@article {pmid41772227,
year = {2026},
author = {Rizzo, GEM and Vanella, G and Fuccio, L and Facciorusso, A and Mazza, S and Catena, F and Fabbri, C and Anderloni, A and Tarantino, I},
title = {Endoscopic ultrasound-guided gastrointestinal anastomoses for the treatment of afferent limb syndrome: a systematic review and meta-analysis.},
journal = {Surgical endoscopy},
volume = {40},
number = {5},
pages = {3944-3955},
pmid = {41772227},
issn = {1432-2218},
mesh = {Humans ; *Afferent Loop Syndrome/surgery ; *Endosonography/methods ; Anastomosis, Surgical/methods ; *Ultrasonography, Interventional/methods ; *Jejunostomy/methods ; *Gastric Bypass/methods/adverse effects ; },
abstract = {BACKGROUND AND STUDY AIMS: Afferent limb syndrome (ALS) is a rare condition resulting in a mechanical obstruction in the afferent loop after surgical gastrointestinal (GI) reconstruction. Endoscopic ultrasound (EUS)-guided gastrojejunostomy (GJ) or jejunojejunostomy (JJ) is increasing in clinical practice. Therefore, the aim of this systematic review with meta-analysis is to evaluate the efficacy and safety of EUS-GJ or EUS-JJ for ALS.

PATIENTS AND METHODS: The most important medical databases were systematically searched through May 2025. The primary outcome was technical success of EUS-GJ/JJ for ALS. Secondary outcomes were clinical success, safety, and recurrence rate. A random-effects model was used to pool the results. Heterogeneity was expressed as inconsistency index (I[2]) and explored through subgroup analyses.

RESULTS: 9 studies (all retrospective) involving 188 patients were included in the analysis. The weighted mean age was 65.38(± 10.57) years and the etiology of the ALS was mostly malignant. Technical success was 96.3% (CI95% 93.2-99.4%, I[2] = 0%). Clinical success was 95% (CI95% 91.2-98.7%, I[2] = 0%) and adverse events (AEs) rate was 6.9% (CI95% 2.9-11.1%, I[2] = 0%). Recurrence rate was 16.6% (CI95% 7.7-25.4%, I[2] = 43.79%). Subgroup analyses showed differences in the recurrence rate between the use of a fully covered self-expandable metal stent (FCSEMS) (35.9% [CI95% 20.3-51.6%, I[2] = 0%]) and a lumen-apposing metal stent (LAMS)(10.4% [CI95% 4-16.8%, I[2] = 0%], p = 0.003). Follow-up ranged from a median of 96.5 to 185 days.

CONCLUSIONS: EUS-guided GI anastomosis is an effective treatment for ALS, showing high technical and clinical success rates and a low incidence of AEs. The use of LAMS over FCSEMS seems to reduce the recurrence rate, suggesting the routine use of LAMS in the case of EUS-guided GI anastomosis for treating ALS.},
}

Humans
*Afferent Loop Syndrome/surgery
*Endosonography/methods
Anastomosis, Surgical/methods
*Ultrasonography, Interventional/methods
*Jejunostomy/methods
*Gastric Bypass/methods/adverse effects

@article {pmid42374626,
year = {2026},
author = {Walton, EI and Sun, J},
title = {Microbiome and metabolites impact enteric and central nervous systems in ALS.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2692737},
doi = {10.1080/19490976.2026.2692737},
pmid = {42374626},
issn = {1949-0984},
mesh = {*Amyotrophic Lateral Sclerosis/microbiology/metabolism/physiopathology ; Humans ; *Central Nervous System/metabolism/microbiology/physiopathology ; *Enteric Nervous System/metabolism/physiopathology/microbiology ; *Gastrointestinal Microbiome/physiology ; Animals ; Dysbiosis/microbiology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) has been linked to gastrointestinal symptoms and alterations in the gut microbiota. The enteric nervous system (ENS) coordinates intestinal function and sits at the host-microbe interface. The mechanisms by which luminal changes relay to the central nervous system (CNS), where motor neurons reside, have yet to be completely defined. In this narrative review, we first present evidence from ALS patient cohorts and preclinical models alongside mechanistic studies of infection, dysbiosis, and related neurodegenerative diseases to discuss how the microbiota and its metabolites may affect the ENS and CNS in ALS. Next, we propose a plausible mechanism of ALS pathogenesis through the gut-microbiome-brain axis. We further offer a summary of clinical trials that have studied the impacts of the microbiota on human ALS. Finally, we discuss future directions for studies of microbiota-ENS-CNS interactions in ALS. Better understanding of the dynamic interactions among the microbiota, microbial metabolites, neuroactive metabolites, and inflammation through the ENS/CNS in ALS will provide innovative insights into ALS prevention and treatment.},
}

