Sparrow et al. on explanation and machine learning.},
journal = {Monash bioethics review},
volume = {},
number = {},
pages = {},
pmid = {42487057},
issn = {1836-6716},
abstract = {This paper critically reviews Sparrow et al.'s notion of the "hermeneutic burden" placed upon clinicians by the demand for explainable artificial intelligence (XAI) in the context of adaptive machine learning (ML) systems. While Sparrow et al. highlight important additional labour that may be required of clinicians, this response argues that framing explanation primarily in terms of such a burden obscures its overall ethical significance. This paper therefore offers a supplementary account of the interpretive work associated with XAI in medicine that places it within existing models of the patient-clinician relationship. In particular, Emanuel and Emanuel's influential typology consisting of four models of the patient-physician relationship is used to extract possible justifications for the responsibility to grasp and explain not only patients' values and conditions but also ML outputs. This allows us to distinguish between 'hermeneutic burden' and 'hermeneutic responsibility' and emphasise that explanation in medicine is not an incidental task but part of a clinician's professional role, particularly on 'interpretive' and 'deliberative' models. The paper thus argues that viewing explanation as a hermeneutic responsibility linked to patient autonomy clarifies the ethical significance of XAI in terms of both the grounds and scope of clinicians' responsibilities. At its core, the ethical challenge raised by XAI in clinical practice concerns not only the burdens it may impose on clinicians but also the evolution of clinicians' traditional interpretive duties in the novel context of ML-mediated care.},
}

@article {pmid42489904,
year = {2026},
author = {Jellinger, KA},
title = {Psychiatric disorders in amyotrophic lateral sclerosis: a short note.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42489904},
issn = {1435-1463},
abstract = {Traditionally, amyotrophic lateral sclerosis (ALS) has been defined as a rapidly progressive neurodegenerative disorder that affects the large motor neurons of the brain and spinal cord. The assumption that ALS is a pure motor disorder has been increasingly challenged by accumulating evidence about an association between ALS and psychiatric disorders. They often precede the onset of motor symptoms or psychoses; hallucinations and schizophrenia may occur as concomitant changes. These non-motor disorders have a close relationship with disease onset or may be related to a larger framework of neuronal network disruptions in motor neuron disorders. The link between ALS and schizophrenia was supported by substantial genetic correlations associating the C9orf72 gene expansion with psychiatric disorders. The genetic correlation between ALS and schizophrenia was estimated to be 14.3% with frequent polygenic risk scores. Increased psychotic symptoms in C9orf72 carriers correlate with atrophy in a distributed cortical and subcortical network that includes multiple cerebral regions. ALS kindreds often present higher rates of psychiatric illnesses, and early schizophrenia is significantly associated with the development of ALS. Further studies should attempt to delineate the risk of psychiatric disorders in C9orf72 kindreds to aid in clinical decision making and genetic counseling, through collaborations between neurology and psychiatry.},
}

@article {pmid41361897,
year = {2026},
author = {Rosenfeld, J and Abrahams, S and McHutchinson, C and Ajroud-Driss, S and Weber, M and Paganoni, S and Mitsumoto, H and Genge, A and Grosskreutz, J and Van Den Berg, L and Andrews, J and Kiernan, MC},
title = {Utility of patient subgrouping in ALS clinical trials: a World Federation of Neurology white paper.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {27},
number = {5-6},
pages = {493-500},
doi = {10.1080/21678421.2025.2593308},
pmid = {41361897},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/classification/diagnosis ; *Clinical Trials as Topic/methods ; *Neurology/standards ; *Societies, Medical/standards ; },
abstract = {The heterogeneity among the amyotrophic lateral sclerosis (ALS)/MND patient population is well recognized but not well understood. Such heterogeneity may represent a significant confound in our current and prior clinical trials as certain subgroups of patients might have a selective response (or resistance) to a novel therapeutic. The basis on which to segregate the patient population is, however, unclear. The ALS/MND Committee of the World Federation of Neurology (WFN) convened a symposium to discuss various strategies that might be considered for separating (stratifying) the population to further study. The results of that conference are presented here as a white paper, reflecting current understanding of several of the various criteria that could be implemented to divide the patient population as presented and discussed at that meeting. Consideration of grouping patients based on phenotype, cognitive involvement, imaging, or electrophysiology is presented here.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/classification/diagnosis
*Clinical Trials as Topic/methods
*Neurology/standards
*Societies, Medical/standards

@article {pmid41843813,
year = {2026},
author = {Meyer, T and Ticozzi, N and Weber, M and Ravits, J and Lingor, P and Kuźma-Kozakiewicz, M and Boentert, M and Grehl, T and Corcia, P and Povedano Panadés, M and Maier, A and Ingre, C and Cetin, H and Weydt, P and Lunetta, C and van den Berg, L and Ludolph, AC and Brenner, D and Turner, MR and Genge, A},
title = {ALS motor phenotypes: a revised 'OPM' classification.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {27},
number = {5-6},
pages = {540-552},
doi = {10.1080/21678421.2026.2644277},
pmid = {41843813},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/classification/diagnosis ; *Phenotype ; *Motor Neurons/physiology ; },
abstract = {BACKGROUND: Defining motor phenotypes in amyotrophic lateral sclerosis (ALS) is important for individualized care and optimal therapeutic trial design. The "ALS-OPM" classification is based on the onset region (O), the propagation of motor symptoms (P), and the degree of clinical upper (UMN) and/or lower (LMN) motor neuron dysfunction (M).

METHODS: An international ALS expert focus group was held in September 2025, followed by a consensus process through which revisions of the OPM classification were finalized.

RESULTS: Onset (O1-4) identifies first motor symptoms as relating to the head (O1), distal/proximal arm (O2d/p), respiratory/axial trunk (O3r/a), or distal/proximal leg (O4d/p). Onset symptoms are defined by weakness or slowed, poorly coordinated voluntary movements in the muscles of the head, arm, trunk, or leg, including dysarthria, dysphagia, dysphonia, dyspnea, and axial instability. Propagation (P1(n)) or absence of propagation (P0(n)) of motor symptoms from the onset region to another body region are designated, where n denotes the number of months from onset to propagation or assessment. The degree of UMN dysfunction (slowed, poorly coordinated voluntary movements, hyperreflexia and/or spastic muscle tone, emotional lability) and/or LMN dysfunction (weakness with associated muscle atrophy) is classified as follows: balanced UMN and LMN dysfunction (M0); dominant (M1d) or pure UMN dysfunction (M1p); dominant (M2d) or pure LMN dysfunction (M2p); and dissociated UMN/LMN dysfunction (M3), in which the arms and legs predominantly show LMN and UMN involvement, respectively.

CONCLUSION: The revised ALS-OPM classification aims to make it routine, practical and feasible to capture phenotype in clinical practice and therapeutic trials.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/classification/diagnosis
*Phenotype
*Motor Neurons/physiology

@article {pmid42060866,
year = {2026},
author = {Kiernan, MC and Genge, A and Grosskreutz, J and Kuwabara, S and Lillo, P and Rosenfeld, J and Cummings, C},
title = {The World Federation of Neurology Specialty Group in ALS/MND: toward strategic partnership and new frontiers.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {27},
number = {5-6},
pages = {501-503},
doi = {10.1080/21678421.2026.2663915},
pmid = {42060866},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis/epidemiology ; *Neurology/organization & administration ; *Societies, Medical ; *International Cooperation ; *Motor Neuron Disease/therapy/diagnosis/epidemiology ; },
abstract = {A memorandum of understanding was recently established between the World Federation of Neurology Specialty Group and the International Alliance of ALS/MND Associations. This new strategic partnership brings together leading clinicians and researchers with national and regional organizations dedicated to supporting ALS patients, their families, and caregivers. The purpose of partnership is to strengthen global coordination in research, education, advocacy, and clinical care for people living with MND. The agreement outlines shared priorities, including promoting equitable access to diagnosis and treatment, supporting capacity building in low- and middle-income regions, and facilitating the exchange of scientific knowledge and best practice. Both parties commit to joint initiatives such as international meetings, guideline development, clinical trials and data-sharing efforts that advance understanding of disease mechanisms and therapeutic approaches. Together, these organizations represent the scientific and human dimensions of the ALS challenge. Through partnership, the WFN Specialty Group and the International Alliance aim to accelerate progress toward improved outcomes and, ultimately, effective treatments for MND worldwide.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/diagnosis/epidemiology
*Neurology/organization & administration
*Societies, Medical
*International Cooperation
*Motor Neuron Disease/therapy/diagnosis/epidemiology

@article {pmid42476327,
year = {2026},
author = {Pattnaik, PP and Prusty, SK and Pati, S and Jew, KA and Bora, AK and Sahoo, J and Sahu, PK},
title = {Exploring shared genetic pathways and gene interplay in major neurodegenerative diseases: a comprehensive review.},
journal = {Gene},
volume = {1010},
number = {},
pages = {150318},
doi = {10.1016/j.gene.2026.150318},
pmid = {42476327},
issn = {1879-0038},
abstract = {Neurodegenerative diseases are progressive disorders that involve the loss and dysfunction of neurons. Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, Frontotemporal dementia are examples of diseases. While different clinically, these disorders have a common genetic, molecular and cellular basis. This review examines the common genetic pathways, along with the interactions between genes of major neurodegenerative diseases, with a focus on the key genes, such as APOE, SNCA, MAPT, TARDBP, LRRK2 and HTT. The common pathogenic mechanisms considered to play a major role in disease progression include protein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, neuroinflammation, diminished autophagy, and impaired lysosomal function, as well as synaptic degeneration. The review also emphasizes the role of systems biology strategies, such as genome-wide association studies, transcriptomics, proteomics, metabolomics, interactome analysis, and multi-omics integration, to unveiling complex molecular networks in neurodegeneration. Furthermore, the emerging biomarker strategies and therapeutic strategies targeting convergence signaling pathways including NF-κB, PI3K-Akt-mTOR, MAPK and Wnt/β-catenin are summarized. The common genetic basis and the cross-connecting molecular mechanisms of the various neurodegenerative diseases could help in the discovery of new biomarkers and pan-therapeutic targets. Further advances in molecular genetics, computational biology and precision medicine are needed to enhance early detection and the creation of effective disease-modifying treatments.},
}

@article {pmid42481875,
year = {2026},
author = {Sahin, U and Firat-Karalar, EN},
title = {The centrosome-cilium-centriolar satellite axis in neurodegenerative diseases.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {42481875},
issn = {1469-3178},
support = {101078097//EC | H2020 | PRIORITY 'Excellent science' | H2020 European Research Council (ERC)/ ; 3336//European Molecular Biology Organization (EMBO)/ ; 3622//European Molecular Biology Organization (EMBO)/ ; YIP//European Molecular Biology Organization (EMBO)/ ; (SU PREG)//Sabanci University President's Research/ ; },
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and hereditary ataxias, remain major global health challenges with limited therapeutic options. Although clinically and genetically diverse, these diseases share extensively studied cellular and molecular hallmarks, including protein aggregation, impaired proteostasis, cytoskeletal abnormalities, altered energy metabolism, nucleic acid damage, and chronic inflammation. Emerging evidence indicates that dysfunction of the centrosome-cilium-satellite axis intersects with these established pathways in disease- and cell type-specific contexts. This axis, composed of centrosomes, primary cilia, and centriolar satellites, coordinates cytoskeletal organization, ciliary signaling, trafficking, proteostasis, and stress responses and acquires specialized functions in neurons that support polarity, connectivity, and long-term maintenance. In this review, we outline the structure, function, and neuronal specializations of the centrosome-cilium-satellite axis, then examine how its dysfunction has been reported in neurodegenerative disease models. We also discuss centriolar satellites as regulators of centrosome and cilium biology whose disease-specific roles in classical NDDs remain comparatively underexplored, with insights from Huntington's disease and schizophrenia. Finally, we discuss therapeutic strategies aimed at restoring axis structure and dynamics, modulating ciliary signaling, and correcting disease-linked genetic or transcript-level defects, emphasizing mechanism-based approaches that require validation in disease-relevant models. Together, the centrosome-cilium-satellite axis provides an emerging framework for understanding context-dependent organelle dysfunction in neuronal vulnerability and neurodegeneration.},
}

@article {pmid41088992,
year = {2026},
author = {Essa, SM and Khosa, NA and Kakar, A and Ozturk, B and Ibrahim, IA and Haq, N},
title = {Unraveling the Potential of Stem Cell Therapy in Motor Neuron Disease: A Narrative Review.},
journal = {CNS & neurological disorders drug targets},
volume = {25},
number = {6},
pages = {403-415},
pmid = {41088992},
issn = {1996-3181},
mesh = {Humans ; *Motor Neuron Disease/therapy ; Animals ; *Stem Cell Transplantation/methods ; *Mesenchymal Stem Cell Transplantation/methods ; },
abstract = {Motor neuron disorders (MNDs), including ALS, are deadly neurodegenerative conditions that cause progressive motor neuron degeneration. With neuroprotection and the potential for neuron regeneration employing MSCs, ESCs, iPSCs, and NSCs, stem cell treatment presents a viable alternative to current medicines, which only control a limited number of symptoms. Following PRISMA criteria, this narrative review methodically screened 1248 records from the Cochrane, Web of Science, PubMed, and Scopus databases. Following a thorough screening process, 22 studies, including preclinical models and 19 clinical trials, were analysed to assess the therapeutic mechanisms, safety, and efficacy of stem cell therapies for MNDs. Mesenchymal stem cell (MSC) therapy has shown a promising safety profile and possible therapeutic efficacy in ALS, with no substantial transplant-related toxicity noted. ALS functional rating scale-revised (ALSFRS-R) scores and forced vital capacity (FVC) assessments from clinical trials, such as those evaluating autologous bone marrow-derived MSCs, demonstrated stabilisation in ALS development. Studies have also emphasised as to how immunomodulation and neurotrophic factors play a part in MSC-based therapies. Recent data indicate that repeated intrathecal MSC injection could extend the duration of therapeutic advantages. Clinical trials have shown safety and early efficacy signals for motor neurons produced from embryonic stem cells (ESCs), especially using AstroRx®. This suggests that ESCs could be a viable option for regenerative medicine. Nonetheless, issues, like host integration and differentiation optimisation, still exist. Although clinical translation is still in its early stages, induced pluripotent stem cells (iPSCs) and their derivatives provide disease modelling and patient-specific therapeutic applications. Stem cell therapy holds promise for treating MND, with MSCs leading the way in current trials. It is necessary to enhance ESC- and iPSC-based techniques to tackle integration issues. To ensure long-term safety and efficacy, therapies must be developed using standardised protocols, patient stratification, optimised delivery, and large-scale studies.},
}

Humans
*Motor Neuron Disease/therapy
Animals
*Stem Cell Transplantation/methods
*Mesenchymal Stem Cell Transplantation/methods

@article {pmid42471032,
year = {2026},
author = {Barrera-Chamorro, L and Gonzalez-de la Rosa, T and Arzalluz-Luque, J and Torrecillas-Lopez, M and Marquez-Paradas, E and Claro-Cala, CM and Navarro-Hortal, MD and Eichau, S and Garcia-Sanchez, MI and Montserrat-de la Paz, S},
title = {Sustainable next-generation prebiotics for brain health: microbiota-gut-brain axis in neurodegenerative and demyelinating diseases.},
journal = {Critical reviews in food science and nutrition},
volume = {},
number = {},
pages = {1-22},
doi = {10.1080/10408398.2026.2703335},
pmid = {42471032},
issn = {1549-7852},
abstract = {Neurodegenerative and neuroinflammatory diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, are increasingly associated with disruption of the microbiota-gut-brain axis. Common alterations include reduced beneficial microbial taxa, impaired short-chain fatty acid production, intestinal and blood-brain barrier dysfunction, and sustained inflammatory responses. These findings support the development of microbiota-targeted dietary interventions. This review summarizes current evidence on polyphenols, bioactive peptides, and pectin-derived oligosaccharides (POS) as prebiotic or prebiotic-like compounds with potential activity through the microbiota-gut-brain axis. Particular attention is given to structure-function relationships, host-microbe interactions, and the sustainable recovery of these compounds from food by-products. Preclinical studies suggest that these bioactives may reduce microglial activation, improve mitochondrial function, strengthen intestinal and blood-brain barrier integrity, and enhance cognitive or motor performance. Early clinical studies also indicate possible benefits on mood, selected cognitive outcomes, metabolic regulation, and inflammatory biomarkers, although evidence remains limited. Microbiota-derived metabolites from polyphenols, such as urolithins, together with glycomacropeptide and POS, appear to be key mediators. However, clinical validation in major neurodegenerative diseases remains fragmented. Standardized formulations, mechanistic trials, harmonized endpoints, and precision-nutrition strategies are required to confirm their therapeutic potential.},
}

@article {pmid42474734,
year = {2026},
author = {Zheng, Y and Bhalala, OG and Chin, KS and Watson, R and Yassi, N},
title = {Use of blood-based neurofilament light chain as an endpoint in clinical trials of neurodegenerative conditions: a scoping review.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42474734},
issn = {1432-1459},
mesh = {Humans ; *Neurofilament Proteins/blood ; *Neurodegenerative Diseases/blood/diagnosis ; Biomarkers/blood ; *Clinical Trials as Topic ; },
abstract = {INTRODUCTION: Neurofilament light chain (NfL) is a structural axonal protein measurable in CSF and blood, increasingly investigated as a biomarker of neuroaxonal injury in clinical and research contexts. This review aims to explore the use of blood-based NfL as an endpoint in clinical trials of neurodegenerative conditions.

METHOD: A database search of MEDLINE and EMBASE was conducted to identify interventional clinical trials and/or related post hoc analyses for neurodegenerative diseases, published between 2013 and 2024 that reported the use of serum or plasma NfL as an endpoint. Additional studies from reference lists of included trials were manually considered for inclusion where relevant. Data were charted descriptively by disease type and summarised.

RESULTS: 49 studies were included, 29 in multiple sclerosis (MS), eight in amyotrophic lateral sclerosis (ALS), six in Alzheimer's disease (AD), and six in other diseases. Across studies, reductions in NfL often paralleled improvements in primary efficacy outcomes, supporting its use as a biomarker of disease activity and treatment response. However, several studies demonstrated a lack of concordance between change in NfL and in clinical outcomes, some of which may be related to the non-disease-modifying mechanisms of the interventions studied. This necessitates careful consideration when applying blood-based NfL as a biomarker endpoint for studies involving such interventions.

CONCLUSION: Blood NfL is a promising biomarker with potential utility as a surrogate endpoint in neurological clinical trials, particularly for diseases with active axonal injury. Further validation, particularly around disease- and intervention-specific interpretation, is needed before blood NfL can be incorporated more routinely as a clinical endpoint.},
}

Humans
*Neurofilament Proteins/blood
*Neurodegenerative Diseases/blood/diagnosis
Biomarkers/blood
*Clinical Trials as Topic

@article {pmid42468901,
year = {2026},
author = {Halabian, N and Park, C and Omoto, L and Bocca, LF and Palacios, G and Wu, K and Hamani, C and Rabin, J and Abrahao, A and Davidson, B and Lipsman, N and Meng, Y},
title = {Focused ultrasound blood brain barrier opening for targeted therapeutics in neurodegenerative diseases.},
journal = {Biological psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.biopsych.2026.07.008},
pmid = {42468901},
issn = {1873-2402},
abstract = {Therapeutic focused ultrasound (FUS) leverages the non-invasive ultrasonic waves to modify the biological tissue. When administered alongside intravenous microbubbles, low-intensity FUS enables transient, targeted disruption of the blood-brain barrier (BBB), permitting passage of systemically administered therapeutics into the central nervous system (CNS) with high spatial precision. The ability to selectively modulate BBB permeability at the disease site has the potential to substantially expand the number of therapeutics that can be utilized in treating illnesses afflicting the CNS. Herein, we review the current applications of FUS for treating neurodegenerative disorders and diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). We discuss the research developments to date and future directions.},
}

@article {pmid42459525,
year = {2026},
author = {Majumdar, S and Samaiya, PK and Ahmed, S and Prajapati, SK},
title = {Imaging biomarkers in neurodegenerative diseases: advances and challenges.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1813588},
pmid = {42459525},
issn = {1663-4365},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), represent a major global health burden. Imaging biomarkers have emerged as important tools for improving the diagnosis, monitoring, and biological characterization of neurodegenerative diseases. Structural MRI, diffusion tensor imaging (DTI), functional MRI (fMRI), positron emission tomography (PET), hybrid PET/MRI and molecular imaging have transformed our ability to investigate neurodegeneration in vivo non-invasively. This review highlights updated information on how each imaging modality offers a unique window into different disease pathophysiology including regional atrophy, amyloid-β, tau, dopaminergic terminal degeneration, synaptic density (SV2A), and neuroinflammation. We also focused on the translational and evidence supporting biomarkers, appropriate use criteria for amyloid and tau PET imaging, and standardized quantification methods such as the Centiloid scale. The growing role of multimodal fusion, where imaging is increasingly integrated with scalable fluid biomarkers to enable "blood-first" strategies where high-risk patients are selectively referred to advanced imaging, improving feasibility and equity. Despite tremendous progress, there are still issues with their standardization, sensitivity, specificity, and clinical translation. Moreover, the review emphasizes the frontiers of α-synuclein and glial state-specific PET ligands, advanced diffusion models, and dynamic connectivity analysis to support precision medicine and mechanism-based trial design for NDDs.},
}

@article {pmid42459857,
year = {2026},
author = {Hu, M and You, L and Zhang, X and Xuan, Z and Ma, S and Wu, X},
title = {Experimental evidence of electroacupuncture in ALS mouse models: a systematic review and meta-analysis.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1780176},
pmid = {42459857},
issn = {1664-2295},
abstract = {OBJECTIVE: This study aimed to systematically evaluate the therapeutic efficacy of electroacupuncture (EA) in amyotrophic lateral sclerosis (ALS) and to elucidate the underlying neurobiological mechanisms by synthesizing preclinical evidence.