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

@article {pmid42368190,
year = {2026},
author = {Meng, J and Deng, ZJ and Zhang, J and Yu, W and Wu, X and Lei, P},
title = {Atypical involvement of Alzheimer's tau proteins in diseases beyond tauopathies.},
journal = {Life medicine},
volume = {5},
number = {3},
pages = {lnag016},
pmid = {42368190},
issn = {2755-1733},
abstract = {Tau is a microtubule-associated protein traditionally involved in a collective group of disorders termed "tauopathy", including Alzheimer's disease. Tau protein self-aggregates and forms neurofibrillary tangles in neurons, which are considered a pathological hallmark of tauopathies. While the roles of neuronal tau in tauopathies have been extensively investigated, recent studies have shed light on its roles in other diseases without tau pathology and in other cells. In this review, we aim to discuss the "atypical" pathological involvement of tau in diseases other than tauopathies, including brain diseases (e.g., amyotrophic lateral sclerosis, multiple sclerosis, and spinal cord injury), vascular diseases (stroke and hypertension), diabetes, and cancers. We have discussed the expression and functions of tau in cell types other than neurons, and have summarized the evidence supporting a role of tau in these diseases. These cross-disease studies collectively suggest that tau protein is more broadly implicated in mechanisms such as axonal instability, dysregulated cell signaling, inflammatory activation, and cell death, independent of its aggregation, contributing to our knowledge of the functions of tau and the myriad ways in which it may be involved in pathological processes.},
}

@article {pmid42369228,
year = {2026},
author = {Wojtowicz, E and Yous, ML and Baxter, P and Kaasalainen, S},
title = {Talking about the hypothetical future: Serious illness communication for residents living with dementia in long-term care homes - An integrative review.},
journal = {Palliative care and social practice},
volume = {20},
number = {},
pages = {26323524261462628},
pmid = {42369228},
issn = {2632-3524},
abstract = {BACKGROUND: In long-term care (LTC) homes, residents living with dementia frequently experience serious illness communication that is crisis-initiated and oriented to institutional documentation (e.g., transfer and resuscitation orders), rather than iterative, values-based discussions aligned with a palliative approach and substitute decision-making frameworks. Unpaid care partners often make high-stakes decisions with limited preparation, and residents are inconsistently included.

OBJECTIVES: To explore how serious illness communication occurs with residents living with dementia, unpaid care partners, and healthcare providers in LTC, and to identify practice-relevant communication strategies and contextual factors applicable to clinical practice.

METHODS: An integrative review following Toronto and Remington's six-stage methodology included 31 high-relevance studies (qualitative, quantitative, mixed methods, reviews, theoretical) published from 2015 to 2025 on serious illness, goals-of-care, or end-of-life communication in LTC dementia care. Directed content analysis was guided by Tarbi et al.'s basic science of communication in serious illness (lexical, non-lexical, contextual elements, and outcomes).

RESULTS: Serious illness communication was predominantly biomedical and documentation-focused, often occurring at admission or during crises and directed mainly to unpaid care partners, with limited resident involvement. Lexical practices such as clear, jargon-free information, explicit invitations to discuss "what matters most," and early conversations about hypothetical future scenarios enhanced trust, preparedness, and alignment of care with resident values. Non-lexical elements (tone, eye contact, pacing, use of silence) shaped perceived empathy but were seldom explicitly addressed by interventions.

CONCLUSIONS: For LTC healthcare providers, embedding earlier, iterative serious illness communication, explicitly involving residents where possible, and cultivating both lexical and non-lexical skills are key to achieving relationship-centred, legally compliant, and goal-concordant palliative approaches to care.​.},
}

@article {pmid42369360,
year = {2026},
author = {Keihani, A and Hassani, M and Sajadi, SS and Modarresi, SA and Khoshkholgh, M and Haresabadi, M and Amani, K and Jourahmad, Z and Ferrarelli, F},
title = {Assessing upper motor neuron dysfunction in ALS: from TMS-EEG and EMG neurophysiology to a combined tFUS-TMS translational framework.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1798525},
pmid = {42369360},
issn = {1664-2295},
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of upper motor neurons (UMNs) and lower motor neurons (LMNs). Despite significant advances in molecular and neuroimaging biomarkers, the initial site of pathology and the causal contribution of UMN dysfunction to disease progression remain undetermined. Accumulating neurophysiological evidence points to cortical hyperexcitability as an early and potentially upstream mechanism, raising the possibility that UMN pathology drives LMN degeneration through an anterograde dying-forward process. In this review, we synthesize findings from noninvasive brain stimulation (NIBS) studies, with particular emphasis on transcranial magnetic stimulation (TMS)-based neurophysiological markers of UMN dysfunction. We review evidence from TMS-electromyography (TMS-EMG) and TMS-electroencephalography (TMS-EEG) paradigms demonstrating cortical disinhibition and excitatory-inhibitory imbalance in ALS, consistent with impaired GABAergic interneuronal dysfunction and supportive of a cortical onset hypothesis. Finally, we propose integrating transcranial focused ultrasound (tFUS) with TMS as a novel experimental and translational framework to directly examine and modulate cortical hyperexcitability and test the causal role of UMN dysfunction in ALS. The combination of targeted neuromodulation with sensitive neurophysiological readouts in controlled experimental designs offers a promising avenue to advance mechanistic insight, refine biomarkers, and inform mechanism-based therapeutic strategies. Together, these approaches position noninvasive neurophysiology as a powerful tool for elucidating UMN dysfunction in ALS.},
}

@article {pmid42370313,
year = {2026},
author = {Alkorom, S and Chong, MC and Che Seman, NH and Aqtam, I},
title = {Resilience-Building Interventions and Advanced Life Support Competency for Emergency Nurses in Palestinian Hospitals: A Scoping Review.},
journal = {SAGE open nursing},
volume = {12},
number = {},
pages = {23779608261464872},
pmid = {42370313},
issn = {2377-9608},
abstract = {BACKGROUND: Emergency nurses in Palestinian hospitals operate under chronic stress related to political instability, resource constraints, and high trauma exposure. These conditions may affect both psychological resilience and Advanced Life Support (ALS) competency, yet the evidence base remains unclear. This scoping review sought to map the available body of literature about psychological resilience and ALS competency among emergency nurses in Palestine, identify gaps in research, and determine the relationship between psychological resilience and ALS competency, which is the core focus of this review.

METHODS: Following PRISMA-ScR guidelines and JBI scoping review methodology, a comprehensive search of seven electronic databases and grey literature was conducted for studies published between January 2000 and January 2026. Two reviewers independently screened studies and extracted data using a standardized, pilot-tested charting form. Findings were synthesized descriptively using narrative synthesis organized around the review objectives.

RESULTS: From 1,292 records identified, 18 studies met inclusion criteria. Most studies were descriptive or correlational (94.4%). Burnout prevalence among emergency nurses ranged from 64% to 72.9%, and substantial gaps in ALS/BLS knowledge were reported, including low accuracy in resuscitation sequence identification (26.6%). Only one intervention study was identified, evaluating simulation-based BLS training. No studies were found that assessed resilience-based or comprehensive programs which address psychological wellbeing and clinical competency issues. There were no studies that specifically analyzed the connection between psychological resilience and competency in ALS.

CONCLUSION: The existing literature on Palestinian emergency nurses is dominated by descriptive studies, with a marked absence of intervention research. Despite documented psychological distress and clinical competency gaps, no studies have evaluated psychological resilience-focused or integrated interventions. This review highlights critical evidence gaps and provides a foundation for future intervention-oriented research.},
}

@article {pmid42371053,
year = {2026},
author = {Stipa, G and Colosimo, C and Vanacore, N},
title = {Neurodegenerative diseases and environmental risk factors: an overview of the available scientific evidence.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42371053},
issn = {1435-1463},
abstract = {Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are among the most well-known and prevalent neurodegenerative disorders. These diseases result from an interaction between the environment and genetically predisposed individuals. This review examines the evidence available in the literature underlying this multifaceted interaction, focusing on various chemical substances such as metals, fertilizers, and herbicides, as well as toxic agents of microbiological origin, including cyanobacteria and their neurotoxins. In addition, the pathways through which toxic substances can enter the human body are discussed, such as air and water, which may lead to absorption through the lungs, the gastrointestinal tract, the skin, and mucosae. The routes by which neurotoxic substances gain access to the human body may help explain the increased risk of developing neurodegenerative diseases observed in sports played on soil and grass surfaces, such as soccer, American football, and golf.},
}