METHODS: According to the PICOS principle, relevant studies were searched in the following databases: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and CNKI. Search terms and strategies were determined based on MeSH terms. The methodological quality of the included studies was assessed using the SYRCLE's Risk of Bias tool and the CAMARADES checklist. Meta-analysis was performed using Stata 15.0 and Rstudio software.

RESULTS: Seventeen studies involving 372 animals were included. The quality scores of the included studies ranged from 5 to 8, with an average score of 7. The meta-analysis of the primary outcome, the rotarod test score, showed a significant improvement in the EA group compared to the control group [SMD = 3.31, 95% CI (2.05, 4.57), Z = 5.151, p < 0.001], indicating that EA can enhance motor function in ALS mice. Regarding secondary outcomes, EA intervention alleviated neuroinflammation, promoted neuronal survival, improved axonal regeneration inhibition, and stabilized RNA metabolism homeostasis. Consequently, it slowed disease progression, improved motor performance, prolonged survival time, and effectively protected motor neurons at the histopathological level (p < 0.05). These findings underscore the potential of EA as a promising multimodal therapeutic strategy for ALS. For the heterogeneity observed in the rotarod test, sensitivity analysis, subgroup analysis, and meta-regression did not identify its source. However, potential publication bias was detected, which might contribute to the heterogeneity. The heterogeneity for other outcome measures might originate from differences in stimulation parameters (e.g., waveform), acupoint selection, or treatment duration.

CONCLUSION: This meta-analysis demonstrates that EA confers significant neuroprotective benefits in preclinical ALS models, primarily through multi-target modulation of key pathological processes such as neuroinflammation, aberrant cell death signaling, and RNA metabolism. These preclinical findings underscore the potential of electroacupuncture as a complementary neuroprotective strategy and warrant further investigation in rigorous clinical trials.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251229183.},
}

@article {pmid42467162,
year = {2026},
author = {Barker-Jones, B and Navvuga, P and Baji, P and Marques, E and Hollingworth, W},
title = {Comparing User-Written Codes for Performing Economic Evaluations in Stata.},
journal = {PharmacoEconomics},
volume = {},
number = {},
pages = {},
pmid = {42467162},
issn = {1179-2027},
support = {RP-PG-0610-10048//National Institute for Health and Care Research/ ; PB-PG-0213-30021//National Institute for Health and Care Research/ ; },
abstract = {BACKGROUND: Several user-written Stata codes exist for trial-based economic evaluations, but they lack assessment and guidance. This study aimed to identify and compare publicly available user-written Stata codes for trial-based economic evaluations.

METHODS: A focused literature search of Ovid Medline, SSC Archive, The Stata Journal and Google Scholar was conducted to identify relevant codes to June 2025. Codes were applied to data from two clinical trials, both featuring missing data and covariate adjustment. Codes were compared in terms of their ability to estimate key economic parameters and produce graphical outputs and functionality in handling four common statistical challenges: correlated costs and effects, covariate adjustment, skewed costs and effects, and missing data.

RESULTS: We identified eight codes reported in four publications: codes for assessing health economic agreement (Gallacher et al.), sampling uncertainty for cost-effectiveness analysis (Glick et al.) and codes addressing missing data (Mutubuki et al. and Faria et al.). Gallacher et al.'s codes reported lower incremental quality-adjusted life years (QALYs) and net monetary benefit than Glick's et al.'s codes. Mutubuki et al. and Faria et al.'s codes produced comparable incremental costs and QALYs, though Faria et al. yielded wider confidence intervals in cost estimates.

DISCUSSION: Differences in estimates across statistical approaches show that code choice can influence economic evaluation results. Some codes were better suited for generating basic economic outputs, whereas others provide more comprehensive analyses or address specific statistical challenges including missing data. However, no single code provided all key outputs while addressing the main statistical challenges.},
}

@article {pmid42467293,
year = {2026},
author = {Hassan, MA and Al Amin, M and Sweilam, SH and Abohassan, M and Krishnan, K and Gupta, JK and Jahnavi, P and Vodeti, R and Radha, R and Gupta, PS and Reddy, KTK},
title = {Resveratrol and neuroprotection: modulation of cellular dynamics and signaling networks in neurodegenerative diseases.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42467293},
issn = {1568-5608},
abstract = {Progressive loss of neurons, oxidative stress, neuroinflammation, and mitochondrial dysfunction are hallmarks of neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Resveratrol, a polyphenolic phytoalexin mainly found in grapes and red wine, is a promising treatment candidate due to its diverse biological effects and neuroprotective properties. This review demonstrates the regulatory effects of resveratrol on cellular signaling pathways linked to NDs and its neuroprotective mechanisms. Resveratrol enhances neuronal survival, boosts mitochondrial biogenesis, and mitigates oxidative stress by affecting key molecular pathways, including SIRT1/AMPK, PI3K/Akt, MAPK, and Nrf2/ARE. The PI3K/Akt and ERK1/2 pathways promote neuronal regeneration by modulating pro-apoptotic and anti-apoptotic factors. Resveratrol inhibits NF-κB, reducing cytokine release and microglial activation, thereby exhibiting anti-inflammatory properties. It improves cognitive function, synaptic plasticity, and neuronal survival. Despite an increasing pharmacological profile, its practical applicability is limited by inadequate bioavailability, rapid metabolism, and restricted brain penetration. This review demonstrates resveratrol's effect on interconnected signaling networks related to neurodegeneration. We critically compare evidence from preclinical and clinical studies, demonstrating both therapeutic potential and translational limitations. Emerging nanotechnology-based delivery strategies are demonstrated to overcome bioavailability and blood-brain barrier penetration challenges. These insights provide a translational perspective for the future development of resveratrol-based interventions in NDs.},
}

@article {pmid42458453,
year = {2026},
author = {Bolsinger, MM and Vivek, N and Singh, J and Challa, A and Zhu, A and Rothell, T and Wang, S and Zhang, T and Zhu, S and Robbins, N and Fenwick, L and Ruttenberg, G and Bogoniewski, A and Taha, HB},
title = {Extracellular vesicles as a liquid biopsy for amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08562-8},
pmid = {42458453},
issn = {1479-5876},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative syndrome diagnosed clinically using standardized criteria, with neuropathological confirmation of motor neuron loss and TDP-43 aggregates in postmortem brain tissue. Extracellular vesicles (EVs) have emerged as potential minimally invasive biomarkers for ALS, but studies vary widely in methodology and reproducibility. We conducted a systematic review and meta-analysis to evaluate the diagnostic potential of EV-associated proteins and RNAs in ALS. Following PRISMA guidelines, we searched PubMed and EMBASE from inception to May 21st, 2026. Forty-one studies met inclusion criteria. Where published summary statistics were available, these were used directly; where they were not, data were reconstructed from figures or obtained from authors and re-analyzed to derive standardized effect sizes and exploratory diagnostic accuracy estimates. Random-effects models were used for continuous outcomes, and diagnostic accuracy was assessed using hierarchical summary ROC and bivariate random-effects models. Publication bias was evaluated using Begg, Egger, and funnel plots. EV-associated TDP-43 was the most frequently studied protein. Meta-analysis of five studies showed a moderate but non-significant increase in EVs from ALS vs. controls (SMD = 1.30) with high heterogeneity (I = 97.8%). Sixteen studies assessing EV-RNA biomarkers showed minimal overlap and limited independent replication. Diagnostic accuracy meta-analysis across 11 studies yielded moderate performance (AUC = 0.839). No publication bias was found across both meta-analyses. EV biomarkers for ALS show biological promise but are limited by methodological variability and insufficient replication. This work highlights the need for standardized protocols, transparent data sharing, and independent validation.},
}

@article {pmid42458498,
year = {2026},
author = {Wang, H and Wen, R and Parker, E and Yang, L},
title = {TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-026-03083-9},
pmid = {42458498},
issn = {1478-811X},
support = {32300959//National Natural Science Foundation of China/ ; SL2024A04J00578//Guangzhou Scientific Research Grant/ ; 22KJ04//SCNU Young Faculty Development Program/ ; },
abstract = {Triggering receptor expressed on myeloid cells 2 (TREM2) is a critical myeloid receptor expressed on the surface of central nervous system microglia, capable of integrating signals from lipids, damage-associated molecular patterns, and abnormal protein aggregates to regulate phagocytosis, metabolic adaptation, inflammatory remodeling, and pathology-associated responses. Accumulating evidence indicates that TREM2 is neither uniformly protective nor uniformly pathogenic; rather, its biological effects are highly context-dependent, governed collectively by disease stage, pathological substrates, cellular compartments, and the local microenvironment. By coupling with TYROBP/DAP12 or DAP10, TREM2 actively drives the state remodeling of pathology-associated microglia. It profoundly influences the onset and progression of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), as well as acute central nervous system injuries, including ischemic stroke, spinal cord injury (SCI), and traumatic brain injury (TBI). Concurrently, soluble TREM2 (sTREM2) holds significant potential not only as a biomarker but also as a context-dependent effector molecule actively participating in pathological regulation. This review synthesizes current advancements by focusing on four core themes: the structural and signaling logic of the TREM2 axis; its regulation of disease-associated microglia (DAM) remodeling; the cross-disease significance of sTREM2; and the mechanistic basis for the divergent outcomes observed with TREM2-targeted therapies across different experimental models and disease stages. The objective is to elucidate the context-dependent roles of TREM2 by analyzing consensus mechanisms, sources of discrepancy, and translational implications, thereby providing a theoretical framework and strategic direction for more precise TREM2-targeted interventions.},
}

@article {pmid41916622,
year = {2026},
author = {Addington, C and Davies, N and Howell, P and Cruickshank, S and Hainsworth, E},
title = {Lived experiences of cancer care for people living with HIV who are treated for anal cancer: a scoping review.},
journal = {BMJ open},
volume = {16},
number = {3},
pages = {e114180},
pmid = {41916622},
issn = {2044-6055},
mesh = {Humans ; *Anus Neoplasms/therapy/psychology/complications ; *HIV Infections/complications/psychology ; Quality of Life ; },
abstract = {OBJECTIVE: This scoping review aims to identify existing evidence on the lived experiences of people living with HIV and treated for anal cancer, and to identify what aspects of health and well-being are addressed in clinical guidance.

DESIGN: A preregistered protocol (Open Science Framework, 2025) guided the review. We followed the Arksey and O'Malley framework, incorporating Levac et al's refinements around stakeholder consultation. Joanna Briggs Institute (JBI) guidance informed eligibility and data for charting, and reporting adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

DATA SOURCES: Systematic searches were performed across multiple databases, including CINAHL, MEDLINE, PsycINFO and Embase, using EBSCOhost and Ovid, supplemented handsearching reference lists. Two search strategies were used: one for research studies and one for clinical guidelines.

ELIGIBILITY CRITERIA: Sources included people living with HIV treated for anal cancer, capturing lived experiences directly through qualitative studies or indirectly via quantitative patient-reported outcomes and/or health-related quality of life. Guidelines addressing HIV or anal cancer were also included.

DATA CHARTING AND SUMMARIES: Data were charted to capture patient experiences and outcomes on living with and beyond cancer, and how these are addressed in clinical management and guidance, including biomedical, psychosocial, sexual and functional aspects, and patient-reported outcomes.

RESULTS: Of 945 records, three studies and four guidelines met criteria. No study focused exclusively on people living with HIV; findings reflect broader anal cancer populations with HIV-positive subsets. Studies addressed aspects of health-related quality of life which we mapped into physical, psychosocial and sexual domains. Clinical guidance prioritised treatment dosage and survival, with limited attention to broader effects. Stakeholders highlighted that existing research and guidance miss important nuances of lived experience and care needs.

CONCLUSIONS: No identified research solely explored the lived experiences of people living with HIV treated for anal cancer, leaving guidance non-specific and biomedical. The identified domains offer a starting point for future research; however, to inform patient-centred care, stakeholders emphasised the need to understand how living with HIV and anal cancer shapes health needs.},
}

Humans
*Anus Neoplasms/therapy/psychology/complications
*HIV Infections/complications/psychology
Quality of Life

@article {pmid42442908,
year = {2026},
author = {Dongre, S and Soni, N and Bissa, B},
title = {Role of ESCRT pathway and autophagy in neurodegenerative diseases.},
journal = {International review of neurobiology},
volume = {187},
number = {},
pages = {1-16},
doi = {10.1016/bs.irn.2026.05.022},
pmid = {42442908},
issn = {2162-5514},
mesh = {Humans ; *Endosomal Sorting Complexes Required for Transport/metabolism ; *Autophagy/physiology ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; },
abstract = {Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss resulting from impaired proteostasis and vesicular trafficking. Neurons are particularly vulnerable to these processes due to their post-mitotic nature and complex architecture. Autophagy and the endolysosomal system constitute the primary degradative pathways responsible for maintaining neuronal homeostasis. However, increasing evidence indicates that their effective function critically depends on coordination with the endosomal sorting complexes required for transport (ESCRT). Beyond their canonical role in multivesicular body biogenesis and membrane scission, ESCRT components are now recognized as essential regulators of autophagosome closure, amphisome formation, autophagosome-lysosome fusion, and endolysosomal membrane repair. Disruption of this ESCRT-autophagy interface has emerged as a common pathological feature across major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis/frontotemporal dementia. This review synthesizes evidence from genetic, biochemical, and neuropathological studies to highlight shared molecular nodes, such as ESCRT-III components, the VPS4 ATPase, the adaptor protein ALIX, and late endosomal regulators, including Rab7, that couple membrane remodeling to autophagic flux. Failure of these regulatory checkpoints destabilizes endolysosomal integrity, arrests autophagic maturation, and promotes the accumulation of toxic protein species, thereby driving progressive neuronal degeneration. By framing neurodegeneration through the lens of ESCRT-autophagy coupling failure, this review provides a unified mechanistic perspective that links diverse pathogenic proteins to shared cellular vulnerabilities and identifies ESCRT-mediated membrane dynamics as a critical determinant of neuronal survival.},
}

Humans
*Endosomal Sorting Complexes Required for Transport/metabolism
*Autophagy/physiology
*Neurodegenerative Diseases/metabolism/pathology
Animals

@article {pmid42444959,
year = {2026},
author = {Akpa, B},
title = {The role of radiologic assessment in evaluating and monitoring respiratory function in amyotrophic lateral sclerosis (ALS) patients: a narrative review.},
journal = {Journal of thoracic disease},
volume = {18},
number = {6},
pages = {672},
pmid = {42444959},
issn = {2072-1439},
abstract = {BACKGROUND AND OBJECTIVE: Respiratory failure is the primary cause of mortality in amyotrophic lateral sclerosis (ALS), usually caused by progressive neuromuscular respiratory weakness. Standard pulmonary function tests (PFTs) such as maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and both supine and upright forced vital capacity (FVC) are crucial for objective measurements of diaphragmatic weakness but have limitations, including dependence on the patient's performance and the inability to detect early, subclinical diaphragmatic impairment or be used effectively in patients with bulbar symptoms. Radiological assessments, particularly dynamic imaging, have emerged as potential objective tools for evaluating respiratory function. This review comprehensively summarizes findings on the use of diaphragmatic ultrasound (DUS), dynamic chest magnetic resonance imaging (MRI) and deep learning (DL)-based chest computed tomography (CT) for assessing lung function in ALS patients.

METHODS: Key radiological metrics include diaphragm thickness (DT), thickening fraction during inspiration, real-time diaphragmatic excursion, lung diameter changes and changes in pulmonary length and area. These measures have been compared with conventional PFTs in various studies to validate their use for diagnostic accuracy, particularly in early stages of disease.

KEY CONTENT AND FINDINGS: DUS is a non-invasive, widely available tool that strongly correlates with PFT measurements, especially FVC, MIP, and sniff nasal inspiratory pressure (SNIP). Dynamic measures, such as excursion and velocity, appear more sensitive to early dysfunction than thickness alone. Chest dynamic MRI has also shown significant correlations with spirometric parameters. Small cohort studies indicate that dynamic chest MRI is a superior, sensitive tool for detecting early respiratory impairment in asymptomatic patients with normal spirometry.

CONCLUSIONS: Radiological assessments, primarily DUS, DL-based chest CT and dynamic MRI, offer valuable, objective, and non-invasive methods for monitoring respiratory muscle strength in ALS. These techniques serve as complementary tools to traditional PFTs, particularly in selected clinical scenarios such ALS patients with early disease, bulbar involvement and unable to perform PFTs. Further longitudinal research with larger cohorts is needed to standardize protocols and validate their role as early parameters to guide the timely initiation of supportive interventions like non-invasive ventilation (NIV).},
}

@article {pmid42448407,
year = {2026},
author = {Rangappa, N and Upadhyay, R and Lakshman, N and Ramasamy, S and Sevanan, M and Justin, A and Chinnathambi, S},
title = {Small molecular therapeutic targets for neurodegenerative diseases.},
journal = {Advances in protein chemistry and structural biology},
volume = {153},
number = {},
pages = {135-167},
doi = {10.1016/bs.apcsb.2025.10.012},
pmid = {42448407},
issn = {1876-1631},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology/genetics ; Animals ; *Molecular Targeted Therapy ; },
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis disease are characterized by progressive neuronal loss, protein aggregation, and synaptic dysfunction. These diseases share common pathological mechanisms including oxidative stress, mitochondrial impairment, chronic neuroinflammation, protein misfolding, and epigenetic dysregulation. Current therapies offer only symptomatic relief and fail to halt disease progression. Recent advances in transcriptomics and proteomics have enabled the identification of shared molecular pathways and druggable targets across multiple neurodegenerative diseases. The key targets, such as BDNF-TrkB, TREM2, SIRT1, PINK1-Parkin, GSK-3β, NLRP3, and mTOR have shown promise in preclinical models, offering opportunities for broad-spectrum therapeutic development. Importantly, blood-brain barrier disruption and neuroinflammatory crosstalk exacerbate disease pathology and hinder drug delivery. Innovative strategies involving nanocarriers, gene therapy, and epigenetic modulation are emerging to overcome these barriers. This review highlights the convergence of disease mechanisms, discusses common molecular signatures and therapeutic vulnerabilities, and explores novel small molecular interventions targeting shared pathways mainly in AD and PD. A deeper understanding of aging-associated molecular dysfunction is essential to design sustainable, disease-modifying therapeutics with cross-disease relevance.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism/pathology/genetics
Animals
*Molecular Targeted Therapy

@article {pmid42450002,
year = {2026},
author = {Kim, Y and Jung, YK},
title = {Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.},
journal = {International journal of molecular sciences},
volume = {27},
number = {13},
pages = {},
doi = {10.3390/ijms27135730},
pmid = {42450002},
issn = {1422-0067},
support = {RS-2025-00519823//National Research Foundation of Korea/ ; RS-2024-00439842//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Proteasome Endopeptidase Complex/metabolism ; *Neurodegenerative Diseases/metabolism/therapy/pathology/drug therapy ; Animals ; Proteostasis ; *Protein Aggregation, Pathological/metabolism ; *Protein Aggregates ; Proteotoxic Stress ; Ubiquitin/metabolism ; Proteolysis ; Oxidative Stress ; },
abstract = {Neurodegenerative diseases are characterized by the accumulation of misfolded and aggregation-prone proteins, reflecting a failure of proteostasis. The ubiquitin-proteasome system (UPS), a major pathway for selective intracellular protein degradation, is essential for maintaining neuronal protein homeostasis. Proteasome dysfunction has been implicated in several major neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), although its extent and mechanisms vary across disease contexts. In this review, we examine current evidence for proteasome dysfunction in neurodegeneration and discuss how disease-associated proteins impair proteasome function through direct inhibition, defective substrate processing, and sequestration into protein aggregates. We also address the contribution of oxidative stress, neuroinflammation, and aging to proteasome dysregulation. Finally, we highlight emerging therapeutic strategies aimed at restoring proteasome function, including pharmacological activation, modulation of proteasome assembly and stability, and targeted protein degradation approaches. Understanding the context-dependent nature of proteasome dysfunction will be important for developing effective proteostasis-based therapies.},
}

Humans
*Proteasome Endopeptidase Complex/metabolism
*Neurodegenerative Diseases/metabolism/therapy/pathology/drug therapy
Animals
Proteostasis
*Protein Aggregation, Pathological/metabolism
*Protein Aggregates
Proteotoxic Stress
Ubiquitin/metabolism
Proteolysis
Oxidative Stress