@article {pmid42373582,
year = {2026},
author = {Granger, SM and Staniforth, RA and Snorradottir, AO and Cooper-Knock, J and De Vos, KJ and Highley, JR},
title = {Unravelling the Significance of Cystatin C and Bunina Bodies in Amyotrophic Lateral Sclerosis Pathogenesis.},
journal = {Neuropathology and applied neurobiology},
volume = {52},
number = {4},
pages = {e70083},
doi = {10.1111/nan.70083},
pmid = {42373582},
issn = {1365-2990},
support = {/MNDA_/Motor Neurone Disease Association/United Kingdom ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Cystatin C/metabolism ; Animals ; *Inclusion Bodies/pathology/metabolism ; *Motor Neurons/pathology/metabolism ; DNA-Binding Proteins/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a fatal neurodegenerative disease primarily affecting motor neurons. Two key protein inclusions found in lower motor neurons serve as neuropathological hallmarks of the disease in human tissue: the TDP43-positive inclusion and the cystatin C-positive Bunina body. Despite their diagnostic specificity and presence in most sporadic and familial ALS cases, Bunina bodies remain poorly understood, and their true prevalence is likely underestimated. The co-occurrence of the Bunina body and the TDP43 inclusion may provide valuable insights into the development of TDP43 pathology in ALS. Thorough characterisation of the Bunina body is needed to understand this interplay and the broader pathomechanisms of disease. This review examines our current knowledge of Bunina bodies and the biochemical properties of cystatin C that may promote its aggregation. Sequestration and aggregation of cystatin C into Bunina bodies may diminish its neuroprotective functions, including cysteine protease inhibition, autophagy induction and anti-amyloidogenic activity, thereby contributing to ALS pathogenesis. This review also evaluates findings from human post-mortem tissue and ALS disease models, discussing the value and limitations of these models in the context of Bunina bodies and TDP43 pathology. Finally, we discuss cystatin C's use as a biomarker and its therapeutic potential. A deeper understanding of cystatin C biology, its relationship with TDP43 pathology and improved ALS models will be essential for determining whether targeting cystatin C could provide a viable avenue for future ALS therapies.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/metabolism
*Cystatin C/metabolism
Animals
*Inclusion Bodies/pathology/metabolism
*Motor Neurons/pathology/metabolism
DNA-Binding Proteins/metabolism

@article {pmid42373784,
year = {2026},
author = {Li, Y and Ulrich, JD and Holtzman, DM},
title = {Adaptive immunity in the pathogenesis of neurodegeneration.},
journal = {Nature immunology},
volume = {27},
number = {7},
pages = {1375-1389},
pmid = {42373784},
issn = {1529-2916},
support = {AG085374//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AG069701//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AG078106//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; AG083977//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; NS090934//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
mesh = {Humans ; *Adaptive Immunity/immunology ; *Neurodegenerative Diseases/immunology/pathology/therapy ; Animals ; Microglia/immunology ; *Central Nervous System/immunology/pathology ; Astrocytes/immunology ; Immunity, Innate ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and others, are a group of neurological disorders characterized by progressive neuronal loss in the central nervous system (CNS) and the deterioration of CNS function. Multiple lines of evidence have highlighted activation of innate immune cells in the CNS, namely microglia and astrocytes, as hallmark pathological features in neurodegeneration and key drivers of disease progression. Advances in genetic, neuropathological and experimental studies also underscore the potential role of the adaptive immune system in disease pathogenesis. Here we summarize the current understanding of how adaptive immunity can shape the progression of neurodegenerative diseases and highlight cross-disease parallels and potentially shared mechanisms. We also examine cellular events leading to the recruitment of peripheral immune cells to the CNS, as well as candidate antigens driving the adaptive immune response. Last, we discuss potential therapeutic strategies to treat neurodegeneration via the manipulation of adaptive immune cells.},
}

Humans
*Adaptive Immunity/immunology
*Neurodegenerative Diseases/immunology/pathology/therapy
Animals
Microglia/immunology
*Central Nervous System/immunology/pathology
Astrocytes/immunology
Immunity, Innate

@article {pmid42373786,
year = {2026},
author = {Guo, AX and Fisher, TM and Comandante-Lou, N and De Jager, PL and Liddelow, SA},
title = {Innate immune signaling and functions in astrocytes.},
journal = {Nature immunology},
volume = {27},
number = {7},
pages = {1364-1374},
pmid = {42373786},
issn = {1529-2916},
support = {AARF-24-1313800/ALZ/Alzheimer's Association/United States ; U01 AG061356/AG/NIA NIH HHS/United States ; },
mesh = {*Astrocytes/immunology/metabolism ; Humans ; *Immunity, Innate/immunology ; Animals ; *Signal Transduction/immunology ; Toll-Like Receptors/metabolism/immunology ; Innate Immunity Recognition ; Inflammasomes/metabolism/immunology ; },
abstract = {Astrocytes, long considered supportive cells of the central nervous system (CNS), have critical roles in innate immunity. This Review explores immune signaling pathways in astrocytes, including pattern recognition through Toll-like receptors, nucleic acid sensors and inflammasomes. These pathways enable the detection of danger signals and initiate protective responses and endogenous innate immune functions. Downstream signaling pathways, including the interferon, NF-κB and STAT3 pathways, mediate astrocyte reactivity and drive cytokine secretion, antiviral responses, phagocytosis and many other immune functions. While these responses are crucial for CNS health, their dysregulation can contribute to chronic inflammation and neurodegeneration in conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. Additionally, astrocytes exhibit regional heterogeneity in their immune behaviors, which may influence disease trajectories. We highlight unresolved questions regarding the immune functions of astrocytes, their interplay with professional immune cells and their dual protective and pathological roles.},
}

*Astrocytes/immunology/metabolism
Humans
*Immunity, Innate/immunology
Animals
*Signal Transduction/immunology
Toll-Like Receptors/metabolism/immunology
Innate Immunity Recognition
Inflammasomes/metabolism/immunology

@article {pmid41639347,
year = {2026},
author = {Tosi, M and Favero, F and Zuccalà, M and Visha, E and Caushi, F and Barizzone, N and Pomella, N and Follia, L and Corrado, L and Corà, D and Martignetti, L and Leone, M and D'Alfonso, S},
title = {A multi-omics study on monozygotic twins discordant for amyotrophic lateral sclerosis and literature review underline a potential role for innate immunity and epigenetic dysregulation in disease mechanisms.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {3},
pages = {230},
pmid = {41639347},
issn = {1590-3478},
support = {DIG-ALS//AriSLA/ ; PRIN project GENIALS//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/immunology ; *Twins, Monozygotic/genetics ; Multiomics ; *Epigenesis, Genetic ; *Immunity, Innate/genetics ; Female ; Male ; DNA Methylation ; Middle Aged ; Aged ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration. Although genetic contributions to both familial and sporadic ALS (sALS) cases are well established, a substantial portion of ALS heritability remains unexplained, suggesting the involvement of other genetic and epigenetic factors. METHODS: To address this gap, we have devised a comprehensive multi-omics approach in a pair of Italian monozygotic twins discordant for ALS, performing DNA methylation, transcriptomic, and whole exome sequencing (WES). We then conducted a structured literature research on ALS-discordant monozygotic twins (n = 45) and on case-control sALS (~ 7000 patients and ~ 3000 controls), investigated for at least one of the omics approaches. RESULTS: Our exploratory analysis reveals distinct transcriptomic and epigenetic profiles underlying the discordant disease phenotypes in genetically identical individuals, particularly implicating immune system functions and brain development pathways. Notably, a comprehensive comparison of our results with existing literature underlined the involvement of pathways related to NK cell activation, chemokine production, and signal transduction, suggesting potential shared disease associated mechanisms across ALS cases. CONCLUSIONS: This hypothesis-generating study, although limited by the sample size, demonstrates the utility of multi-omics approaches in uncovering broader pathological insights into ALS, speculating on the possible contribution of innate immunity and epigenetic dysregulation in disease processes. This work provides a foundation for future research aimed at identifying disease-associated processes and biomarkers.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/immunology
*Twins, Monozygotic/genetics
Multiomics
*Epigenesis, Genetic
*Immunity, Innate/genetics
Female
Male
DNA Methylation
Middle Aged
Aged