@article {pmid42451086,
year = {2026},
author = {Soni, N and Debnath, N and Rekapally, E and Jabbar, A and Tyagi, SC and Bissa, B and Tyagi, N},
title = {Vitamin D Signaling in Neurodegenerative Disorders: Mechanisms, Therapeutic Potential, and Clinical Implications.},
journal = {Nutrients},
volume = {18},
number = {13},
pages = {},
doi = {10.3390/nu18132082},
pmid = {42451086},
issn = {2072-6643},
support = {971566; 24 TPA1304527 and 25 TPA1481771 to Neetu Tyagi.//American Heart Association/ ; },
mesh = {Humans ; *Vitamin D/metabolism/therapeutic use ; *Neurodegenerative Diseases/metabolism/drug therapy/etiology ; *Signal Transduction ; Vitamin D Deficiency/complications ; Animals ; Oxidative Stress/drug effects ; Receptors, Calcitriol/metabolism ; Blood-Brain Barrier/metabolism ; Neuroprotective Agents ; },
abstract = {Vitamin D has long been recognized for its role in calcium homeostasis and bone metabolism; however, it is now emerging as an important regulator of central nervous system (CNS) function. Recent evidence suggests that vitamin D signaling contributes to the pathogenesis and progression of several neurodegenerative disorders. Vitamin D exerts neuroprotective effects through multiple mechanisms, including regulation of calcium homeostasis, modulation of immune responses, reduction in oxidative stress, stimulation of neurotrophic factors, and maintenance of blood-brain barrier (BBB) integrity. Vitamin D receptors and metabolizing enzymes are widely distributed across several brain regions, highlighting their direct involvement in neuronal function. This review summarizes the biosynthesis, metabolism, and signaling pathways of vitamin D. It explores its role in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), stroke, and traumatic brain injury (TBI). Evidence from experimental and clinical studies indicates that vitamin D deficiency is associated with an increased risk and severity of these conditions, while supplementation may provide therapeutic benefits.},
}

Humans
*Vitamin D/metabolism/therapeutic use
*Neurodegenerative Diseases/metabolism/drug therapy/etiology
*Signal Transduction
Vitamin D Deficiency/complications
Animals
Oxidative Stress/drug effects
Receptors, Calcitriol/metabolism
Blood-Brain Barrier/metabolism
Neuroprotective Agents

@article {pmid42451691,
year = {2026},
author = {Singh, AA and Arukha, AP and Song, M},
title = {Indole-Derived Compounds as Redox-Modulators: Antioxidant Mechanisms in Neuronal Protection.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {13},
pages = {},
doi = {10.3390/molecules31132323},
pmid = {42451691},
issn = {1420-3049},
mesh = {Humans ; *Antioxidants/pharmacology/chemistry ; *Indoles/chemistry/pharmacology ; Animals ; *Neuroprotective Agents/pharmacology/chemistry ; Oxidation-Reduction/drug effects ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neurons/drug effects/metabolism ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; Reactive Oxygen Species/metabolism ; },
abstract = {Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis, are distinguished by progressive neuronal dysfunction caused primarily by oxidative stress, mitochondrial impairment, neuroinflammation, and redox imbalance. Growing evidence suggests that indole-derived compounds have significant neuroprotective potential due to their antioxidant, anti-inflammatory, and redox-modulating properties. This review summarizes the structural and biological significance of indole scaffolds, focusing on the mechanisms by which natural, endogenous, microbiota-derived, and synthetic indole compounds protect neuronal networks. Indole-3-carbinol, 3,3'-diindolylmethane, indole-3-propionic acid, and melatonin are major indole derivatives that control important neuroprotective pathways like Nrf2/ARE signaling, mitochondrial bioenergetics, neurotrophic factor expression, apoptotic regulation, and suppression of proinflammatory mediators. These compounds also maintain synaptic plasticity, reduce reactive oxygen species production, and improve neuronal survival in neurodegenerative disease models. Additionally, updated information from translational and clinical research indicates that indole-based compounds may have promising therapeutic applications; however, obstacles like low bioavailability, metabolic instability, and blood-brain barrier penetration continue to be major obstacles to clinical application. Development in nanoparticle delivery systems, microbiome-targeted interventions, and rational structural optimization may improve therapeutic efficacy and translational potential. Overall, indole-derived compounds are a versatile class of redox modulators with potential applications in the prevention and treatment of neurodegenerative diseases via integrated antioxidant and neuroprotective mechanisms.},
}

Humans
*Antioxidants/pharmacology/chemistry
*Indoles/chemistry/pharmacology
Animals
*Neuroprotective Agents/pharmacology/chemistry
Oxidation-Reduction/drug effects
*Neurodegenerative Diseases/drug therapy/metabolism
*Neurons/drug effects/metabolism
Oxidative Stress/drug effects
Signal Transduction/drug effects
Reactive Oxygen Species/metabolism

@article {pmid42455190,
year = {2026},
author = {Lei, Y and Huang, J and Li, M and Zhang, Y and Ye, Z and He, X and Tang, Z and Wei, J},
title = {Effects of respiratory muscle training on respiratory function in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42455190},
issn = {1432-1459},
support = {No. EWT201947//Department of Science and Technology of Hubei Province/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/complications/therapy ; *Breathing Exercises/methods ; *Respiratory Muscles/physiopathology ; },
abstract = {BACKGROUND: Respiratory decline is prognostically important in amyotrophic lateral sclerosis (ALS), but the efficacy of respiratory muscle training (RMT) remains uncertain. We synthesized randomized evidence on respiratory and related outcomes.

METHODS: We searched databases, specialized registers, and trial registries through June 19, 2025, for randomized RMT trials in ALS. Risk of bias was assessed with the Cochrane tool. Random-effects meta-analyses reported standardized mean differences (SMDs) with 95% confidence intervals (CIs), and certainty was rated with GRADE.

RESULTS: Six studies were included; five concurrently randomized trials contributed quantitative data, whereas Pinto 2013 was retained for qualitative context. RMT improved maximal expiratory pressure (MEP; SMD 0.387, 95% CI 0.192-0.581; P = 0.008) and showed small favorable effects on maximal inspiratory pressure (MIP; SMD 0.156, 95% CI 0.089-0.224; P = 0.005), sniff nasal inspiratory pressure (SNIP; SMD 0.216, 95% CI 0.039-0.392; P = 0.034), peak expiratory flow (PEF; SMD 0.205, 95% CI 0.088-0.323; P = 0.017), and ALSFRS-R (SMD 0.214, 95% CI 0.039-0.388; P = 0.030). Forced vital capacity showed a borderline favorable trend (SMD 0.129, 95% CI - 0.003 to 0.262; P = 0.053). Low heterogeneity estimates were imprecise because most endpoints included only three to four small studies. Certainty was moderate for MIP, low for MEP, FVC, and PEF, and very low for SNIP and ALSFRS-R. Exploratory analyses identified no reliable effect modifiers.

CONCLUSIONS: RMT was associated with small, directionally consistent improvements mainly in pressure- and flow-based outcomes, whereas effects on FVC and longer-term clinical outcomes remain uncertain. RMT may be considered an individualized adjunct to ALS respiratory care, not a disease-modifying therapy. Larger, longer, standardized trials with patient-important endpoints are needed.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation/complications/therapy
*Breathing Exercises/methods
*Respiratory Muscles/physiopathology

@article {pmid42455475,
year = {2026},
author = {Maity, D and Gowtham, A and Mishra, Y and Kaundal, RK},
title = {Exosome Biology at the Interface of Neurodegeneration and Therapeutic Innovation.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42455475},
issn = {1559-1182},
mesh = {Humans ; *Exosomes/metabolism ; Animals ; *Neurodegenerative Diseases/therapy/metabolism/pathology ; Biomarkers/metabolism ; },
abstract = {Neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are defined by progressive neuronal loss, protein misfolding, and chronic neuroinflammation, yet effective disease-modifying therapies remain absent. Exosomes have emerged as key mediators of central nervous system communication and are increasingly central to the biology of neurodegeneration. These nanoscale vesicles transport proteins, lipids, and nucleic acids across cellular and anatomical barriers, influencing synaptic function, immune signaling, and metabolic homeostasis. Under pathological conditions, exosomes facilitate the spread of misfolded proteins such as amyloid-β, p-tau, α-synuclein, and TDP-43, thereby accelerating network-level degeneration. At the same time, their cargo exhibits disease-specific molecular signatures detectable in peripheral biofluids, supporting their development as minimally invasive biomarkers for early diagnosis and longitudinal monitoring. Advances in exosome engineering further underscore their potential as therapeutic delivery vehicles capable of crossing the blood-brain barrier and targeting pathogenic pathways with RNA-based therapeutics, proteins, or gene-editing systems. Together, these findings position exosomes as pivotal contributors to both the mechanistic progression and translational targeting of neurodegenerative diseases.},
}

Humans
*Exosomes/metabolism
Animals
*Neurodegenerative Diseases/therapy/metabolism/pathology
Biomarkers/metabolism

@article {pmid41905471,
year = {2026},
author = {Kuiper, MM and Cuppers, L and Sewell-Green, A and Kruithof, WJ and Visser-Meily, JMA and Beelen, A},
title = {Criterion validity of equations as alternatives to reference standards for assessing body composition and energy expenditure in amyotrophic lateral sclerosis - A systematic literature review.},
journal = {Clinical nutrition ESPEN},
volume = {73},
number = {},
pages = {103262},
doi = {10.1016/j.clnesp.2026.103262},
pmid = {41905471},
issn = {2405-4577},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Body Composition ; *Energy Metabolism ; Nutritional Status ; Reference Standards ; Reproducibility of Results ; Electric Impedance ; Nutrition Assessment ; Malnutrition/diagnosis/etiology ; Anthropometry/methods ; },
abstract = {BACKGROUND & AIM: People living with amyotrophic lateral sclerosis (ALS) are at high risk of malnutrition, making it essential to monitor their nutritional status through measurements of body composition and energy expenditure. However, validity of equations, as alternatives to reference standards for assessing these parameters in ALS, is unclear. This systematic review evaluates criterion validity of equations to estimate body composition and energy expenditure in ALS.

METHODS: Four electronic databases (EMBASE, MEDLINE, CINAHL and Cochrane) were systematically searched from inception until July 7th, 2025. Studies were included if criterion validity of an instrument or method for estimating body composition or energy expenditure was examined in people diagnosed with ALS. Methodological quality was assessed using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) risk of bias checklist. Criterion validity was rated as sufficient (+), indeterminate (?) or insufficient (-) based on COSMIN criteria for good measurement properties. Results were qualitatively summarised.

RESULTS: Twelve studies were included: five evaluated the criterion validity of equations to estimate body composition using Bioelectrical Impedance Analysis (BIA) or anthropometry, and seven to estimate resting or total daily energy expenditure. No equation was rated as sufficient for criterion validity across studies.

CONCLUSION: Equations to estimate body composition and energy expenditure should be applied with caution, as no equation exhibited high criterion validity in ALS. ALS-specific equations require further validation, and ideally, new equations tailored to the unique physiological characteristics of ALS should be developed.

PROSPERO REGISTRATION NUMBER: CRD42024573509.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology
*Body Composition
*Energy Metabolism
Nutritional Status
Reference Standards
Reproducibility of Results
Electric Impedance
Nutrition Assessment
Malnutrition/diagnosis/etiology
Anthropometry/methods

@article {pmid40398193,
year = {2025},
author = {Carra, S and Fabian, B and Taghavi, H and Milanetti, E and Giliberti, V and Ruocco, G and Shepherd, J and Vendruscolo, M and Fuxreiter, M},
title = {Virus-like particles of retroviral origin in protein aggregation and neurodegenerative diseases.},
journal = {Molecular aspects of medicine},
volume = {103},
number = {},
pages = {101369},
doi = {10.1016/j.mam.2025.101369},
pmid = {40398193},
issn = {1872-9452},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/virology/pathology ; *Protein Aggregates ; *Endogenous Retroviruses/metabolism/genetics ; *Protein Aggregation, Pathological/metabolism/virology ; Animals ; *Virion/metabolism ; Protein Folding ; },
abstract = {A wide range of human diseases are associated with protein misfolding and amyloid aggregates. Recent studies suggest that in certain neurological disorders, including Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD) and various tauopathies, protein aggregation may be promoted by virus-like particles (VLPs) formed by endogenous retroviruses (ERVs). The molecular mechanisms by which these VLPs contribute to protein aggregation, however, remain enigmatic. Here, we discuss possible molecular mechanisms of ERV-derived VLPs in the formation and spread of protein aggregates. An intriguing possibility is that liquid-like condensates may facilitate the formation of both protein aggregates and ERV-derived VLPs. We also describe how RNA chaperoning, and the encapsulation and trafficking of misfolded proteins, may contribute to protein homeostasis through the elimination of protein aggregates from cells. Based on these insights, we discuss future potential therapeutic opportunities.},
}

Humans
*Neurodegenerative Diseases/metabolism/virology/pathology
*Protein Aggregates
*Endogenous Retroviruses/metabolism/genetics
*Protein Aggregation, Pathological/metabolism/virology
Animals
*Virion/metabolism
Protein Folding

@article {pmid40398684,
year = {2025},
author = {Naufal, E and Shadbolt, C and Wouthuyzen-Bakker, M and Rele, S and Sahebjada, S and Thuraisingam, S and Babazadeh, S and Choong, PF and Dowsey, MM},
title = {Clinical prediction models to guide treatment of periprosthetic joint infections: a systematic review and meta-analysis.},
journal = {The Journal of hospital infection},
volume = {162},
number = {},
pages = {53-61},
doi = {10.1016/j.jhin.2025.04.035},
pmid = {40398684},
issn = {1532-2939},
mesh = {Humans ; *Prosthesis-Related Infections/therapy ; },
abstract = {BACKGROUND: Several clinical prediction models that aim to guide decisions about the management of periprosthetic joint infections (PJIs) have been developed. While some models have been recommended for use in clinical settings, their suitability remains uncertain.

METHODS: We systematically reviewed and critically appraised all multi-variable prediction models for the treatment of PJI. We searched MEDLINE, EMBASE, Web of Science, and Google Scholar from inception until 1[st] March 2024 and included studies that developed or validated models that predict the outcome of PJI. We used PROBAST (Prediction model Risk Of Bias ASsessment Tool) to assess the risk of bias and applicability. Model performance estimates were pooled via random effect meta-analysis.

RESULTS: Thirteen predictive models and seven external validations were identified. Methodological issues were identified in all studies. Pooled estimates indicated that the KLIC (Kidney, Liver, Index surgery, Cemented prosthesis, C-reactive protein) score had fair discriminative performance (pooled c-statistic 0.62, 95% CI 0.55-0.69). Both the τ[2] (0.02) and I[2] (33.4) estimates indicated that between-study heterogeneity was minimal. Meta-analysis indicated Shohat et al.'s model had good discriminative performance (pooled c-statistic 0.74, 95% CI 0.57-0.85). Both the τ[2] (0.0) and I[2] (0.0) indicated that between study heterogeneity was minimal.

CONCLUSIONS: Clinicians should be aware of limitations in the methods used to develop available models to predict outcomes of PJI. As no models have consistently demonstrated adequate performance across external validation studies, it remains unclear whether any available models would provide reliable information if used to guide clinical decision making.},
}

Humans
*Prosthesis-Related Infections/therapy

@article {pmid40400898,
year = {2025},
author = {Aziz, S and Anbreen, S and Shahzad, S and Ahmed, MS and Sharma, V and Yang, J and Ali, L},
title = {Investigating nanoparticle's utilization in stem cell therapy for neurological disorders.},
journal = {American journal of stem cells},
volume = {14},
number = {1},
pages = {1-13},
pmid = {40400898},
issn = {2160-4150},
abstract = {Stem cell therapy is a promising area of regenerative medicine, offering potential treatments for various life-threatening disorders. Stem cells are classified based on their differentiation potential into totipotent, pluripotent, and multipotent stem cells. Among them, mesenchymal stem cells (MSCs) are widely used in regenerative medicine due to their tissue regeneration capabilities and ability to differentiate into multiple cell types. Stem cells are being explored for treating neurodegenerative disorders like Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis (ALS). These conditions result from progressive neuronal degeneration, leading to irreversible damage. Challenges such as cell survival, immune rejection, tumor formation, and ethical concerns related to embryonic stem cells need to be addressed. Nanotechnology is emerging as a tool for enhancing stem cell therapy, improving targeted delivery and effectiveness. Nanoparticles possess the ability to create microenvironments as substrates, facilitate targeted administration, and enable real-time, precise imaging of stem cells. This review explores the integration of stem cells and nanotechnology as regenerative medicine tool for neurodegenerative disease treatment, analyzing current strategies and therapeutic approaches. Integrating nanotechnology with stem cell therapy may significantly improve targeted delivery and enhance regenerative outcomes for neurodegenerative disorders.},
}

@article {pmid40403503,
year = {2025},
author = {Dhapola, R and Paidlewar, M and Kumari, S and Sharma, P and Vellingiri, B and Medhi, B and HariKrishnaReddy, D},
title = {cGAS-STING and neurodegenerative diseases: A molecular crosstalk and therapeutic perspective.},
journal = {International immunopharmacology},
volume = {159},
number = {},
pages = {114902},
doi = {10.1016/j.intimp.2025.114902},
pmid = {40403503},
issn = {1878-1705},
mesh = {Humans ; *Nucleotidyltransferases/metabolism ; *Neurodegenerative Diseases/drug therapy/metabolism/immunology ; *Membrane Proteins/metabolism ; Animals ; Signal Transduction ; STING Protein ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; },
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS) and Frontotemporal Dementia (FTD) share key pathological features, including neuroinflammation, oxidative stress, mitochondrial dysfunction, autophagic dysfunction, and DNA damage. By identifying cytosolic DNA and triggering the type I interferon response, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway regulates neuroinflammation. Dysregulated cGAS-STING signaling has been linked to neuroinflammation and neuronal degeneration across multiple neurodegenerative conditions. In many neurodegenerative disorders, neuroinflammation is mediated by the cGAS-STING pathway. Mitochondrial malfunction and impaired autophagy cause cytosolic DNA buildup in Huntington's, Parkinson's, and Alzheimer's diseases, which activates cGAS-STING and drives chronic inflammation. This pathway is triggered by TDP-43 pathology and nucleic acid dysregulation in ALS and FTD, which leads to neuronal destruction. Both central demyelination and peripheral immunological responses are linked to cGAS-STING activation in multiple sclerosis. Various inhibitors, such as RU.521, H-151, and naturally occurring compounds like metformin, potentially attenuate cGAS-STING-mediated neuroinflammation and associated pathologies. H-151 significantly decreased the expression of pro-inflammatory markers in murine macrophage J774 cells activated with cGAMP: TNF-α by 68 %, IFN-β by 84 %, and CXCL10 by 96 %. cGAS-STING inhibitors target neuroinflammation, offering a disease-modifying approach unlike current symptomatic treatments. However, challenges like blood-brain barrier penetration, off-target effects, and immune suppression hinder clinical translation, necessitating optimized drug delivery and immune modulation. With a focus on its potential for future clinical applications, this review explores the role of the cGAS-STING pathway in neurodegeneration and new treatment approaches.},
}

Humans
*Nucleotidyltransferases/metabolism
*Neurodegenerative Diseases/drug therapy/metabolism/immunology
*Membrane Proteins/metabolism
Animals
Signal Transduction
STING Protein
Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase

@article {pmid40403957,
year = {2025},
author = {Zeng, L and Yang, J and Zhang, C and Zhu, J and Zhong, S and Liu, X and Xie, H and Wang, L and Chen, L and Zhong, M and Hua, F and Liang, W},
title = {Miro1: A potential target for treating neurological disorders.},
journal = {Neuroscience},
volume = {577},
number = {},
pages = {228-239},
doi = {10.1016/j.neuroscience.2025.05.019},
pmid = {40403957},
issn = {1873-7544},
mesh = {Humans ; Animals ; *rho GTP-Binding Proteins/metabolism ; *Nervous System Diseases/metabolism/drug therapy ; *Mitochondria/metabolism ; *Mitochondrial Proteins/metabolism ; Neurons/metabolism ; },
abstract = {The Miro1 protein is a member of the mitochondrial Rho GTPase (Miro) protein family and plays a crucial role in regulating the dynamic processes of mitochondria and participating in cellular movement and mitochondrial transport. In the nervous system, it ensures adequate energy supply for normal neuronal function and synaptic transmission. Additionally, Miro1 actively participates in the regulation of mitochondrial quality control and stress responses within neurons. Its primary function is to sense intracellular stress signals to regulate mitochondrial movement and metabolism, thereby adapting to environmental changes. Multiple studies have indicated that the Miro1 protein is associated with the pathogenesis of various neurological disorders, such as Alzheimer's Disease(AD), Parkinson's Disease(PD), and Amyotrophic Lateral Sclerosis(ALS). This article reviews the mechanistic role of Miro1 in these diseases and summarizes the latest research on its involvement in neurological disorders. These efforts aim to provide unified treatment strategies for certain neurological disorders and explore the potential for treating complex neurological diseases.},
}

Humans
Animals
*rho GTP-Binding Proteins/metabolism
*Nervous System Diseases/metabolism/drug therapy
*Mitochondria/metabolism
*Mitochondrial Proteins/metabolism
Neurons/metabolism

@article {pmid40405223,
year = {2025},
author = {Yoonesi, S and Abedi Azar, R and Arab Bafrani, M and Yaghmayee, S and Shahavand, H and Mirmazloumi, M and Moazeni Limoudehi, N and Rahmani, M and Hasany, S and Idjadi, FZ and Aalipour, MA and Gharedaghi, H and Salehi, S and Asadi Anar, M and Soleimani, MS},
title = {Facial expression deep learning algorithms in the detection of neurological disorders: a systematic review and meta-analysis.},
journal = {Biomedical engineering online},
volume = {24},
number = {1},
pages = {64},
pmid = {40405223},
issn = {1475-925X},
mesh = {Humans ; *Deep Learning ; *Facial Expression ; *Nervous System Diseases/diagnosis ; },
abstract = {BACKGROUND: Neurological disorders, ranging from common conditions like Alzheimer's disease that is a progressive neurodegenerative disorder and remains the most common cause of dementia worldwide to rare disorders such as Angelman syndrome, impose a significant global health burden. Altered facial expressions are a common symptom across these disorders, potentially serving as a diagnostic indicator. Deep learning algorithms, especially convolutional neural networks (CNNs), have shown promise in detecting these facial expression changes, aiding in diagnosing and monitoring neurological conditions.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the performance of deep learning algorithms in detecting facial expression changes for diagnosing neurological disorders.