@article {pmid41760955,
year = {2026},
author = {D'Amico, A and Cucunato, R and Schirò, G and Salemi, G and Ragonese, P and La Bella, V and Aridon, P and D'Amelio, M},
title = {KIF5A and ALS: a clinical and genetic description of a case series and review of literature.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {3},
pages = {},
pmid = {41760955},
issn = {1590-3478},
mesh = {Humans ; *Kinesins/genetics ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology ; Female ; Male ; Middle Aged ; Aged ; Adult ; Mutation ; Disease Progression ; },
abstract = {Approximately 10% of ALS (amyotrophic lateral sclerosis) cases show a family history, and the remaining 90% are sporadic. In 2018, through genome sequencing using two independent approaches, KIF5A was described as a novel ALS-associated gene. To describe clinical and genetic characteristics of a series of patients with motor neuron disease (MND), diagnosed at University Hospital of Palermo, carrying KIF5A variants. During 2019–2023, two hundred twenty-four patients with MND and healthy subjects with familial history of MND, underwent next-generation sequencing (NGS) for molecular analysis, including genetic testing for C9orf72 hexanucleotide-repeat expansion. The most mutated ALS genes, including KIF5A, were included in a NGS panel. Of the entire tested population, eight patients (including a brother and a sister) were found to carry KIF5A variants. Four patients had familial ALS, the other four were sporadic. Six patients were females (75%). Mean age at ALS onset was 59 years (33–75). Patients were evaluated according to the ALSFRS-revisited during follow-up visits. According to disease progression rate, five patients were defined as ∆FS ≤ 0.5 (slow-progressors), the remaining three patients showed a ∆FS > 1 (fast-progressors). Of the seven KIF5A variants, three are not already described in literature (respectively c.170 C > T, p.Thr57Met; c.2920T > G, p.Ser974Ala and c.2732 A > C, p.Lys911Thr). Two patients showed the association of variations in KIF5A with variations or mutations in other ALS genes, one of them carried a pathogenic variant of FUS (P525L). This study demonstrates phenotypic variability related to mutations in different regions of the same gene resulting in a susceptibility for the disease spectrum with different characteristics.},
}

Humans
*Kinesins/genetics
*Amyotrophic Lateral Sclerosis/genetics/physiopathology
Female
Male
Middle Aged
Aged
Adult
Mutation
Disease Progression

@article {pmid42345595,
year = {2026},
author = {de Sousa, SF and Marques, MDCMP and da Silva Amaral, GMM},
title = {Factors Influencing the Maintenance of Advanced Life Support Competencies Among Critical Care Professionals: A Scoping Review.},
journal = {Nursing in critical care},
volume = {31},
number = {4},
pages = {e70545},
pmid = {42345595},
issn = {1478-5153},
support = {UID/06291/2025//Fundação para a Ciência e a Tecnologia/ ; },
mesh = {Humans ; *Clinical Competence/standards ; *Critical Care/standards ; *Advanced Cardiac Life Support/standards ; },
abstract = {BACKGROUND: Advanced life support (ALS) competence may deteriorate within months after certification, but what supports ongoing competence in critical care remains unclear.

AIM: To map factors influencing maintenance of ALS competence among critical care professionals working in critical care settings.

STUDY DESIGN: Scoping review conducted in accordance with Joanna Briggs Institute guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. MEDLINE, CINAHL and the Cochrane Library were searched (from February to March 2025). We included peer-reviewed and grey sources from hospital-based critical care settings that assessed ALS competencies over time. Data were synthesised using inductive thematic analysis.

RESULTS: Twenty-five sources were included (19 peer-reviewed, 6 grey). Factors were mapped to three domains. Educational factors were most frequently reported and centred on simulation-based rehearsal, structured feedback and debriefing and spaced refreshers delivered in brief, frequent sessions. Institutional determinants related to protected training time, access to resources, standardised roles and content and monitoring through audit and feedback. Individual determinants included clinical exposure and experience, perceived preparedness and self-confidence, stress and cognitive load, engagement in ongoing learning and non-technical behaviours. Outcomes were largely simulation-based or self-reported, and longer-term durability was inconsistently assessed.

CONCLUSIONS: Maintenance of ALS competence appears to require coordinated educational and organisational supports; longitudinal evaluations with explicit definitions and validated outcomes are needed.

Critical care services may strengthen ALS competence maintenance by embedding recurrent, context-aligned rehearsal with feedback, supported by protected training time, accessible training infrastructure and ongoing performance monitoring.