METHODS: Following PRISMA2020 guidelines, we systematically searched PubMed, Scopus, and Web of Science for studies published up to August 2024. Data from 28 studies were extracted, and the quality was assessed using the JBI checklist. A meta-analysis was performed to calculate pooled accuracy estimates. Subgroup analyses were conducted based on neurological disorders, and heterogeneity was evaluated using the I[2] statistic.

RESULTS: The meta-analysis included 24 studies from 2019 to 2024, with neurological conditions such as dementia, Bell's palsy, ALS, and Parkinson's disease assessed. The overall pooled accuracy was 89.25% (95% CI 88.75-89.73%). High accuracy was found for dementia (99%) and Bell's palsy (93.7%), while conditions such as ALS and stroke had lower accuracy (73.2%).

CONCLUSIONS: Deep learning models, particularly CNNs, show strong potential in detecting facial expression changes for neurological disorders. However, further work is needed to standardize data sets and improve model robustness for motor-related conditions.},
}

Humans
*Deep Learning
*Facial Expression
*Nervous System Diseases/diagnosis

@article {pmid40405710,
year = {2025},
author = {Clift, A and Rowen, D and Knox, L and Griffiths, AW and McDermott, CJ},
title = {A Systematic Review of Attributes Influencing Preferences for Treatments and Interventions in People With Amyotrophic Lateral Sclerosis (ALS).},
journal = {Muscle & nerve},
volume = {72},
number = {3},
pages = {359-382},
pmid = {40405710},
issn = {1097-4598},
support = {//National Institute for Health and Care Research/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/psychology ; *Patient Preference/psychology ; Quality of Life/psychology ; Patient-Centered Care ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that has no cure, and treatments predominantly focus on improving quality of life. Patient-centred care is central to bringing about meaningful improvements to quality of life. This review addresses the lack of consolidated evidence on what matters most to people with ALS (pwALS) by synthesizing 44 preference-based studies covering six different treatment and intervention categories. Data-based convergent synthesis identified five overarching factors influencing preferences: ease of use, accessibility, making life easier, autonomy, and safety/reliability. Simplifying and enhancing accessibility of treatment delivery across disease stages aligns with the nature of neurodegenerative disorders such as ALS, where function declines as the disease progresses. The value in perceived and real control reflects the profound impact ALS has on an individual's independence. Safety and reliability are crucial for people with ALS and are recognized as fundamental requirements for quality healthcare. The themes identified in this review can inform the attributes of preference elicitation methods. Systematically varying the levels of these attributes elicits quantitative measures of preferences. These findings can be used to inform and develop healthcare policy and clinical practice in ALS care. Specifically, preferences related to drug treatments can then be integrated into target product profiles (TPPs) to align drug development with the needs and values of pwALS. Integrating patient preferences into clinical practice promotes patient-centred care, increasing both patient satisfaction and treatment effectiveness.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/psychology
*Patient Preference/psychology
Quality of Life/psychology
Patient-Centered Care

@article {pmid40406043,
year = {2025},
author = {Wang, L and Ma, L and Gao, Z and Wang, Y and Qiu, J},
title = {Significance of gene therapy in neurodegenerative diseases.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1515255},
pmid = {40406043},
issn = {1662-4548},
abstract = {Gene therapy is an approach that employs vectors to deliver genetic material to target cells, aiming to correct genes with pathogenic mutations and modulate one or more genes responsible for disease progression. It holds significant value for clinical applications and offers broad market potential due to the large patient population affected by various conditions. For instance, in 2023, the Food and Drug Administration (FDA) approved 55 new drugs, including five specifically for gene therapy targeting hematologic and rare diseases. Recently, with advancements in understanding the pathogenesis and development of neurodegenerative diseases (NDDs), gene therapy has emerged as a promising avenue for treating Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA), particularly in personalized medicine. Notably, the FDA has approved three clinical applications for combating SMA, utilizing viral vectors delivered via intravenous and intrathecal injections. However, gene therapy for other NDDs remains in clinical trials, necessitating improvements in viral vectors, exploration of new vectors, optimization of delivery routes, and further investigation into pathogenesis to identify novel targets. This review discusses recent advancements in gene therapy for NDDs, offering insights into developing new therapeutic strategies.},
}

@article {pmid40411245,
year = {2026},
author = {Giacobbe, A and Hiana, J and Wang, O and Benatar, M and Wicks, P and Mascias Cadavid, J and Jhooty, S and McDermott, C and Pattee, G and Bertorini, T and Heiman-Patterson, T and Ratner, D and Barkhaus, P and Carter, G and Jackson, C and Denson, K and Brown, A and Armon, C and Sun, Y and Nguyen, A and Bedlack, R and Li, X},
title = {ALSUntangled #79: alpha-lipoic acid.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {27},
number = {1-2},
pages = {233-237},
doi = {10.1080/21678421.2025.2507166},
pmid = {40411245},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Thioctic Acid/therapeutic use ; *Antioxidants/therapeutic use ; Animals ; },
abstract = {Alpha-lipoic acid (ALA) is a naturally occurring fatty acid. It serves as an essential cofactor for enzymatic reactions in mitochondrial energy production, is a potent antioxidant and has anti-inflammatory effects, which are plausible mechanisms in slowing ALS progression. In ALS preclinical studies, ALA slowed motor function decline and improved survival. There were self-reported cases of improved muscle strength in ALS patients when ALA was taken with numerous additional supplements, making it difficult to discern its efficacy. One small, 6-month open-label study showed improved quality of life, fatigue, and mood after participants took it with B vitamins and amino acids for the first 3 months. So far, no clinical trials have been published in people living with amyotrophic lateral sclerosis (PALS). Given the insufficient clinical data, we cannot endorse ALA and will support more research on its efficacy in slowing ALS progression.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Thioctic Acid/therapeutic use
*Antioxidants/therapeutic use
Animals

@article {pmid40414644,
year = {2025},
author = {Manusha, S and Varsha, N and Varshini, R and Sivamani, Y and Pokkuluri, KS and Elayaperumal, S},
title = {Altered microbiome influence on the enteric neuromuscular system in amyotrophic lateral sclerosis (ALS).},
journal = {International review of neurobiology},
volume = {180},
number = {},
pages = {95-123},
doi = {10.1016/bs.irn.2025.04.006},
pmid = {40414644},
issn = {2162-5514},
mesh = {*Amyotrophic Lateral Sclerosis/microbiology/physiopathology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Enteric Nervous System/physiopathology/microbiology ; *Dysbiosis/physiopathology ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurological disease marked by the degeneration of motor neurons, leading to muscle weakness and paralysis. While the cause of ALS is uncertain, research indicates that changes in the gut microbiome may influence the disease's progression. This chapter explores how alterations in gut microbiota affect the enteric neuromuscular system (ENS) in ALS. In ALS patients, disrupted gut microbiota are linked to the brain-gut axis, impacting both gastrointestinal function and neuronal health. Studies show that microbial changes are associated with inflammation, immune instability, and neurodegeneration, which exacerbate the disease. Gastrointestinal issues like constipation and dysphagia in ALS are tied to ENS dysregulation. Understanding the connections between the gut microbiome, ENS, and central nervous system (CNS) may lead to novel therapies targeting neurodegeneration and microbial dysbiosis in ALS.},
}

*Amyotrophic Lateral Sclerosis/microbiology/physiopathology
Humans
*Gastrointestinal Microbiome/physiology
*Enteric Nervous System/physiopathology/microbiology
*Dysbiosis/physiopathology
Animals

@article {pmid40419749,
year = {2025},
author = {Monteiro Neto, JR and de Souza, GF and Dos Santos, VM and de Holanda Paranhos, L and Ribeiro, GD and Magalhães, RSS and Queiroz, DD and Eleutherio, ECA},
title = {SOD1, A Crucial Protein for Neural Biochemistry: Dysfunction and Risk of Amyotrophic Lateral Sclerosis.},
journal = {Molecular neurobiology},
volume = {62},
number = {11},
pages = {14966-14986},
pmid = {40419749},
issn = {1559-1182},
support = {201.174/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; PROBRAL 88881.986154/2024-01//CAPES-DAAD/ ; 309635/2023-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/enzymology/metabolism/pathology/genetics ; Humans ; *Superoxide Dismutase-1/metabolism ; Animals ; *Neurons/metabolism/pathology ; Oxidative Stress/physiology ; Risk Factors ; },
abstract = {Neurons are very susceptible to oxidative stress. They are the major consumers of oxygen in the brain, which is used to provide energy through oxidative phosphorylation, the major source of reactive oxygen species (ROS). In addition, compared to other tissues, neurons have lower levels of catalase and glutathione and increased susceptibility to lipid peroxidation due to the elevated levels of unsaturated fatty acids. These characteristics increasingly emphasize the antioxidant enzyme Cu/Zn superoxide dismutase 1 (SOD1) to maintain neuronal redox homeostasis. In the last decade, SOD1 gained additional roles which are also important to the metabolism of neurons. SOD1 controls the production of ROS by the electron transport chain, activates the expression of genes involved in the protection against oxidative stress, and regulates the shift from oxidative to fermentative metabolism involved in astrocyte-neuron metabolic cooperation. Furthermore, impaired interaction between the phosphatase calcineurin and SOD1 seems to result in TDP-43 hyperphosphorylation, the main proteinopathy found in amyotrophic lateral sclerosis (ALS) patients. However, this enzyme is ubiquitously expressed, mutated, and damaged forms of SOD1 cause disease in motor neurons. In this review, we discuss the pivotal functions of SOD1 in neuronal biochemistry and their implications for ALS.},
}

*Amyotrophic Lateral Sclerosis/enzymology/metabolism/pathology/genetics
Humans
*Superoxide Dismutase-1/metabolism
Animals
*Neurons/metabolism/pathology
Oxidative Stress/physiology
Risk Factors

@article {pmid40422183,
year = {2025},
author = {Verde, EM and Secco, V and Ghezzi, A and Mandrioli, J and Carra, S},
title = {Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.},
journal = {Cells},
volume = {14},
number = {10},
pages = {},
pmid = {40422183},
issn = {2073-4409},
support = {SUMOsolvable//AriSLA/ ; AHA MCA 2022//Giovanni Armenise-Harvard Foundation and AirAlzh/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Frontotemporal Dementia/metabolism/pathology/genetics ; *Protein Aggregates ; *Protein Aggregation, Pathological/metabolism ; Animals ; Protein Processing, Post-Translational ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share common genes and pathomechanisms and are referred to as the ALS-FTD spectrum. A hallmark of ALS-FTD pathology is the abnormal aggregation of proteins, including Cu/Zn superoxide dismutase (SOD1), transactive response DNA-binding protein 43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), and dipeptide repeat proteins resulting from C9orf72 hexanucleotide expansions. Genetic mutations linked to ALS-FTD disrupt protein stability, phase separation, and interaction networks, promoting misfolding and insolubility. This review explores the molecular mechanisms underlying protein aggregation in ALS-FTD, with a particular focus on TDP-43, as it represents the main aggregated species inside pathological inclusions and can also aggregate in its wild-type form. Moreover, this review describes the protective mechanisms activated by the cells to prevent protein aggregation, including molecular chaperones and post-translational modifications (PTMs). Understanding these regulatory pathways could offer new insights into targeted interventions aimed at mitigating cell toxicity and restoring cellular function.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
*DNA-Binding Proteins/metabolism/genetics
*Frontotemporal Dementia/metabolism/pathology/genetics
*Protein Aggregates
*Protein Aggregation, Pathological/metabolism
Animals
Protein Processing, Post-Translational

@article {pmid40426973,
year = {2025},
author = {Ivantsik, O and Exarchos, TP and Vrahatis, AG and Vlamos, P and Krokidis, MG},
title = {Exploring Protein Misfolding in Amyotrophic Lateral Sclerosis: Structural and Functional Insights.},
journal = {Biomedicines},
volume = {13},
number = {5},
pages = {},
pmid = {40426973},
issn = {2227-9059},
support = {TAEDR-0535850.//This work was partially supported by the European Union-Next Generation EU, Greece 2.0 Na-tional Recovery and Resilience Plan Flagship program TAEDR-0535850./ ; },
abstract = {Protein functionality depends on its proper folding, making protein misfolding crucial for the function of proteins and, by extension, cells and the whole organism. Increasing evidence supports the role of protein misfolding in the pathogenesis of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). ALS is a rapidly progressive disease diagnosed at a prevalence of 5 cases per 100,000, with approximately 2-3 patients per 100,000 diagnosed each year. To date, there is no cure, and the disease usually leads to death within 2 to 5 years from diagnosis. There are two types of the disorder: familial ALS (fALS), accounting for approximately 10% of cases, and sporadic (sALS), accounting for the remaining 90%. The hallmark of ALS, regardless of type, is the protein aggregates found in patients' tissues. This suggests that the disruption of proteostasis plays a critical role in the development of the disease. Herein, we stress the distinct factors that lead to protein misfolding and aggregate formation in ALS. Specifically, we highlight several triggering factors affecting protein misfolding, namely mutations, errors in the processes of protein production and trafficking, and failures of folding and chaperone machinery. Gaining a deeper understanding of protein aggregation will improve our comprehension of disease pathogenesis and potentially uncover new therapeutic approaches.},
}

@article {pmid40427436,
year = {2025},
author = {Minuti, A and Raffaele, I and Scuruchi, M and Lui, M and Muscarà, C and Calabrò, M},
title = {Role and Functions of Irisin: A Perspective on Recent Developments and Neurodegenerative Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {5},
pages = {},
pmid = {40427436},
issn = {2076-3921},
support = {Current Research Funds 2025 (RRC-2025-23686388)//Ministero della Salute/ ; },
abstract = {Irisin is a peptide derived from fibronectin type III domain-containing protein 5 (FNDC5) and is primarily produced by muscle fibers under the regulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) during exercise. Irisin has been the subject of extensive research due to its potential as a metabolic regulator and its antioxidant properties. Notably, it has been associated with protective actions within the brain. Despite growing interest, many questions remain regarding the molecular mechanisms underlying its effects. This review summarizes recent findings on irisin, highlighting its pleiotropic functions and the biological processes and molecular cascades involved in its action, with a particular focus on the central nervous system. Irisin plays a crucial role in neuron survival, differentiation, growth, and development, while also promoting mitochondrial homeostasis, regulating apoptosis, and facilitating autophagy-processes essential for normal neuronal function. Emerging evidence suggests that irisin may improve conditions associated with non-communicable neurological diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and multiple sclerosis. Given its diverse benefits, irisin holds promise as a novel therapeutic agent for preventing and treating neurological diseases.},
}

@article {pmid40427919,
year = {2025},
author = {Howarth, NE and Ji, C and Batten, J and Pearce, AJ and Dawes, H and White, AJ and DeLuca, G and Bureau, S and Nowinski, CJ and Miller, MA},
title = {Neurodegenerative Disease and Association Football (NDAF): Systematic Review and Meta-Analysis.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {5},
pages = {},
pmid = {40427919},
issn = {1660-4601},
mesh = {Humans ; *Neurodegenerative Diseases/epidemiology/etiology ; *Soccer/injuries ; *Football/injuries ; Risk Factors ; },
abstract = {There is increasing concern that head injuries in Association Football (or soccer) may lead to adverse health outcomes. The aim of this study was to determine whether head impacts or injuries are associated with an increased risk of neurodegenerative disease. We performed a systematic search using PubMed, Embase, and Ovid (up to April 2025). Studies included investigated neurodegenerative diseases in football in comparison to control athletic and general populations. Data were extracted according to PRISMA guidelines. Studies with an odds ratio (OR) were included in the meta-analysis. A total of ten studies were included in this review, of which nine were suitable for meta-analysis from eight cohorts. The risk for developing any neurodegeneration was 1.69 OR (95%CI 1.11 to 2.59; p = 0.01); for Dementia, it was 2.16 OR (95%CI 1.60 to 2.93; p < 0.01; for Motor Neurone Disease (MND), it was 1.39 OR (95%CI 0.67 to 2.53; p = 0.21); for Parkinson's Disease (PD), it was 1.14 OR (95%CI 0.55 to 2.89; p = 0.79). Heterogeneity was reduced following the removal of two studies and the revised risk scores for any neurodegenerative disease; Dementia increased, with that for MND reaching significance, 1.81 OR (95%CI 1.22 to 2.30; p = 0.01), but there remained no association with PD. Evidence suggests that professional football significantly increases the odds of neurodegenerative disease.},
}

Humans
*Neurodegenerative Diseases/epidemiology/etiology
*Soccer/injuries
*Football/injuries
Risk Factors

@article {pmid40428092,
year = {2025},
author = {Vaccarino, F and Quattrocchi, CC and Parillo, M},
title = {Susceptibility-Weighted Imaging (SWI): Technical Aspects and Applications in Brain MRI for Neurodegenerative Disorders.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {5},
pages = {},
pmid = {40428092},
issn = {2306-5354},
abstract = {Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) sequence sensitive to substances that alter the local magnetic field, such as calcium and iron, allowing phase information to distinguish between them. SWI is a 3D gradient-echo sequence with high spatial resolution that leverages both phase and magnitude effects. The interaction of paramagnetic (such as hemosiderin and deoxyhemoglobin), diamagnetic (including calcifications and minerals), and ferromagnetic substances with the local magnetic field distorts it, leading to signal changes. Neurodegenerative diseases are typically characterized by the progressive loss of neurons and their supporting cells within the neurovascular unit. This cellular decline is associated with a corresponding deterioration of both cognitive and motor abilities. Many neurodegenerative disorders are associated with increased iron accumulation or microhemorrhages in various brain regions, making SWI a valuable diagnostic tool in clinical practice. Suggestive SWI findings are known in Parkinson's disease, Lewy body dementia, atypical parkinsonian syndromes, multiple sclerosis, cerebral amyloid angiopathy, amyotrophic lateral sclerosis, hereditary ataxias, Huntington's disease, neurodegeneration with brain iron accumulation, and chronic traumatic encephalopathy. This review will assist radiologists in understanding the technical framework of SWI sequences for a correct interpretation of currently established MRI findings and for its potential future clinical applications.},
}

@article {pmid40428407,
year = {2025},
author = {Škarica, M and Acsadi, G and Živković, SA},
title = {Pontocerebellar Hypoplasia Type 1 and Associated Neuronopathies.},
journal = {Genes},
volume = {16},
number = {5},
pages = {},
pmid = {40428407},
issn = {2073-4425},
mesh = {Humans ; *Olivopontocerebellar Atrophies/genetics/pathology ; *Cerebellar Diseases/genetics/pathology ; },
abstract = {Pontocerebellar hypoplasia is a rare neurodegenerative syndrome characterized by severe hypoplasia or atrophy of pons and cerebellum that may be associated with other brain malformations, microcephaly, optic nerve atrophy, dystonia, ataxia and neuromuscular disorders. At this time, there are 17 variants of PCH distinguished by clinical presentation and distinctive radiological and biochemical features in addition to pontine and cerebellar hypoplasia. PCH1 is defined as PCH variant associated with anterior horn degeneration in the spinal cord with muscle weakness and hypotonia, and is associated with recessive variants in genes VRK1, EXOSC3, EXOSC8, EXOSC9 and SLC25A46. Neuromuscular manifestations may clinically present as amyotrophic lateral sclerosis (ALS), motor neuropathy (HMN) or neuronopathy (non-5q spinal muscular atrophy; SMA) or sensorimotor polyneuropathy (HMSN). Physiologic functions of PCH1-associated genes include regulation of RNA metabolism, mitochondrial fission and neuronal migration. Overall, complex phenotypes associated with PCH1 gene variants ranging from PCH and related neurodevelopmental disorders combined with neuromuscular disorders to isolated neuromuscular disorders have variable outcomes with isolated neuromuscular disorders typically having later onset with better outcomes. Improved understanding of pathogenesis of pontocerebellar hypoplasia and its association with motor neuronopathies and peripheral neuropathies may provide us with valuable insights and lead to potential new therapeutic targets for neurodegenerative disorders.},
}

Humans
*Olivopontocerebellar Atrophies/genetics/pathology
*Cerebellar Diseases/genetics/pathology

@article {pmid40429767,
year = {2025},
author = {Bokulic Panichi, L and Stanca, S and Dolciotti, C and Bongioanni, P},
title = {The Role of Oligodendrocytes in Neurodegenerative Diseases: Unwrapping the Layers.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40429767},
issn = {1422-0067},
mesh = {Humans ; *Oligodendroglia/metabolism/pathology ; *Neurodegenerative Diseases/pathology/metabolism/etiology ; Animals ; Myelin Sheath/metabolism/pathology ; },
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis/motor neuron disease, and multiple sclerosis, are characterized by progressive loss of neuronal structure and function, leading to severe cognitive, motor, and behavioral impairments. They pose a significant and growing challenge due to their rising prevalence and impact on global health systems. The societal and emotional toll on patients, caregivers, and healthcare infrastructures is considerable. While significant progress has been made in elucidating the pathological hallmarks of these disorders, the underlying cellular and molecular mechanisms remain incompletely understood. Increasing evidence implicates oligodendrocytes and their progenitors-oligodendrocyte progenitor cells (OPCs)-in the pathogenesis of several NDs, beyond their traditionally recognized role in demyelinating conditions such as MS. Oligodendrocytes are essential for axonal myelination, metabolic support, and neural circuit modulation in the central nervous system. Disruptions in oligodendrocyte function and myelin integrity-manifesting as demyelination, hypomyelination, or dysmyelination-have been associated with disease progression in various neurodegenerative contexts. This review consolidates recent findings on the role of OPCs in NDs, explores the concept of myelin plasticity, and discusses therapeutic strategies targeting oligodendrocyte dysfunction. By highlighting emerging research in oligodendrocyte biology, this review aims to provide a short overview of its relevance to neurodegenerative disease progression and potential therapeutic advances.},
}

Humans
*Oligodendroglia/metabolism/pathology
*Neurodegenerative Diseases/pathology/metabolism/etiology
Animals
Myelin Sheath/metabolism/pathology

@article {pmid40431734,
year = {2025},
author = {Kim, DH and Kim, JH and Jeon, MT and Kim, KS and Kim, DG and Choi, IS},
title = {The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
pmid = {40431734},
issn = {1999-4915},
support = {25-BR-02-03//Korea Brain Research Institute/ ; },
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *COVID-19/complications/metabolism/virology/pathology ; *SARS-CoV-2/physiology ; *Neurodegenerative Diseases/metabolism/virology/pathology/etiology ; Virus Replication ; Animals ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins of SARS-CoV-2 have been shown to induce pathological changes in TDP-43 through its cleavage, aggregation, and mislocalization. SARS-CoV-2 infection can cause liquid-liquid phase separation and stress granule formation, which accelerate the condensation of TDP-43, resulting in host RNA metabolism disruption. TDP-43 has been proposed to interact with SARS-CoV-2 RNA, though its role in viral replication remains to be fully elucidated. This interaction potentially facilitates viral replication, while viral-induced oxidative stress and protease activity accelerate TDP-43 pathology. Evidence from both clinical and experimental studies indicates that SARS-CoV-2 infection may contribute to long-term neurological sequelae, including amyotrophic lateral sclerosis-like and frontotemporal dementia-like features, as well as increased phosphorylated TDP-43 deposition in the central nervous system. Biomarker studies further support the link between TDP-43 dysregulation and neurological complications of long-term effects of COVID-19 (long COVID). In this review, we presented a novel integrative framework of TDP-43 pathology, bridging a gap between SARS-CoV-2 infection and mechanisms of neurodegeneration. These findings underscore the need for further research to clarify the TDP-43-related neurodegeneration underlying SARS-CoV-2 infection and to develop therapeutic strategies aimed at mitigating long-term neurological effects in patients with long COVID.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics
*COVID-19/complications/metabolism/virology/pathology
*SARS-CoV-2/physiology
*Neurodegenerative Diseases/metabolism/virology/pathology/etiology
Virus Replication
Animals

@article {pmid40439808,
year = {2025},
author = {Singh, H and Gupta, R and Gupta, M and Ahmad, A},
title = {Aging-induced alterations in microglial cells and their impact on neurodegenerative disorders.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {515},
pmid = {40439808},
issn = {1573-4978},
mesh = {Humans ; *Microglia/metabolism/pathology ; *Neurodegenerative Diseases/metabolism/pathology ; *Aging/pathology/metabolism ; Animals ; Brain/metabolism/pathology ; Cellular Senescence ; },
abstract = {Senescence causes deterioration in the functioning and physiology of an organism. Microglia, the standing resident immune brain cells transform from neuroprotective to neurotoxic with age. Rapid process motility and cellular migration of microglia in the developing brain, and other characteristics are regarded to be crucial for immunological defense and tissue repair. As they mature, microglia not only differ in their morphology but also in their functioning. However, the exact mechanism related to the atrophies caused by aged microglia or their role in neurodegenerative diseases is still uncertain. The aim of this updated review is to provide insights of how aging microglial cells change and how this influences the development of neurodegenerative diseases. As life expectancy rises, there is an increase in the accumulation of iron, ROS/NOS, protein misfolding and insufficient clearing of debris. This is attributed to the age-dependent alterations in the genes linked to energy metabolism, mitochondrial and lysosome function, and neuroinflammation. Aging microglia often shifts towards a pro-inflammatory state with a reduction of anti-inflammatory cytokines. Aging microglia fail to clear amyloid-beta plaques, accelerates tau-pathology and enhances the chronic neuroinflammation, exacerbating the α-synuclein aggregation. These changes significantly impacted the onset of various neurogenerative disorders such as amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease etc. However, it is important to note that these microglial aging effects might not be perceived as absolute, due to various limitations such as microglial heterogeneity, intercellular complexity across brain regions and variability in human aging owing to genetic and epigenetic variations. Regardless of this the future perspective of such insights are of immense relevance as novel therapeutic approaches can be formulated if the molecular and cellular mechanisms of aging microglial perturbations are understood. Future research should focus on restoring microglial homeostasis to mitigate the effects of aging on the brain and slowing the progression of neurodegenerative diseases.},
}

Humans
*Microglia/metabolism/pathology
*Neurodegenerative Diseases/metabolism/pathology
*Aging/pathology/metabolism
Animals
Brain/metabolism/pathology
Cellular Senescence

@article {pmid40439916,
year = {2025},
author = {Porel, P and Hunjan, G and Kaur, N and Sharma, V and Kaur, M and Mittal, Y and Kaur, R and Aran, KR},
title = {Unlocking the neuroprotective potential of peptide nucleic acids 5 (PNA5) in neurological diseases: molecular mechanisms to therapeutic approaches.},
journal = {Metabolic brain disease},
volume = {40},
number = {5},
pages = {213},
pmid = {40439916},
issn = {1573-7365},
mesh = {Humans ; *Peptide Nucleic Acids/therapeutic use/pharmacology ; Animals ; *Nervous System Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; Blood-Brain Barrier/drug effects/metabolism ; },
abstract = {Peptide nucleic acids (PNAs) are synthetic nucleic acid analogues offering distinct structural and functional advantages over conventional RNA and DNA, positioning them as powerful molecules in molecular biology. Recently, PNAs have gained significant attention for their potential in the prevention and management of neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury (TBI), spinal cord injury (SCI), depression, and anxiety. PNA5, a specific PNA variant, is highly expressed in neocortical association regions, particularly in primates, and plays a critical role in high-level cognitive functions such as reasoning, decision-making, and problem-solving. It can form stable, sequence-specific hybridizations with nucleic acids, resist nuclease degradation, and efficiently cross cellular membranes, making them ideal candidates for targeting disease-related genes in the brain. PNA5 has shown neuroprotective properties by improving cognitive function, reducing neuroinflammation, and preserving the integrity of the blood-brain barrier (BBB). Additionally, it supports critical processes such as neural migration, axon guidance, and synaptogenesis, which are vital for maintaining proper brain function. This review explores the mechanisms by which PNAs, particularly PNA5, exert therapeutic effects in neurological disorders. It highlights their role in gene modulation, protein regulation, and potential strategies for enhancing PNA delivery to the central nervous system (CNS) and its related disorders.},
}

Humans
*Peptide Nucleic Acids/therapeutic use/pharmacology
Animals
*Nervous System Diseases/drug therapy/metabolism
*Neuroprotective Agents/therapeutic use/pharmacology
Blood-Brain Barrier/drug effects/metabolism

@article {pmid40446958,
year = {2025},
author = {Yuan, L and Yang, Y and Guo, Y and Deng, H},
title = {Genetic architecture of amyotrophic lateral sclerosis: a comprehensive review.},
journal = {Journal of genetics and genomics = Yi chuan xue bao},
volume = {52},
number = {10},
pages = {1155-1176},
doi = {10.1016/j.jgg.2025.05.008},
pmid = {40446958},
issn = {1673-8527},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology ; Humans ; Animals ; *Genetic Predisposition to Disease ; Disease Models, Animal ; },
abstract = {Amyotrophic lateral sclerosis (ALS), one of the most prevalent neurodegenerative disorders, is pathologically characterized by the progressive degeneration of both upper and lower motor neurons, leading to muscle weakness, paralysis, and death within 2-4 years post-diagnosis. ALS is categorized into familial ALS (FALS) and sporadic ALS, with FALS accounting for approximately 10% of ALS cases. As a genetically heterogeneous disease, ALS exhibits diverse inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked transmission, and genetic factors play pivotal roles in disease pathogenesis. To date, at least 34 disease-causing loci and 32 genes for ALS have been identified. The investigations of mutant protein products and the establishment of animal models have unraveled potential pathogenic pathways, offering insights into the mechanisms of neurodegeneration in ALS. This review focuses on ALS clinical characteristics, neuropathological features, causative loci/genes, genetic susceptibility factors, animal models, and pathogenic mechanisms, with particular attention to recent advances in genetic findings and pathogenic pathways of ALS. Elucidation of the genetic basis of ALS could provide the scientific foundation for personalized treatments to address this recalcitrant disease.},
}

*Amyotrophic Lateral Sclerosis/genetics/pathology
Humans
Animals
*Genetic Predisposition to Disease
Disease Models, Animal

@article {pmid40454774,
year = {2025},
author = {Madrer, N and Perera, ND and Uccelli, NA and Abbondanza, A and Andersen, JV and Carsana, EV and Demmings, MD and Fernandez, RF and de Fragas, MG and Gbadamosi, I and Kulshrestha, D and Lima-Filho, RAS and Marian, OC and Markussen, KH and McGovern, AJ and Neal, ES and Sarkar, S and Šimončičová, E and Soto-Verdugo, J and Yandiev, S and Fernández-Moncada, I},
title = {Neural Metabolic Networks: Key Elements of Healthy Brain Function.},
journal = {Journal of neurochemistry},
volume = {169},
number = {6},
pages = {e70084},
pmid = {40454774},
issn = {1471-4159},
mesh = {Humans ; *Brain/metabolism ; Animals ; *Nerve Net/metabolism ; *Energy Metabolism/physiology ; *Metabolic Networks and Pathways/physiology ; *Neurons/metabolism ; },
abstract = {Neural networks are responsible for processing sensory stimuli and driving the synaptic activity required for brain function and behavior. This computational capacity is expensive and requires a steady supply of energy and building blocks to operate. Importantly, the neural networks are composed of different cell populations, whose metabolic profiles differ between each other, thus endowing them with different metabolic capacities, such as, for example, the ability to synthesize specific metabolic precursors or variable proficiency to manage their metabolic waste. These marked differences likely prompted the emergence of diverse intercellular metabolic interactions, in which the shuttling and cycling of specific metabolites between brain cells allows the separation of workload and efficient control of energy demand and supply within the central nervous system. Nevertheless, our knowledge about brain bioenergetics and the specific metabolic adaptations of neural cells still warrants further studies. In this review, originated from the Fourth International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Schmerlenbach, Germany (2022), we describe and discuss the specific metabolic profiles of brain cells, the intercellular metabolic exchanges between these cells, and how these bioenergetic activities shape synaptic function and behavior. Furthermore, we discuss the potential role of faulty brain metabolic activity in the etiology and progression of Alzheimer's disease, Parkinson disease, and Amyotrophic lateral sclerosis. We foresee that a deeper understanding of neural networks metabolism will provide crucial insights into how higher-order brain functions emerge and reveal the roots of neuropathological conditions whose hallmarks include impaired brain metabolic function.},
}

Humans
*Brain/metabolism
Animals
*Nerve Net/metabolism
*Energy Metabolism/physiology
*Metabolic Networks and Pathways/physiology
*Neurons/metabolism

@article {pmid40459673,
year = {2025},
author = {Dengri, C and Mayberry, W and Koriesh, A and Nouh, A},
title = {Neurology of Androgens and Androgenic Supplements.},
journal = {Current neurology and neuroscience reports},
volume = {25},
number = {1},
pages = {39},
pmid = {40459673},
issn = {1534-6293},
mesh = {Humans ; *Androgens/metabolism/therapeutic use ; *Nervous System Diseases/drug therapy/metabolism ; *Dietary Supplements ; Receptors, Androgen/metabolism ; Animals ; Testosterone/therapeutic use ; },
abstract = {PURPOSE OF REVIEW: This article explores the intricate relationship between androgens, androgen receptors, and the central nervous system. We examine the role of physiologically derived androgens and androgenic supplements in neurodevelopment and neuroplasticity and delve into the involvement of androgen pathways in the pathogenesis of various neurological disorders.

RECENT FINDINGS: This review highlights the increasing recognition of testosterone and androgen signaling in various neurological conditions, with evidence of both protective and harmful effects depending on dosage and context. Although limited to experimental use, testosterone replacement therapy (TRT) may serve potential benefits in the management of multiple sclerosis, epilepsy, headache, Duchenne muscular dystrophy, amyotrophic lateral sclerosis, and Parkinson disease. On the other hand, androgen-blocking treatments may help alter disease progression in spinal and bulbar muscular atrophy. Testosterone supplementation can have potential adverse events when used at a supratherapeutic level, and prenatal testosterone exposure is believed to contribute to the pathogenesis of neurodevelopmental disease. Additionally, androgen-blocking agents could increase the risk of neurodegenerative conditions, such as Parkinson disease and Alzheimer disease. Despite the above findings, there is no established indication of TRT or androgen-blocking medication in neurological disorders. The body of evidence highlighting the involvement of androgens and androgen receptors (ARs) in pathogenesis of neurological diseases is growing. This includes ongoing research exploring the potential therapeutic targets involving the androgen signaling pathway for management of neurological disorders. Future placebo-controlled clinical trials are essential to determine the efficacy and safety of TRT or androgen-blocking therapies in managing neurological disease.},
}

Humans
*Androgens/metabolism/therapeutic use
*Nervous System Diseases/drug therapy/metabolism
*Dietary Supplements
Receptors, Androgen/metabolism
Animals
Testosterone/therapeutic use

@article {pmid40460337,
year = {2025},
author = {van Unnik, JWJ and Ing, L and Oliveira Santos, M and McDermott, CJ and de Carvalho, M and van Eijk, RPA},
title = {Remote Monitoring of Amyotrophic Lateral Sclerosis Using Digital Health Technologies: Shifting Toward Digitalized Care and Research?.},
journal = {Neurology},
volume = {105},
number = {1},
pages = {e213738},
pmid = {40460337},
issn = {1526-632X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; *Telemedicine ; Wearable Electronic Devices ; Videoconferencing ; Digital Technology ; *Biomedical Technology ; Monitoring, Physiologic/methods ; Digital Health ; },
abstract = {Current care and research pathways for amyotrophic lateral sclerosis (ALS) primarily rely on regularly scheduled visits to specialized centers. These visits provide intermittent clinical information to health care professionals and require patients to travel to the clinic. Digital health technologies enable continuous data collection directly from the patient's home, bringing new opportunities for personalized, timely care and a refined assessment of disease severity in clinical trials. In this review, we summarize the state of the art in digital health technologies for remote monitoring of patients with ALS, ranging from televisits through videoconferencing to sensor-based wearable devices. We explore how these technologies can benefit clinical care and advance treatment development. Despite significant progress, real-world adoption of these technologies remains limited. An overview is provided of the key barriers hindering their widespread implementation and the opportunities to advance the field. Significantly, there is an urgent need for harmonization across stakeholders through consensus guidelines and consortia. These efforts are essential to accelerate progress and harness the full potential of digital health technologies to better meet the needs of patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/diagnosis
*Telemedicine
Wearable Electronic Devices
Videoconferencing
Digital Technology
*Biomedical Technology
Monitoring, Physiologic/methods
Digital Health

@article {pmid40463912,
year = {2025},
author = {Liu, T and Sun, W and Guo, S and Yuan, Z and Zhu, M and Lu, J and Chen, T and Qu, Y and Feng, C and Yang, T},
title = {Role of mitochondrial quality control in neurodegenerative disease progression.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1588645},
pmid = {40463912},
issn = {1662-5102},
abstract = {Neurodegenerative diseases are a diverse group of neurological disorders, in which abnormal mitochondrial function is closely associated with their development and progression. This has generated significant research interest in the field. The proper functioning of mitochondria relies on the dynamic regulation of the mitochondrial quality control system. Key processes such as mitochondrial biogenesis, mitophagy, and mitochondrial dynamics (division/fusion) are essential for maintaining this balance. These processes collectively govern mitochondrial function and homeostasis. Therefore, the mitochondrial quality control system plays a critical role in the onset and progression of neurodegenerative diseases. This article provides a concise overview of the molecular mechanisms involved in mitochondrial biogenesis, mitophagy, and mitochondrial dynamics, explores their interactions, and summarizes current research progress in understanding the mitochondrial quality control system in the context of neurodegenerative diseases.},
}

@article {pmid40464332,
year = {2025},
author = {Naim, A and Farooqui, AM and Badruddeen, and Khan, MI and Akhtar, J and Ahmad, A and Islam, A},
title = {The Role of Kinases in Neurodegenerative Diseases: From Pathogenesis to Treatment.},
journal = {The European journal of neuroscience},
volume = {61},
number = {11},
pages = {e70156},
doi = {10.1111/ejn.70156},
pmid = {40464332},
issn = {1460-9568},
mesh = {Humans ; *Neurodegenerative Diseases/enzymology/drug therapy/metabolism ; Animals ; *Protein Kinases/metabolism ; Protein Kinase Inhibitors/therapeutic use ; },
abstract = {Neurodegenerative diseases are characterized by progressive neuronal loss and dysfunction, with protein kinases playing crucial roles in their pathogenesis. This article explores the involvement of protein kinases in these disorders, focusing on their contributions to disease mechanisms, potential as therapeutic targets and challenges in developing effective treatments. In Alzheimer's disease, kinases such as CDK5, GSK3β and MARK4 are implicated in tau hyperphosphorylation and the formation of neurofibrillary tangles. Kinases also regulate amyloid-β processing and plaque formation. In Parkinson's disease, LRRK2, PINK1 and other kinases contribute to α-synuclein pathology, mitochondrial dysfunction and neuroinflammation. LRRK2 inhibitors and PROTACs have shown promise in preclinical models. Huntington's disease involves altered kinase activity, with CK2, GSK3 and MAPK pathways influencing mutant huntingtin toxicity and aggregation. Kinases are also implicated in less common neurodegenerative diseases, such as ALS and spinocerebellar ataxias. Despite the therapeutic potential of targeting kinases, challenges remain, including the complexity of kinase networks, blood-brain barrier permeability and the lack of robust biomarkers. Emerging technologies, such as covalent inhibitors, targeted protein degradation and combination therapies, offer new avenues for addressing these challenges and developing more effective treatments for neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/enzymology/drug therapy/metabolism
Animals
*Protein Kinases/metabolism
Protein Kinase Inhibitors/therapeutic use

@article {pmid40464500,
year = {2025},
author = {Dedoni, S and Avdoshina, V and Olianas, MC and Onali, P},
title = {Role of Lysophosphatidic Acid in Neurological Diseases: From Pathophysiology to Therapeutic Implications.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {30},
number = {5},
pages = {28245},
doi = {10.31083/FBL28245},
pmid = {40464500},
issn = {2768-6698},
mesh = {Humans ; *Lysophospholipids/metabolism ; *Nervous System Diseases/physiopathology/metabolism/drug therapy ; Animals ; Receptors, Lysophosphatidic Acid/metabolism ; Signal Transduction ; },
abstract = {Lysophosphatidic acid (LPA), a bioactive lipid molecule, has been identified as a critical regulator of several cellular processes in the central nervous system, with significant impacts on neuronal function, synaptic plasticity, and neuroinflammatory responses. While Alzheimer's disease, Multiple Sclerosis, and Parkinson's disease have garnered considerable attention due to their incidence and socioeconomic significance, many additional neurological illnesses remain unclear in terms of underlying pathophysiology and prospective treatment targets. This review synthesizes evidence linking LPA's function in neurological diseases such as traumatic brain injury, spinal cord injury, cerebellar ataxia, cerebral ischemia, seizures, Huntington's disease, amyotrophic lateral sclerosis, Hutchinson-Gilford progeria syndrome, autism, migraine, and human immunodeficiency virus (HIV)-associated complications Despite recent advances, the specific mechanisms underlying LPA's actions in various neurological disorders remain unknown, and further research is needed to understand the distinct roles of LPA across multiple disease conditions, as well as to investigate the therapeutic potential of targeting LPA receptors in these pathologies. The purpose of this review is to highlight the multiple functions of LPA in the aforementioned neurological diseases, which frequently share the same poor prognosis due to a scarcity of truly effective therapies, while also evaluating the role of LPA, its receptors, and signaling as promising actors for the development of alternative therapeutic strategies to those proposed today.},
}

Humans
*Lysophospholipids/metabolism
*Nervous System Diseases/physiopathology/metabolism/drug therapy
Animals
Receptors, Lysophosphatidic Acid/metabolism
Signal Transduction

@article {pmid40464816,
year = {2025},
author = {Savran, Z and Baltaci, SB and Aladag, T and Mogulkoc, R and Baltaci, AK},
title = {Vitamin D and Neurodegenerative Diseases Such as Multiple Sclerosis (MS), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS): A Review of Current Literature.},
journal = {Current nutrition reports},
volume = {14},
number = {1},
pages = {77},
pmid = {40464816},
issn = {2161-3311},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Vitamin D/metabolism ; Multiple Sclerosis ; Alzheimer Disease ; Parkinson Disease ; Receptors, Calcitriol/metabolism ; Amyotrophic Lateral Sclerosis ; Oxidative Stress/drug effects ; Animals ; Cholecalciferol ; },
abstract = {PURPOSE OF REVIEW: This review explores the role of Vitamin D3 and its derivatives as inhibitors of pathological metabolic modifications in neurodegenerative diseases. The manuscript investigates how Vitamin D3 impacts neuronal calcium regulation, antioxidative pathways, immunomodulation, and neuroprotection during detoxification, beyond its known functions in intestinal, bone, and kidney calcium and phosphorus absorption, as well as bone mineralization.

RECENT FINDINGS: Recent studies have highlighted the synthesis of the active metabolite 1,25(OH)2D3 (vitamin D) in glial cells via the hydroxylation process of CY-P24A1, an enzyme in the cytochrome P450 system in the brain. The effects of vitamin D occur through the vitamin D receptor (VDR), a nuclear steroid receptor, which has been identified in various brain regions, including the cerebellum, thalamus, hypothalamus, basal ganglia, hippocampus, olfactory system, temporal, and orbital regions. Neurodegeneration is primarily associated with oxidative stress, protein aggregation, neuroinflammation, mitochondrial dysfunction, apoptosis, and autophagy changes, all of which Vitamin D and VDR are believed to influence. Vitamin D and VDR are recognized as both environmental and genetic factors in the etiopathogenesis of neurodegenerative diseases such as Multiple Sclerosis (MS), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS). A deficiency in Vitamin D is postulated to have detrimental effects on the brain and other diseases throughout various stages of life. This review consolidates findings from clinical and experimental studies, as well as past publications, focusing on the implications of Vitamin D deficiency in these neurodegenerative conditions. Current articles published in PubMed were extensively considered for this review.},
}

Humans
*Neurodegenerative Diseases/metabolism/drug therapy
*Vitamin D/metabolism
Multiple Sclerosis
Alzheimer Disease
Parkinson Disease
Receptors, Calcitriol/metabolism
Amyotrophic Lateral Sclerosis
Oxidative Stress/drug effects
Animals
Cholecalciferol

@article {pmid40468389,
year = {2025},
author = {Rummens, J and Da Cruz, S},
title = {RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.},
journal = {Molecular neurodegeneration},
volume = {20},
number = {1},
pages = {64},
pmid = {40468389},
issn = {1750-1326},
support = {G064721N//Fonds Wetenschappelijk Onderzoek/ ; 1S15218N//Fonds Wetenschappelijk Onderzoek/ ; 962700//Muscular Dystrophy Association/ ; SAO-FRA 20230035//Alzheimer's Research Foundation/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; *Frontotemporal Dementia/metabolism/pathology/genetics ; *RNA-Binding Proteins/metabolism/genetics ; Animals ; DNA-Binding Proteins/metabolism ; RNA-Binding Protein FUS/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative disorders with overlapping clinical, genetic and pathological features. A large body of evidence highlights the critical role of RNA-binding proteins (RBPs) - in particular TAR DNA-binding protein 43 (TDP-43) and Fused in sarcoma (FUS) - in the pathogenesis of these diseases. These RBPs normally regulate various key aspects of RNA metabolism in the nervous system (by assembling into transient biomolecular condensates), but undergo cytoplasmic mislocalization and pathological aggregation in ALS and FTD. Furthermore, emerging evidence suggests that RBP-containing aggregates may propagate through the nervous system in a prion-like manner, driving the progression of these neurodegenerative diseases. In this review, we summarize the genetic and neuropathological findings that establish RBP dysfunction as a central theme in ALS and FTD, and discuss the role of disease-associated RBPs in health and disease. Furthermore, we review emerging evidence regarding the prion-like properties of RBP pathology, and explore the downstream mechanisms that drive neurodegeneration. By unraveling the complex role of RBPs in ALS and FTD, we ultimately aim to provide insights into potential avenues for therapeutic intervention in these incurable disorders.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
*Frontotemporal Dementia/metabolism/pathology/genetics
*RNA-Binding Proteins/metabolism/genetics
Animals
DNA-Binding Proteins/metabolism
RNA-Binding Protein FUS/metabolism

@article {pmid40470490,
year = {2025},
author = {Ren, S and Che, X and Hu, S and Feng, X and Zhang, J and Shi, P},
title = {The effect of exercise intervention on amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1499407},
pmid = {40470490},
issn = {1664-2295},
abstract = {OBJECTIVE: Quantitative evaluation of the effect of exercise intervention in amyotrophic lateral sclerosis (ALS).

METHODS: The CNKI, WOS, PubMed, and Scopus databases were searched by computer, and randomized controlled trials (RCTs) of exercise intervention in ALS were screened out according to the inclusion and exclusion criteria of the PICOS principle. Stata 12.0 software was used for statistical analysis.

RESULTS: A total of 12 RCTs including 430 participants were included. Meta-analysis results show that exercise intervention can significantly improve the overall function, walking test (WT) distance and maximum expiratory pressure (MEP) of ALS patients (p < 0.05). However, exercise interventions did not show significant effects on fatigue, maximum inspiratory pressure (MIP), forced vital capacity (FVC), and peak expiratory flow (PEF) in ALS patients (p > 0.05). Subgroup analysis showed that resistance exercise is the most effective intervention for improving the function of ALS patients, while aerobic exercise is the most effective intervention for improving FVC in ALS patients.

CONCLUSION: Exercise intervention in ALS has a positive effect, but due to the small number of included studies and possible heterogeneity, risk of bias and sensitivity issues, further research is needed.},
}

@article {pmid40473505,
year = {2026},
author = {Song, W and Huang, Q and Jiang, Z},
title = {Clinical efficacy of athletic taping-assisted physiotherapy for plantar fasciitis: A systematic evaluation and meta-analysis.},
journal = {Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons},
volume = {32},
number = {1},
pages = {11-25},
doi = {10.1016/j.fas.2025.05.013},
pmid = {40473505},
issn = {1460-9584},
mesh = {Humans ; *Fasciitis, Plantar/therapy ; *Athletic Tape ; Randomized Controlled Trials as Topic ; Pain Measurement ; Treatment Outcome ; *Physical Therapy Modalities ; },
abstract = {BACKGROUND: Plantar fasciitis is a common sports injury with long-term chronic pain in the heel as the main symptom, and athletic taping has achieved certain therapeutic effects to improve it, but the clinical efficacy of the problem is still controversial, which was evaluated by Meta-analysis to evaluate the clinical efficacy of the athletic taping technique on patients with plantar fasciitis.

METHODS: The Cochrane Library, Embase, PubMed, Web of Science, CNKI, Wanfang, and Vip databases were searched by computer for randomized controlled trial on the clinical efficacy of exercise taping in patients with PF from the time of construction to 1 September 2024, and the PRISMA 2020 checklist was strictly followed. Quality was assessed using the cochrane 2.0 randomized controlled trials scale by two independent reviewers. Endings were meta-analysis using RevMan 5.4.1 analysis software to analyse the data.

RESULTS: Eleven randomized controlled trial with a total of 395 patients were included. On VAS scores, KT effectively reduced VAS pain scores (MD=-0.79,95 % CI -1.10,-0.48, P < 0.00001); on AOFAS scores, KT improved AOFAS function scores (MD=6.58, 95 % CI 5.03,8.13, P < 0.00001) and the results remained consistent across intervention durations; on plantar fascia thickness measurements, KT significantly reduced plantar fascia thickness (MD=-0.33, 95 % CI -0.56,-0.10, P = 0.005); on BBS scores, KT significantly improved BBS scores [MD= 4.75, 95 % CI (3.17, 6.32), P < 0.00001]; on FFI-FPS scores, KT effectively improved FFI-FPS scores [MD = -2.59, 95 % CI (-3.50, -1.69), P < 0.00001]; on FFI-FDS scores, there was a significant improvement on FFI-FDS scores; on FFI-ALS scores, KT had a significant improvement on the FFI-ALS score had a significant effect [MD= -11.03, 95 % CI (-14.79, -7.27), P < 0.00001]; and on VAS scores after follow-up, the pain relief effect was sustained (MD=-1.03, 95 % CI -1.21, -0.85, P < 0.00001).

CONCLUSION: Based on the available evidence, preliminary analyses suggest that KT combined with conventional rehabilitation may have some advantages in improving pain, ankle-hindfoot function, and plantar fascia thickness in patients with plantar fasciitis, and some of the efficacy is short-term sustained. However, due to the heterogeneity and sample size of the included studies, the above conclusions need to be further validated by more high-quality studies.},
}

Humans
*Fasciitis, Plantar/therapy
*Athletic Tape
Randomized Controlled Trials as Topic
Pain Measurement
Treatment Outcome
*Physical Therapy Modalities

@article {pmid40476303,
year = {2025},
author = {Mustafa, MA and Bansal, P and Pallavi, MS and Panigrahi, R and Nathiya, D and Kumar, S and Al-Hasnaawei, S and Chauhan, AS and Singla, S},
title = {Exploring the Role of NLRP3 in Neurodegeneration: Cutting-Edge Therapeutic Strategies and Inhibitors.},
journal = {Developmental neurobiology},
volume = {85},
number = {3},
pages = {e22982},
doi = {10.1002/dneu.22982},
pmid = {40476303},
issn = {1932-846X},
mesh = {*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists & inhibitors ; Humans ; Animals ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Inflammasomes/metabolism ; *Neuroprotective Agents/pharmacology ; },
abstract = {Inflammasomes, particularly the NLRP3 inflammasome, play a pivotal role in mediating neuroinflammation in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Huntington's disease (HD). Recent findings indicate that the activation of the NLRP3 inflammasome in microglia and astrocytes triggers the release of pro-inflammatory cytokines, including IL-1β and IL-18, which contribute to chronic inflammation and neuronal damage. This process accelerates neurodegeneration and exacerbates disease progression. Misfolded protein aggregates, mitochondrial dysfunction, and oxidative stress are key factors in the pathological activation of the NLRP3 inflammasome in these diseases. Recent studies have highlighted that targeting the NLRP3 inflammasome, either through direct inhibitors like MCC950 or natural compounds such as oridonin and β-hydroxybutyrate, shows promise in mitigating neuroinflammation and protecting neuronal integrity. These inhibitors have demonstrated neuroprotective effects in animal models of AD, PD, and MS, presenting a new therapeutic approach for halting disease progression. However, the complexity of NLRP3 regulation requires further investigation to balance its inflammatory and protective roles. This review examines the recent advancements in NLRP3 inflammasome research and discusses potential strategies for modulating inflammasome activity to slow or prevent the progression of neurodegenerative diseases.},
}

*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists & inhibitors
Humans
Animals
*Neurodegenerative Diseases/metabolism/drug therapy
*Inflammasomes/metabolism
*Neuroprotective Agents/pharmacology

@article {pmid40479789,
year = {2025},
author = {Hosseini, MM and Masoumian Hosseini, ST and Haghighi, E and Qayumi, K and Ebrahimipour, H and Pourabbasi, A and Koohpaei, A and Alizadeh, M and Shafiei, Z},
title = {The revolutionary impact of 6G technology on empowering health and building a smart society: A scoping review.},
journal = {Computers in biology and medicine},
volume = {194},
number = {},
pages = {110496},
doi = {10.1016/j.compbiomed.2025.110496},
pmid = {40479789},
issn = {1879-0534},
mesh = {Humans ; *Wireless Technology ; Telemedicine ; Delivery of Health Care ; Artificial Intelligence ; Computer Security ; },
abstract = {OBJECTIVE: This scoping review investigates the potential of 6G technology in healthcare, particularly in smart city settings, focusing on its enhanced data capabilities, AI's role in healthcare optimization, infrastructure support, interoperability, quality standards, and privacy and security concerns.

PATIENTS AND METHODS: The scoping review followed the Arksey and O'Malley framework, with Levac et al.'s methodological advancements. The review team searched academic databases like PubMed/Medline, SCOPUS, Embase, Web of Sciences, and IEEE Xplore. They also explored grey literature sources like Google Scholar, OpenGrey, and Web of Science Conference Proceedings. A search strategy was developed, and 145 studies were selected from an initial pool of 9835 records from 2010 to 2025. The review categorized 145 studies into three phases, focusing on deploying 6G technology in healthcare, the infrastructure required, and ethical considerations related to the technology's ethical implications.

RESULT: Phase one focused on advancements like real-time imaging, performing medical procedures remotely, using predictive tools to analyze data, and providing care tailored to individual patients. Phase two examined how the next generation of wireless technology (6G) could interact with communication systems, including techniques to handle large amounts of data (massive MIMO) and using extremely high-frequency signals (terahertz communications) to transfer information faster. Phase three explored ethical concerns about applying 6G technology, such as systems that make decisions based on user intentions (intent-driven management) and organizing information around data-based designs (data-driven architecture). The review highlights how 6G technology could revolutionize patient care and medical services by enabling faster data transfers, reducing delays, increasing system capacity, and incorporating artificial intelligence.

CONCLUSION: The scoping review shows the capability of the transformative potential of 6G technology, particularly in healthcare and urban development, emphasizing its enhanced data transfer speeds, reduced latency, and increased capacity that can significantly improve patient care through better remote monitoring, security, and telemedicine services. It stresses the vital role of policymakers in guiding the development of 6G infrastructure, ensuring effective spectrum allocation, and implementing robust security measures while addressing health and electromagnetic exposure concerns. Policymakers are urged to adopt security-by-design principles, adhere to international standards, and foster collaboration among academia, industry, and government to drive innovation and ensure the responsible deployment of 6G technology. By stimulating research and establishing clear performance metrics, they can facilitate continuous improvement and adaptation, ultimately benefiting society as a whole. The review concludes that strategic policy formulation is essential for maximizing the advantages of 6G technology, leading to more intelligent, productive, and sustainable societal frameworks.},
}

Humans
*Wireless Technology
Telemedicine
Delivery of Health Care
Artificial Intelligence
Computer Security

@article {pmid40482451,
year = {2025},
author = {Attiq, A and Afzal, S and Raman, H and Ahmad, W},
title = {Neuroinflammation to neurodegeneration: Boulevard of broken nerves.},
journal = {International immunopharmacology},
volume = {161},
number = {},
pages = {115015},
doi = {10.1016/j.intimp.2025.115015},
pmid = {40482451},
issn = {1878-1705},
mesh = {Humans ; Animals ; *Neuroinflammatory Diseases/immunology/drug therapy/therapy ; *Neurodegenerative Diseases/immunology/drug therapy/therapy ; *Anti-Inflammatory Agents/therapeutic use ; Cytokines/metabolism ; },
abstract = {Neuroinflammation is caused by various factors, such as the activation of glial cells, the excessive release of chemokines and cytokines, and the accumulation of blood cells in the brain parenchyma. The inflammatory processes occur in acute and chronic phases, with traumatic brain injuries triggering the release of neurotoxins from CNS-specific glial cells. Furthermore, activation of microglia, astrocytes, and mast cells worsens the situation by producing pro-inflammatory cytokines, chemokines and glia maturation factors. Chronic activation of astroglia and microglial cells promotes loss of neurons, memory, and impaired learning capacity, leading to neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. These implications have led to a rational search for inflammatory druggable targets. Based on various preclinical and clinical studies, NSAIDs (aspirin, ibuprofen, diclofenac, and mefenamic acid), SSRIs (fluoxetine and sertraline), antipsychotics (risperidone), corticosteroids (dexamethasone), antidiabetics (metformin and rosiglitazone), and statins (simvastatin and atorvastatin) have exhibited promising results. These drugs have anti-inflammatory and neuromodulation activities that enhance neuroplasticity and effectively manage neurodegenerative symptoms. In addition, non-pharmacological interventions such as art creation and physical exercise have been linked with improving neural development and stimulating the production of anti-inflammatory cytokines, which can attenuate disease progression and promote synaptic plasticity. Hence, it is imperative to understand the complex interplay between glial cells, inflammatory signalling and neural pathways. We reviewed the interconnected pathways between neuroinflammation and neurodegeneration. Moreover, recommendations for pharmacological and non-pharmacological interventions to address these issues are discussed herein.},
}

Humans
Animals
*Neuroinflammatory Diseases/immunology/drug therapy/therapy
*Neurodegenerative Diseases/immunology/drug therapy/therapy
*Anti-Inflammatory Agents/therapeutic use
Cytokines/metabolism

@article {pmid40485888,
year = {2025},
author = {Liu, Y and Ren, Y and Song, P},
title = {Traditional Chinese medicine for intractable and rare diseases: Research progress and future strategies.},
journal = {Intractable & rare diseases research},
volume = {14},
number = {2},
pages = {109-121},
pmid = {40485888},
issn = {2186-3644},
abstract = {Rare diseases have become a global public health challenge due to their low prevalence, difficult diagnosis, and limited treatment options. Intractable diseases are more common but often involve complex mechanisms, treatment with limited efficacy, and high medical costs, placing a heavy burden on patients and healthcare systems. In recent years, traditional Chinese medicine (TCM) has demonstrated unique advantages in the treatment of intractable and rare diseases and has gradually become an important complementary treatment. The current work is a systematic review of the progress of clinical and experimental research on TCM in typical rare diseases such as amyotrophic lateral sclerosis (ALS), systemic lupus erythematosus (SLE), mitochondrial encephalomyopathy, aplastic anemia (AA), and Wilson's disease (WD). It focuses on the multi-target therapeutic mechanisms of key Chinese herbal compound formulas, including immune regulation, antioxidative stress, and neuroprotection. The core TCM theories of "syndrome differentiation", "different treatments for the same disease" and the "same treatment for different diseases" are also discussed in the context of personalized medicine. In recent years, China has continuously promoted the development of TCM through a series of national plans and supportive policies, such as the 14th Five-Year Plan for TCM development, funding for key special projects, expedited approval pathways, and expanded coverage by medical insurance. These efforts have provided strong support for the clinical translation of TCM and technological innovation in the field of intractable and rare diseases. Notwithstanding the encouraging advances, the field of Chinese medicine continues to grapple with numerous challenges. In the future, the enhancement of mechanistic studies and quality multicenter clinical trials needs to be promoted while further enhancing policy support and international collaboration to substantiate the scientific basis and clinical value of TCM in the prevention and treatment of intractable and rare diseases.},
}

@article {pmid40488544,
year = {2025},
author = {Benzo-Iglesias, MJ and Rocamora-Pérez, P and Valverde-Martínez, MLÁ and García-Luengo, AV and Benzo-Iglesias, PM and López-Liria, R},
title = {Efficacy of respiratory muscle training in improving pulmonary function and survival in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Therapeutic advances in respiratory disease},
volume = {19},
number = {},
pages = {17534666251346095},
pmid = {40488544},
issn = {1753-4666},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/mortality/therapy/diagnosis ; *Respiratory Muscles/physiopathology ; *Breathing Exercises/adverse effects/methods ; Randomized Controlled Trials as Topic ; Quality of Life ; Muscle Strength ; *Lung/physiopathology ; Treatment Outcome ; Recovery of Function ; Male ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, loss of function, and ultimately death due to respiratory failure. Due to the lethal prognosis of ALS, respiratory muscle training has been proposed as a potentially beneficial intervention.

OBJECTIVES: To systematically review the efficacy of respiratory muscle training on lung function and respiratory muscle strength in ALS patients.

DESIGN: A systematic review and meta-analysis of randomized controlled trials.

DATA SOURCES AND METHODS: Articles published in PubMed, PEDro, Scopus, and Web of Science databases up to July 2024. The Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement guideline was followed. Included studies had (1) ALS patients, (2) respiratory muscle training, (3) physical exercise, usual care or no intervention were provided as a comparison group, (4) assessments of lung function, respiratory muscle strength, quality of life, survival, fatigue, and functional capacity outcome measures, and (5) a randomized controlled trial design. Methodological quality was analyzed using the PEDro scale, and risk of bias with the Cochrane Collaboration Risk of Bias Tool. Meta-analyses were performed with Review Manager software.

RESULTS: Five randomized controlled trials with 170 participants were included. The results showed that respiratory muscle training improved muscle strength, particularly maximum expiratory and inspiratory pressures. One study suggested inspiratory muscle training as a survival predictor in ALS patients. No significant effects were observed in forced vital capacity or quality of life. No adverse effects were reported.

CONCLUSION: Respiratory muscle training improves ventilatory function, particularly respiratory muscle strength, in people with ALS. While evidence is limited, it shows promise as an adjuvant therapy to enhance quality of life and survival. It has been registered in the PROSPERO (CRD42024568235).},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/mortality/therapy/diagnosis
*Respiratory Muscles/physiopathology
*Breathing Exercises/adverse effects/methods
Randomized Controlled Trials as Topic
Quality of Life
Muscle Strength
*Lung/physiopathology
Treatment Outcome
Recovery of Function
Male

@article {pmid40488810,
year = {2025},
author = {Kulkarni, SR and Thokchom, B and Abbigeri, MB and Bhavi, SM and Singh, SR and Metri, N and Yarajarla, RB},
title = {The role of L-DOPA in neurological and neurodegenerative complications: a review.},
journal = {Molecular and cellular biochemistry},
volume = {480},
number = {10},
pages = {5221-5242},
pmid = {40488810},
issn = {1573-4919},
mesh = {Humans ; *Levodopa/therapeutic use/pharmacokinetics/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism/pathology ; Animals ; Blood-Brain Barrier/metabolism ; *Parkinson Disease/drug therapy/metabolism ; },
abstract = {L-DOPA remains a cornerstone treatment for Parkinson's disease and is increasingly recognized for its role in various neurological and neurodegenerative disorders. As a direct precursor to dopamine, L-DOPA is synthesized from L-tyrosine through the action of tyrosine hydroxylase and is subsequently converted into dopamine via aromatic L-amino acid decarboxylase. Its ability to cross the blood-brain barrier (BBB) makes it a crucial therapeutic agent for restoring dopaminergic neurotransmission, thereby influencing motor function, cognition, and neuroprotection. Beyond Parkinson's, L-DOPA's therapeutic potential extends to neurodegenerative conditions such as Alzheimer's disease, Huntington's disease, multiple sclerosis, Lewy body dementia, and amyotrophic lateral sclerosis, where dopamine modulation plays a critical role. Furthermore, L-DOPA has demonstrated efficacy in neurological disorders including epilepsy, peripheral neuropathy, cerebrovascular diseases, and traumatic brain injury, suggesting broader neurobiological applications. However, long-term use is associated with challenges such as motor fluctuations, dyskinesias, and loss of therapeutic efficacy due to progressive neurodegeneration and alterations in dopaminergic pathways. Recent advancements in drug delivery systems, combination therapies, and nanotechnology, including plant-derived carbon dots, offer promising strategies to enhance L-DOPA's effectiveness while mitigating its limitations. This comprehensive review explores L-DOPA's synthesis, pharmacokinetics, mechanism of action, and its evolving role in neurological diseases, while highlighting ongoing challenges and future directions for optimizing its clinical application.},
}

Humans
*Levodopa/therapeutic use/pharmacokinetics/pharmacology
*Neurodegenerative Diseases/drug therapy/metabolism/pathology
Animals
Blood-Brain Barrier/metabolism
*Parkinson Disease/drug therapy/metabolism

@article {pmid40493155,
year = {2025},
author = {Kang, A and Qiao, Y and Pan, S and Yan, F and Chen, H and Bai, Y},
title = {From RIPK1 to Necroptosis: Pathogenic Mechanisms in Neurodegenerative Diseases.},
journal = {Neurochemical research},
volume = {50},
number = {3},
pages = {194},
pmid = {40493155},
issn = {1573-6903},
support = {24JRRA346//Natural Science Foundation of Gansu Province/ ; CY2023-QN-B03//"Cuiying Science and Technology Program" of the Second Hospital of Lanzhou University/ ; (23)0207//Foundation for International Medical Exchanges/ ; (23)1263//China Health Promotion Foundation/ ; },
mesh = {Humans ; *Necroptosis/physiology/drug effects ; *Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/drug therapy ; Animals ; Signal Transduction/physiology ; },
abstract = {Receptor-interacting protein kinase 1 (RIPK1)-mediated necroptosis, a newly identified mode of regulated cell death, represents a significant pathogenic mechanism in multiple neurodegenerative disorders. Substantial experimental evidence indicates that RIPK1 regulates necroptotic cell death pathways in both neuronal and glial cell populations through activation of the canonical RIPK3-MLKL signaling cascade, thereby exacerbating neuroinflammatory responses and accelerating neurodegenerative progression. The pathological relevance of this molecular pathway has been extensively validated across multiple major neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Pharmacological interventions targeting RIPK1 or its downstream effectors-particularly RIPK3 and MLKL-have demonstrated significant efficacy in mitigating disease-associated pathological manifestations. This highlights the RIPK1 signaling axis as a promising therapeutic target for neuroprotective strategies. Consequently, thorough investigation of RIPK1-mediated necroptosis in neurodegenerative settings holds considerable translational potential. Such inquiry deepens mechanistic understanding of disease pathogenesis while accelerating the advancement of innovative therapeutic approaches with direct clinical relevance.},
}

Humans
*Necroptosis/physiology/drug effects
*Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
*Neurodegenerative Diseases/metabolism/pathology/drug therapy
Animals
Signal Transduction/physiology

@article {pmid40495142,
year = {2025},
author = {Matting, L and Pfeifer, K and Sudeck, G and Jung, A and Langhirt, F and Geidl, W},
title = {Physical activity promotion in physical therapy, exercise therapy and other movement-based therapies: a scoping review and content analysis of intervention studies and theoretical works.},
journal = {The international journal of behavioral nutrition and physical activity},
volume = {22},
number = {1},
pages = {72},
pmid = {40495142},
issn = {1479-5868},
mesh = {Humans ; *Exercise ; *Exercise Therapy/methods ; *Health Promotion/methods ; *Physical Therapy Modalities ; *Noncommunicable Diseases/therapy ; },
abstract = {BACKGROUND: Movement-based therapists, including physical, exercise, and sport therapists, play a key role in promoting physical activity in individuals with non-communicable diseases. However, no clear consensus exists on effective intervention approaches. This scoping review examines available intervention studies and theoretical works for physical activity promotion in movement-based therapy. METHODS: In accordance with Colquhoun et al.‘s framework and PRISMA-ScR guidelines, we systematically searched PubMed, Scopus, Web of Science, and PsycINFO until March 31, 2024. Eligible records described physical activity-promoting concepts including interventional studies and theoretical works applicable in movement-based therapies for individuals with non-communicable diseases. Data extraction covered assessment, therapeutic content, didactic-methodological principles, and theoretical underpinnings. Interventions were categorized based on behavior change techniques (BCTs), the behavior change wheel, and a clinical reasoning model for clients behavior change. Network analysis explored relationships between therapeutic content and didactic-methodological principles. RESULTS: Fifty-seven records met inclusion criteria; 77% were intervention studies, and 23% were theoretical works. Most concepts originated from orthopedics/rheumatology (23%), neurology (21%), and oncology (9%), while 12% were generic concepts. Across concepts, 66 biopsychosocial assessment instruments and 60 BCTs were applied (Median BCTs per concept: 11.5, range: 4–37). Key didactic-methodological principles included tailoring/individualization (n = 47), active participation (n = 39), collaborative communication (n = 21), and patient self-responsibility and independence (n = 14). Least mentioned was facilitating positive movement experiences and enjoyment of physical activity (n = 3). Network analysis identified action planning, goal setting, and feedback as central BCTs. CONCLUSION: This review provides an overview of 57 physical activity promotion concepts used in movement-based therapies for individuals with non-communicable diseases. Findings reveal considerable heterogeneity, highlighting diverse strategies used by movement-based therapists to influence physical activity behavior. TRIAL REGISTRATION: Open Science Framework (OSF), December 23, 2022 (DOI: https://doi.org/10.17605/OSF.IO/AXZSJ).},
}

Humans
*Exercise
*Exercise Therapy/methods
*Health Promotion/methods
*Physical Therapy Modalities
*Noncommunicable Diseases/therapy

@article {pmid40495464,
year = {2025},
author = {Majtan, T and Mijatovic, E and Petrosino, M},
title = {Understanding the Impact of Mutations in the Cystathionine Beta-Synthase Gene: Towards Novel Therapeutics for Homocystinuria.},
journal = {Molecular and cellular biology},
volume = {45},
number = {8},
pages = {327-342},
doi = {10.1080/10985549.2025.2511338},
pmid = {40495464},
issn = {1098-5549},
mesh = {Humans ; *Homocystinuria/genetics/drug therapy/enzymology ; *Cystathionine beta-Synthase/genetics/metabolism/chemistry ; Animals ; *Mutation ; Protein Folding ; Molecular Chaperones/therapeutic use ; },
abstract = {Protein misfolding and conformational instability drive protein conformational disorders, causing either accelerated degradation and loss-of-function, as in inherited metabolic disorders like lysosomal storage disorders, or toxic aggregation and gain-of-function, as in neurodegenerative diseases like Alzheimer's disease or amyotrophic lateral sclerosis. Classical homocystinuria (HCU), an inborn error of sulfur amino acid metabolism, results from cystathionine beta-synthase (CBS) deficiency. CBS regulates methionine conversion into metabolites critical for redox balance (cysteine, glutathione) and signaling (H2S). Pathogenic missense mutations in the CBS gene often impair folding, cofactor binding, stability or oligomerization rather than targeting the key catalytic residues of the CBS enzyme. Advances in understanding of CBS folding and assembly as well as CBS interactions with cellular proteostasis network offer potential for therapies using pharmacological chaperones (PCs), i.e., compounds facilitating proper folding, assembly or cellular trafficking. This review discusses progress in identifying PCs for HCU, including chemical chaperones, cofactors, and proteasome inhibitors. We outline future directions, focusing on high-throughput screening and structure-based drug design to develop CBS-specific PCs. These could stabilize mutant CBS, enhance its stability and restore activity, providing new treatments for HCU and possibly other conditions related to dysregulated CBS, such as cancer or Down's syndrome.},
}

Humans
*Homocystinuria/genetics/drug therapy/enzymology
*Cystathionine beta-Synthase/genetics/metabolism/chemistry
Animals
*Mutation
Protein Folding
Molecular Chaperones/therapeutic use

@article {pmid40498024,
year = {2025},
author = {Pisoni, L and Donini, L and Gagni, P and Pennuto, M and Ratti, A and Verde, F and Ticozzi, N and Mandrioli, J and Calvo, A and Basso, M},
title = {Barriers in the Nervous System: Challenges and Opportunities for Novel Biomarkers in Amyotrophic Lateral Sclerosis.},
journal = {Cells},
volume = {14},
number = {11},
pages = {},
pmid = {40498024},
issn = {2073-4409},
support = {MUR PNRR project iNEST - Interconnected Nord-Est Innovation Ecosystem (ECS00000043)//NextGenerationEU/ ; PERMEALS - PNRR-MAD-2022-12375731//Ministero della Salute/ ; CUP E53D23019700001, project "MYSTICALS"//European Union - Next Generation EU, Mission 4, Component 1/ ; RF-2016-02361616//Ministero della Salute/ ; EVTestInALS//AriSLA/ ; Aldo Ravelli Center for Neurotechnology and Experimental Brain Therapeutics//Università degli Studi di Milano/ ; MUR-PRIN 2022 project EV-PRINT 2022CS9H53//Next Generation EU/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/diagnosis ; *Biomarkers/metabolism ; Extracellular Vesicles/metabolism ; Animals ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by wide phenotypic heterogeneity. Despite efforts to carefully define and stratify ALS patients according to their clinical and genetic features, prognosis prediction still remains unreliable. Biomarkers that reflect changes in the central nervous system would be useful, but the physical impossibility of direct sampling and analysis of the nervous system makes them challenging to validate. A highly explored option is the identification of neuronal-specific markers that could be analyzed in peripheral biofluids. This review focuses on the description of the physical and biological barriers to the central nervous system and of the composition of biofluids in which ALS disease biomarkers are actively searched. Finally, we comment on already validated biomarkers, such as the neurofilament light chain, and show the potential of extracellular vesicles (EVs) and cell-free DNA as additional biomarkers for disease prediction.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/pathology/diagnosis
*Biomarkers/metabolism
Extracellular Vesicles/metabolism
Animals

@article {pmid40500504,
year = {2025},
author = {Niu, J and Verkhratsky, A and Butt, A and Yi, C},
title = {Oligodendroglia in Ageing and Age-Dependent Neurodegenerative Diseases.},
journal = {Advances in neurobiology},
volume = {43},
number = {},
pages = {363-405},
pmid = {40500504},
issn = {2190-5215},
mesh = {Humans ; *Oligodendroglia/pathology/physiology/metabolism ; *Neurodegenerative Diseases/pathology/physiopathology/metabolism ; *Aging/pathology/physiology ; Animals ; },
abstract = {The central nervous system is susceptible to gradual decline with age, affecting all types of glial cells in the process. Compared to other glial cells, the oligodendroglial lineage is highly vulnerable to ageing and undergoes significant characteristic changes that impact upon its structure and impair its physiological functions. Therefore, the ageing and degeneration of oligodendroglia become major risk factors for neurodegenerative diseases. During the age-related disease process, changes in oligodendroglia lead to a decline in their ability to regenerate myelin and respond to the aged microenvironment, which are closely linked to the pathogenesis of neurodegenerative diseases, facilitating the emergence of these diseases in older populations. In this chapter, we introduce the physiological changes of oligodendroglia during ageing and the related mechanisms and then summarise their pathophysiological contributions to age-related cognitive disorders. Finally, we discuss potential therapeutic strategies that target oligodendroglia for future research on neurodegenerative diseases.},
}

Humans
*Oligodendroglia/pathology/physiology/metabolism
*Neurodegenerative Diseases/pathology/physiopathology/metabolism
*Aging/pathology/physiology
Animals

@article {pmid40506782,
year = {2025},
author = {Briscoe, S and Martin Pintado, C and Sutcliffe, K and Melendez-Torres, GJ and Garside, R and Lawal, HM and Orr, N and Shaw, L and Thompson Coon, J},
title = {Evidence of inequities experienced by the rare disease community with respect to receipt of a diagnosis and access to services: a scoping review of UK and international evidence.},
journal = {Orphanet journal of rare diseases},
volume = {20},
number = {1},
pages = {303},
pmid = {40506782},
issn = {1750-1172},
support = {NIHR200695//National Institute for Health and Care Research/ ; },
mesh = {Humans ; *Health Services Accessibility ; *Healthcare Disparities ; *Rare Diseases/diagnosis ; United Kingdom ; },
abstract = {BACKGROUND: People with a rare disease find it difficult to obtain a diagnosis and access appropriate services. Evidence suggests that this can lead to health inequity amongst the rare disease community, i.e. systemic, unfair and avoidable differences in health opportunities and outcomes. This scoping review aims to identify and describe evidence on health inequities experienced by the rare disease community with regards to receipt of a diagnosis and access to health and social care services.

METHODS: We searched ASSIA, CINAHL, Embase, HMIC, MEDLINE and Social Policy and Practice for relevant studies. Studies were double screened at title and abstract and full-text using pre-specified inclusion criteria. As this research was commissioned by the UK National Institute for Health and Care Research Policy Research Programme, primary studies were limited to UK settings. These were supplemented with international systematic reviews. We also applied a 2010 date limit. Relevant data were extracted and presented narratively and tabulated.

RESULTS: One hundred thirty-six studies met the inclusion criteria, including 96 primary studies and 40 systematic reviews. The most frequently occurring rare diseases were motor neurone disease, cystic fibrosis and sickle cell disease. Seventeen types of inequity were identified: delayed diagnosis, lack of knowledge amongst clinicians, lack of information provision, limited services provision (across six different services), limited services for undiagnosed conditions, lack of care co-ordination; in addition, inequity was identified relating to place of residence, race/ethnicity, gender, socioeconomic status, age and disability.

CONCLUSION: This review has drawn attention to experiences of the rare disease community with respect to receipt of a diagnosis and access to services which are different to experiences in the general population, and within the rare disease community itself. Some of these experiences are clearly attributable to factors which are unfair, avoidable and systemic, particularly those which relate to specific groups in the rare disease community. Experiences relating to delayed diagnosis, lack of knowledge, information, care co-ordination and access to various services, also appeared to indicate inequity. These issues are less likely to be encountered with respect to more common diseases experienced in the general population.},
}

Humans
*Health Services Accessibility
*Healthcare Disparities
*Rare Diseases/diagnosis
United Kingdom

@article {pmid40508048,
year = {2025},
author = {Tolochko, C and Shiryaeva, O and Alekseeva, T and Dyachuk, V},
title = {Amyotrophic Lateral Sclerosis: Pathophysiological Mechanisms and Treatment Strategies (Part 2).},
journal = {International journal of molecular sciences},
volume = {26},
number = {11},
pages = {},
pmid = {40508048},
issn = {1422-0067},
mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/drug therapy/metabolism/therapy/etiology/pathology ; Humans ; Oxidative Stress/drug effects ; Animals ; Antioxidants/therapeutic use/pharmacology ; Motor Neurons/metabolism/pathology/drug effects ; Glutamic Acid/metabolism ; Neuroprotective Agents/therapeutic use ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease associated with damage to motor neurons and leading to severe muscle weakness and, eventually, death. Over the past decade, understanding of the key pathogenetic links of ALS, including glutamate-mediated excitotoxicity and oxidative stress, has significantly advanced. This review considers the recent evidence on molecular mechanisms of these processes, as well as the therapeutic strategies aimed at their modulation. Special attention is paid to antiglutamatergic and antioxidant drugs as approaches to the ALS pathogenetic therapy.},
}

*Amyotrophic Lateral Sclerosis/physiopathology/drug therapy/metabolism/therapy/etiology/pathology
Humans
Oxidative Stress/drug effects
Animals
Antioxidants/therapeutic use/pharmacology
Motor Neurons/metabolism/pathology/drug effects
Glutamic Acid/metabolism
Neuroprotective Agents/therapeutic use

@article {pmid40510202,
year = {2025},
author = {Li, L and Lv, L and Wang, Z and Liu, X and Wang, Q and Zhu, H and Jiang, B and Han, Y and Pan, X and Zhou, X and Ren, L and Chang, Z},
title = {From copper homeostasis to cuproptosis: a new perspective on CNS immune regulation and neurodegenerative diseases.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1581045},
pmid = {40510202},
issn = {1664-2295},
abstract = {Copper, an essential trace element for the human body, plays a key role in energy metabolism, mitochondrial respiration, redox reactions, and neural signal transmission. The recently proposed concept of "cuproptosis" has further revealed the unique status of copper in cellular regulation: when copper abnormally accumulates within cells, it can directly bind to the lipoylated proteins of the mitochondrial TCA cycle, triggering protein aggregation and metabolic disorders, ultimately leading to cell death. This form of cell death plays an important role in various neurodegenerative diseases of the central nervous system, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and stroke. This review summarizes recent research on the mechanisms of cuproptosis, providing new perspectives and a theoretical basis for understanding the pathogenesis of these neurodegenerative diseases.},
}

@article {pmid40511793,
year = {2026},
author = {Parks, ASE and Gotlib Conn, L and Amog, K and Bodmer, NS and King, JW and McLaren, AMR and Reid, M and Kishibe, T and Abrahao, A and Zinman, L and Sale, JEM},
title = {Age and life stage in the experience of amyotrophic lateral sclerosis: a scoping review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {27},
number = {1-2},
pages = {1-27},
doi = {10.1080/21678421.2025.2515914},
pmid = {40511793},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology ; Age Factors ; *Aging/psychology ; *Quality of Life/psychology ; Adult ; Middle Aged ; Aged ; Male ; Female ; },
abstract = {Objective: Understanding the experiences of people living with amyotrophic lateral sclerosis (plwALS) is necessary to appreciate their unique needs. Age and stage in the life course influence how illness is experienced; however, the extent to which age-specific complexities of living with ALS have been examined remains unexplored. This review aims to map the available evidence exploring age, age-graded role, or life-course transition with regards to the experience of ALS and to identify age-specific gaps in the literature. Methods: A scoping review guided by Joanna Briggs Institute methodology was undertaken. Eligible articles included peer-reviewed primary research studies, published in English from 2010 onward, investigating illness experience of adults with ALS with consideration for how age, age-graded roles, or life-course transitions influenced experience. Database sources included: Ovid's Medline, Embase, and PsycINFO; EBSCO CINAHL; and ProQuest Sociological Abstracts. Findings related to ALS experience and dimensions of age were summarized descriptively and categorized using qualitative content analysis. Results: Six thousand one hundred and eighty individual records were identified and screened. Forty-five articles, reporting 42 studies, were included. Findings regarding thoughts, feelings, or emotions of plwALS were most common and varied depending on whether they were in reference to chronological age or age-graded role. Despite the importance of life-course transitions for illness experience, they were not routinely considered. Conclusion: Numerous aspects of the experience of plwALS have been reported in reference to age; however, the significance of age-graded roles and life-course transitions warrants further examination. Recognition of age-related complexities of living with ALS will facilitate more personalized ALS care.},
}

Humans
*Amyotrophic Lateral Sclerosis/psychology
Age Factors
*Aging/psychology
*Quality of Life/psychology
Adult
Middle Aged
Aged
Male
Female

@article {pmid40513028,
year = {2025},
author = {Bromberg, MB},
title = {What Is in the Literature.},
journal = {Journal of clinical neuromuscular disease},
volume = {26},
number = {4},
pages = {176-183},
doi = {10.1097/CND.0000000000000526},
pmid = {40513028},
issn = {1537-1611},
mesh = {Humans ; *Motor Neuron Disease/therapy/diagnosis ; *Amyotrophic Lateral Sclerosis/therapy/diagnosis ; },
abstract = {This issue of What Is in the Literature focuses on articles over the past year on clinical aspects of motor neuron disease, including amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Disease-modifying treatment for ALS remains a challenge as 2 formal drug trials did not hold up to retesting. There are new thoughts based on a multistep model to partially explain why ALS develops relatively late in life. New information on fluid biomarkers, sex differences, efficacy of medical marijuana for common symptoms, and cognitive dysfunction are discussed. For the clinic, there are updated guidelines for multidisciplinary management. Other articles address how frequently the topic of sexual health is brought up in the clinic, and insights into how patients view end-of-life issues and quality of life when using tracheal ventilation. PLS has diagnostic challenges and practical aspects, which are reviewed.},
}

Humans
*Motor Neuron Disease/therapy/diagnosis
*Amyotrophic Lateral Sclerosis/therapy/diagnosis

@article {pmid40515812,
year = {2026},
author = {Jellinger, KA},
title = {Prevalence and impact of comorbidities in amyotrophic lateral sclerosis.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {133},
number = {3},
pages = {379-396},
pmid = {40515812},
issn = {1435-1463},
support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology ; Comorbidity ; Prevalence ; *Cardiovascular Diseases/epidemiology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of multifaceted nature and variable progression that poses considerable challenges to our understanding of its evolution and interplay with different comorbid conditions. The etiopathogenesis of ALS is still unexplained and multimorbidity is common, but its influence on the ALS susceptibility and disease course is a matter of discussion. This study using medical databases tries to find diseases associated with ALS and their impact on disease onset and progression. Diseases associated with the risk of ALS include diabetes mellitus, dyslipidemias and cardiovascular comorbidities that may play an important role in the prognosis of ALS. Hypometabolic disorders and cardiovascular diseases may have a protective effect on ALS incidence, while coronary heart disease and hypertension have a negative effect on disease progression. Other comorbidities include Parkinson disease, TDP-43 pathology, progressive supranuclear palsy, progressive aphasia, myasthenia gravis, cancer and autoimmune disorders, while there is no evidence for a shared genetic background of common risk variants in ALS and multiple sclerosis. Among non-motor manifestations of ALS, cognitive and behavioral impairments are important. Other comorbidities include sleep disorders, traumatic encephalopathy, sarcoidosis, prionopathies, schizophrenia, cervical spondylotic myelopathy, psoriasis and others. The tremendous heterogeneity of concomitant pathologies and comorbidities observed across the ALS spectrum may be caused by a complex interplay between genetic, pathogenetic, inflammatory and other risk factors that are still poorly understood. Further research should provide increasing insight into their relationship with motor system disorders in order to find better diagnostic tools and probable effective therapies for these disease-modifying comorbidities.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology
Comorbidity
Prevalence
*Cardiovascular Diseases/epidemiology

@article {pmid40516772,
year = {2025},
author = {Rawat, E and Sharma, S and Vyas, S and Alsaidan, OA and Kapoor, DU and Prajapati, BG},
title = {Advances in alginate-based nanoformulations: Innovative and effective strategies for targeting and treating brain disorders.},
journal = {International journal of pharmaceutics},
volume = {681},
number = {},
pages = {125851},
doi = {10.1016/j.ijpharm.2025.125851},
pmid = {40516772},
issn = {1873-3476},
mesh = {*Alginates/chemistry/administration & dosage ; Humans ; *Brain Diseases/drug therapy ; Animals ; *Drug Delivery Systems/methods ; *Nanoparticles/chemistry/administration & dosage ; Blood-Brain Barrier/metabolism ; Drug Carriers/chemistry ; },
abstract = {Brain disorders, encompassing neurodegenerative conditions and intracranial neoplasms, present formidable obstacles in the realm of pharmacological delivery due to the existence of athe blood-brain barrier (BBB) and the restricted bioavailability of therapeutic agents. Alginate-derived nanoformulations have emerged as highly promising systems for drug delivery, offering attributes such as biocompatibility, regulated release, and improved targeting efficacies. This review investigates contemporary advancements in alginate-based nanoformulations, with a particular emphasis on their efficacy in surmounting obstacles to successful pharmacological delivery to the brain. Initially, we furnish a comprehensive overview of alginate, underscoring its pertinent properties, biomedical applications, and inherent limitations. Subsequently, the discourse progresses to strategies for nanoformulation, which encompass lipid-based, polymeric, and inorganic methodologies, with a focus on their benefits in relation to cerebral targeting. Moreover, this review entails the therapeutic potential of alginate-based nanoformulations in addressing significant neurological disorders, including Alzheimer's disease, Parkinson's disease, brain tumours, traumatic brain injury, epilepsy, and amyotrophic lateral sclerosis. By amalgamating cutting-edge nanotechnology with the distinctive properties of alginate, these formulations signify a promising pathway for the advancement of efficacious therapies aimed at brain targeting. Additionally, prospective research trajectories and challenges associated with the optimization of alginate-based nanocarriers for clinical applications are also elucidated.},
}

*Alginates/chemistry/administration & dosage
Humans
*Brain Diseases/drug therapy
Animals
*Drug Delivery Systems/methods
*Nanoparticles/chemistry/administration & dosage
Blood-Brain Barrier/metabolism
Drug Carriers/chemistry

@article {pmid40517187,
year = {2026},
author = {Haro-Martínez, E and Muscolino, E and Moral, N and Duran, J and Fornaguera, C},
title = {Crossing the blood-brain barrier: nanoparticle-based strategies for neurodegenerative disease therapy.},
journal = {Drug delivery and translational research},
volume = {16},
number = {3},
pages = {797-824},
pmid = {40517187},
issn = {2190-3948},
support = {2021 SGR 00537//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; 2024-LLAV-00042//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; ICREA Acadèmia 2024//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; 202207-31//Fundació la Marató de TV3/ ; PID2020-118699GB-100//Agencia Estatal de Investigación/ ; Not specified//Fundación Ramón Areces/ ; FISDUR-2024//Departament d'Universitats, Recerca i Societat de la Informació/ ; },
mesh = {Humans ; *Blood-Brain Barrier/metabolism ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Nanoparticles/administration & dosage/chemistry ; Drug Delivery Systems ; Drug Carriers/chemistry ; },
abstract = {Neurodegenerative conditions, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease, represent a critical medical challenge due to their increasing prevalence, severe consequences, and absence of curative treatments. Beyond the need for a deeper understanding of the fundamental mechanisms underlying neurodegeneration, the development of effective treatments is hindered by the blood-brain barrier, which poses a major obstacle to delivering therapeutic agents to the central nervous system. This review provides a comprehensive analysis of the current landscape of nanoparticle-based strategies to overcome the blood-brain barrier and enhance drug delivery for the treatment of neurodegenerative diseases. The nanocarriers reviewed in this work encompass a diverse array of nanoparticles, including polymeric nanoparticles (e.g. micelles and dendrimers), inorganic nanoparticles (e.g. superparamagentic iron oxide nanoparticles, mesoporous silica nanoparticles, gold nanoparticles, selenium and cerium oxide nanoparticles), lipid nanoparticles (e.g. liposomes, solid lipid nanoparticles, nanoemulsions), as well as quantum dots, protein nanoparticles, and hybrid nanocarriers. By examining recent advancements and highlighting future research directions, we aim to shed light on the promising role of nanomedicine in addressing the unmet therapeutic needs of these diseases.},
}

Humans
*Blood-Brain Barrier/metabolism
*Neurodegenerative Diseases/drug therapy/metabolism
Animals
*Nanoparticles/administration & dosage/chemistry
Drug Delivery Systems
Drug Carriers/chemistry

@article {pmid40519824,
year = {2025},
author = {Michalec, B and Forbes, CE and Pardon, K and Ayala, B and Beltran, DG and Douille, C and Felix, K and Gnall, S and Hoenack, M and McKeever, B and Nguyen, D and Piemonte, N and Portle, S},
title = {A scoping review of emotional contagion research with human subjects: identifying common trends of previous research and potential areas for future research.},
journal = {Frontiers in psychology},
volume = {16},
number = {},
pages = {1573375},
pmid = {40519824},
issn = {1664-1078},
abstract = {INTRODUCTION: Emotional contagion (EC) involves the automatic mimicry and synchronization of expressions, vocalizations, and movements, resulting in emotional alignment between individuals. Despite consistent scholastic explorations of the various nuances and tenets associated with emotional contagion processes and outcomes, there has yet to be a thorough review of human subjects-based emotional contagion research.

METHODS: This review examines human subjects EC research trends, analyzing 277 articles (published from 1992 to 2022) to identify common conceptualizations, triggers, and measurement methods.

RESULTS: Analyses indicated that Hatfield et al.'s classic conceptualization is the most cited, and common triggers include facial expressions in images and videos, and real-time interactions - though many studies did not stimulate EC. While many studies did utilize validated EC scales, about 28% of the studies reviewed used non-validated questions to measure EC. Moreover, the EC research reviewed heavily relies on college-aged, predominantly white participants, indicating a need for more diverse samples.

DISCUSSION: Future EC research should explore processes and nuances associated with EC among older adults, minoritized groups, and diverse contexts (e.g., healthcare, schools), using novel triggers and multiple measurement methods.},
}

@article {pmid40523602,
year = {2025},
author = {Horikawa, I and Yamada, L and Harris, BT and Harris, CC},
title = {Δ133p53α-mediated inhibition of astrocyte senescence and neurotoxicity as a possible therapeutic approach for neurodegenerative diseases.},
journal = {Neuroscience},
volume = {580},
number = {},
pages = {54-61},
pmid = {40523602},
issn = {1873-7544},
support = {ZIA BC011496/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Astrocytes/metabolism/drug effects/pathology ; *Cellular Senescence/physiology ; *Tumor Suppressor Protein p53/metabolism ; *Neurodegenerative Diseases/metabolism/therapy ; Animals ; Protein Isoforms/metabolism ; },
abstract = {Non-neuronal glial cells in the brain, such as astrocytes, play essential roles in maintaining the functional integrity of neuronal cells. A growing body of evidence suggests that cellular senescence of astrocytes, characterized by loss of proliferative potential and secretion of neurotoxic cytokines, makes significant contribution to neurotoxicity in Alzheimer's disease and a wide range of other neurodegenerative diseases. This review discusses the beneficial effects of Δ133p53α, a natural p53 protein isoform that inhibits p53-mediated cellular senescence, thereby protecting astrocytes from senescence, highlights its potential as a therapeutic target, and underscores the need for continued research in this area. Both in senescent human astrocytes in culture, whether induced by replicative exhaustion, irradiation or exposure to amyloid-β, and in brain tissues with increased senescent astrocytes from patients with Alzheimer's disease, the expression levels of endogenous Δ133p53α protein were consistently and significantly reduced. The lentiviral vector-driven expression of Δ133p53α protected cultured human astrocytes from cellular senescence and neurotoxic secretory phenotype, leading to their cellular reprogramming to a neuroprotective state associated with neurotrophic growth factors. We thus propose that Δ133p53α is worth testing as a therapeutic target that can be enhanced in a wide range of neurodegenerative diseases with accumulated senescent astrocytes, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and chronic traumatic encephalopathy due to traumatic brain injury. We hypothesize that a Δ133p53α-mediated cellular reprogramming approach and a senolytic or senomorphic approach, both targeting non-neuronal cells, may be complementary with each other, and may cooperate with neuron-protecting or amyloid-β-targeting therapies currently in use.},
}

Humans
*Astrocytes/metabolism/drug effects/pathology
*Cellular Senescence/physiology
*Tumor Suppressor Protein p53/metabolism
*Neurodegenerative Diseases/metabolism/therapy
Animals
Protein Isoforms/metabolism

@article {pmid40524150,
year = {2025},
author = {Cozzi, M and Tedesco, B and Ferrari, V and Chierichetti, M and Pramaggiore, P and Cornaggia, L and Magdalena, R and Brodnanova, M and Mohamed, A and Milioto, C and Piccolella, M and Galbiati, M and Rusmini, P and Crippa, V and Gellera, C and Magri, S and Taroni, F and Cristofani, R and Poletti, A},
title = {One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {287},
pmid = {40524150},
issn = {1478-811X},
support = {PRIN- Progetti di ricerca di interesse nazionale - bando 2022, PNRR finanziato dall'Unione europea- Next Generation EU, componente M4C2, investimento 1.1 n. P20225R4Y5//Ministero dell'Università e della Ricerca/ ; PRIN-Progetti di ricerca di interesse nazionale n. 2022EFLFL8//Ministero dell'Università e della Ricerca/ ; 23236//AFM-Téléthon/ ; 739510//European Network for Rare Neurological Disorders/ ; piano di sviluppo della ricerca (PSR) UNIMI//Università degli Studi di Milano/ ; R21 AR080407/AR/NIAMS NIH HHS/United States ; Travelling Fellowship n. JCSTF2205742//Company of Biologists/ ; R21AR080407/AR/NIAMS NIH HHS/United States ; RF-2018-12367768//Ministero della Salute/ ; . 2021-1544//Fondazione Cariplo/ ; Scientific Exchange Grant n. 9643//European Molecular Biology Organization/ ; 2025 grant//CureHSPB8,USA/ ; PRIN-Progetti di ricerca di interesse nazionale n. 2020PBS5MJ//Ministero dell'Università e della Ricerca/ ; CP 20/2018 (Care4NeuroRare)//Fondazione Regionale per la Ricerca Biomedica/ ; 2020 grant//Kennedy's Disease Association/ ; 2018 grant//Kennedy's Disease Association/ ; },
mesh = {Humans ; *Kinesins/genetics/chemistry/metabolism ; Phenotype ; Animals ; *Neurodevelopmental Disorders/genetics ; *Neurodegenerative Diseases/genetics ; Mutation ; },
abstract = {Kinesin family member 5 A (KIF5A) is a neuron-specific molecular motor involved in anterograde transport. KIF5A mediates a wide range of trafficking processes that are only partially shared with the other members of the KIF5 family. Since 2002, several disease-causing mutations have been found in the KIF5A gene and a link between the specific domain in the encoded protein affected by mutations and the associated phenotype has become evident. Point mutations targeting KIF5A motor and stalk domains, that are expected to impair KIF5A motility, mainly associate with spastic paraplegia type 10 (SPG10) and axonal Charcot-Marie-Tooth (CMT) disease. Oppositely, translational frameshifts causing the elongation of KIF5A tail enhance KIF5A migration towards cell periphery, induce kinesin aggregation, and are linked to amyotrophic lateral sclerosis (ALS) or neonatal intractable myoclonus (NEIMY). This review correlates KIF5A structure and roles in neuronal trafficking with its involvement in the above-mentioned neurodegenerative and neurodevelopmental conditions.},
}

Humans
*Kinesins/genetics/chemistry/metabolism
Phenotype
Animals
*Neurodevelopmental Disorders/genetics
*Neurodegenerative Diseases/genetics
Mutation

@article {pmid40525139,
year = {2025},
author = {Abou Izzeddine, N and Ahmad, K and Bacha, C and Jabbour, M and Najjar, M and Salhab, S and Ghadieh, HE and Kanaan, A and Azar, S and Khattar, ZA and Harb, F},
title = {The microbial guardians: Unveiling the role of gut microbiota in shaping neurodegenerative disease.},
journal = {IBRO neuroscience reports},
volume = {19},
number = {},
pages = {17-37},
pmid = {40525139},
issn = {2667-2421},
abstract = {The gut microbiota, a complex community of microorganisms residing in the digestive tract, plays a pivotal role in human health. Recent studies have highlighted its significant impact on neurodegenerative diseases, conditions that pose profound challenges to affected individuals and society at large. This review explores the intricate relationship between gut microbiota and the progression of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. We delve into the dynamic ecosystem of gut microbiota, examining factors influencing its composition and the bidirectional communication established via the gut-brain axis. Emerging evidence suggests that gut microbiota can modulate neurodegenerative disease progression through mechanisms including inflammatory responses, production of neuroactive substances, and regulation of neurotransmitters. Furthermore, we discuss the potential therapeutic implications of targeting gut microbiota with probiotics, prebiotics, and postbiotics. While promising, these interventions face challenges and limitations that must be addressed through ongoing research. Understanding the role of gut microbiota in neurodegenerative diseases is crucial for developing innovative therapeutic strategies and improving patient outcomes.},
}

@article {pmid40527647,
year = {2025},
author = {Thijs, Z and Calzada, A and Sosa, M and Dumican, M},
title = {The Association Between Bilingualism and Voice Quality in Spanish-English Bilingual Speakers: A Systematic Review.},
journal = {Journal of voice : official journal of the Voice Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jvoice.2025.05.027},
pmid = {40527647},
issn = {1873-4588},
abstract = {OBJECTIVE/HYPOTHESIS: The vast majority of the global population speaks more than one language. In the United States, Spanish-English bilingual speakers are the largest bilingual group. Yet, the potential effect of being bilingual, specifically a Spanish-English speaker, on voice quality is poorly understood. The current study consequently set out to systematically review the literature on the association between being a Spanish-English bilingual speaker and voice quality.

STUDY DESIGN: Systematic review.

METHODS: A systematic review of association was conducted using Moola et al's guidelines. A search string was developed and run in May 2024 across three databases: MEDLINE (via PubMed), CINAHL via EBSCOhost, and Scopus. After duplicate removal, title, and abstract screening, full-text screening was performed, and peer-reviewed articles considering voice quality measures in Spanish-English bilingual speakers were included. Data were extracted and presented in table format, and the quality of the articles was assessed using the Checklist for Analytical Cross-Sectional Studies.

RESULTS: In total, 685 records were retrieved, with 485 remaining after duplicate removal. After title and abstract screening, 25 full texts were screened, including 8 articles in the review. Five studies included acoustic measures describing voice quality, with only three including auditory-perceptual analysis. The most commonly considered vocal trait in Spanish-English bilinguals was vocal fry, with the included studies pointing to increased vocal fry use when speaking English.

CONCLUSIONS: Only a few articles discuss potential vocal changes in Spanish-English bilinguals. Further research is needed to elucidate any potential vocal changes related to being a bilingual speaker, as the current small number of studies and mixed findings make drawing conclusions difficult. More standardization across voice and language assessment could be beneficial.},
}

@article {pmid40528459,
year = {2025},
author = {Yang, M and Zhang, A and Chen, M and Cao, J},
title = {Advances in Circulating Biomarkers for Neurodegenerative Diseases, Traumatic Brain Injuries, and Central Nervous System Tumors.},
journal = {Annals of laboratory medicine},
volume = {45},
number = {4},
pages = {381-390},
pmid = {40528459},
issn = {2234-3814},
mesh = {Humans ; *Brain Injuries, Traumatic/diagnosis/blood ; *Neurodegenerative Diseases/diagnosis/blood ; *Biomarkers/blood/cerebrospinal fluid ; *Central Nervous System Neoplasms/diagnosis/blood ; Enzyme-Linked Immunosorbent Assay ; tau Proteins/blood/cerebrospinal fluid ; },
abstract = {Neurological disorders, including neurodegenerative diseases, traumatic brain injuries (TBI), and central nervous system (CNS) tumors, are complex conditions that significantly impact patients globally. Timely diagnosis and monitoring are critical for improving outcomes, driving the need for reliable biomarkers. Specifically, biomarkers detectable in cerebrospinal fluid (CSF) and blood offer important insights into disease presence and progression. This review explores the evolution of circulating blood biomarkers for neurodegenerative diseases, TBI, and CNS tumors, highlighting advanced detection technologies from enzyme-linked immunosorbent assays (ELISAs) to electrochemiluminescence (ECL) assays, single-molecule arrays (Simoa), and mass spectrometry. Advanced technologies with enhanced sensitivity and specificity, particularly in detecting low-abundance analytes, facilitate the investigation of CSF biomarkers for various neurological disorders. We also describe the progress in blood-based biomarkers for , emerging as less invasive alternatives to CSF sampling. Clinically, the implementation of Alzheimer's disease (AD) blood biomarkers Aβ42/Aβ40 ratio and Apolipoprotein E isoform-specific peptide can aid the diagnosis, while p-tau181 and p-tau217 differentiates AD dementia from non-AD neurodegenerative diseases. Blood glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 are used in ruling out mild TBI. Despite these innovations, challenges remain, including assay standardization, sensitivity/specificity trade-offs, and the requirement for longitudinal studies to understand biomarker utility over time. Future research should focus on addressing these challenges to fully realize the potential of blood-based biomarkers in neurological disorder diagnostics and patient care.},
}

Humans
*Brain Injuries, Traumatic/diagnosis/blood
*Neurodegenerative Diseases/diagnosis/blood
*Biomarkers/blood/cerebrospinal fluid
*Central Nervous System Neoplasms/diagnosis/blood
Enzyme-Linked Immunosorbent Assay
tau Proteins/blood/cerebrospinal fluid

@article {pmid40533880,
year = {2025},
author = {Liu, W and Wang, S and Zhang, T and Zhu, H and Chang, N and Zhang, L and Hu, Z},
title = {A Review of Preparation of Low-Carbon Cementitious Materials from Chemically Activated Red Mud: Synergy, Hydration Mechanism, Rheological Properties and Applications.},
journal = {Langmuir : the ACS journal of surfaces and colloids},
volume = {41},
number = {25},
pages = {15735-15751},
doi = {10.1021/acs.langmuir.5c01088},
pmid = {40533880},
issn = {1520-5827},
abstract = {Red mud, a byproduct of the alumina refining process, is generated at a rate of 1-2.5 tonnes per tonne of alumina produced. In 2022, China's alumina production totaled 77.475 million tonnes, contributing over 4 billion tonnes of accumulated red mud, which is the third-largest industrial solid waste in the country. Red mud's high alkalinity and presence of toxic elements pose environmental challenges, particularly in terms of disposal. This review provides a comprehensive examination of red mud-based cementitious materials, focusing on their preparation, properties, and environmental impact. By combining red mud with high-calcium and silica-aluminum solid wastes and enhancing its reactivity through mechanical grinding or thermal activation, red mud's cementitious activity can be significantly improved. Optimized compositions, with a Ca/Si ratio of 2.05 and Al/S ratio of 0.70, have achieved compressive strengths of up to 63.9 MPa at 28 day. Durability studies highlight the material's resistance to chloride ion penetration and sulfate attack, with reduced permeability enhancing long-term performance. Additionally, environmental assessments confirm that stabilization and solidification techniques effectively mitigate heavy metal leaching, ensuring compliance with EPA standards. Despite these advancements, challenges remain in optimizing red mud activation processes, improving rheological properties, and reducing production costs. Future research should focus on refining activation methods, enhancing hydration mechanisms, and developing scalable industrial applications. By addressing these gaps, red mud-based cementitious materials can become a sustainable solution for eco-friendly construction, supporting global efforts to repurpose industrial byproducts into low-carbon, durable building materials.},
}