REVIEW REGISTRATION: The review protocol was prospectively registered on the Open Science Framework https://doi.org/10.17605/OSF.IO/PEQJH.},
}

Humans
*Clinical Competence/standards
*Critical Care/standards
*Advanced Cardiac Life Support/standards

@article {pmid42347120,
year = {2026},
author = {Alves Ferreira, JM and Tukaiev, S and Giannouli, V},
title = {RNA-Binding Proteins in Ageing and Age-Related Disease.},
journal = {Neurology international},
volume = {18},
number = {6},
pages = {},
doi = {10.3390/neurolint18060112},
pmid = {42347120},
issn = {2035-8385},
abstract = {RNA-binding proteins (RBPs) are essential regulators of all aspects of RNA metabolism, including splicing, stability, localisation, translation, and degradation. Through their ability to recognise specific cis-elements in target transcripts, often via RNA-recognition motifs or other conserved domains, RBPs enable rapid cellular adaptation to stress and maintain proteostasis, particularly in post-mitotic tissues with limited transcriptional flexibility. Accumulating evidence positions RBPs as both modulators and drivers of the molecular hallmarks of ageing, including genomic instability, loss of proteostasis, mitochondrial dysfunction, cellular senescence, and chronic inflammation. This review synthesises peer-reviewed studies on the multifaceted roles of RNA-binding proteins in organismal ageing and age-related diseases. Key themes include the tissue- and age-dependent changes in expression of turnover and translation regulatory RBPs such as HuR (ELAVL1), AUF1 (HNRNPD), TIA-1, and tristetraprolin (ZFP36), which alter the stability of mRNAs encoding cell-cycle regulators, pro-inflammatory cytokines, and stress-response proteins. Systematic downregulation of core splicing factors, including PTBP1 and several heterogeneous nuclear ribonucleoproteins, drives widespread senescence-associated splicing alterations in pathways governing cell division, autophagy, DNA repair, and mitochondrial function, suggesting a causal contribution to the senescent phenotype. Prion-like RBPs such as TDP-43 and FUS exhibit age-dependent mislocalisation, nuclear depletion, and cytoplasmic aggregation, contributing to splicing defects, impaired RNA transport, and neurodegeneration in amyotrophic lateral sclerosis, frontotemporal dementia, and limbic-predominant age-related TDP-43 encephalopathy. Interactions between RBPs and non-coding RNAs, together with disrupted liquid-liquid phase separation dynamics, further exacerbate age-related decline. By integrating mechanistic studies from cellular and animal models with observations in human cohorts, this review underscores RBPs as central nodes linking multiple ageing hallmarks and highlights their potential as biomarkers and therapeutic targets to promote healthy ageing. Limitations of current models and priorities for future translational research are discussed.},
}

@article {pmid42351263,
year = {2026},
author = {Riggio, F and Fenili, G and Caporossi, D and Paronetto, MP},
title = {Dynamic integration of skeletal muscle signals via extracellular vesicles in motor neuron diseases.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02356-1},
pmid = {42351263},
issn = {2051-5960},
support = {PNRR-MR1-2022-12376821//Ministero della Salute/ ; },
abstract = {Extracellular vesicles (EVs) are heterogenous lipid bilayer-enclosed particles secreted by virtually all cell types. They encapsulate a diverse array of bioactive molecules, including proteins, lipids, nucleic acids, and metabolites, which can be transferred to recipient cells, thereby modulating their function and phenotype. In recent years, skeletal muscle-derived EVs (SkM-EVs) have emerged as key players in the bidirectional communication between skeletal muscle and motor neurons, contributing to the establishment and maintenance of neuromuscular homeostasis. Disruptions in this intercellular signalling have been implicated in the pathophysiology of motor neuron diseases (MNDs) such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). In these contexts, SkM-EVs may contribute to disease progression by delivering pathogenic cargo, including misfolded proteins and aberrant RNAs, to motor neurons. A comprehensive understanding of SkM-EV biology, particularly their roles in neuromuscular communication, could offer critical insights into disease mechanisms and identify novel opportunities for biomarker discovery and therapeutic intervention. This review synthesizes current knowledge on the functional roles of SkM-EVs in motor neuron health and disease and evaluates their potential as diagnostic tools and therapeutic vectors in the context of MNDs.},
}

@article {pmid42352309,
year = {2026},
author = {Morciano, G and Gorgoglione, R and Porcelli, V and Ahmed, A and Scarcia, P and Vozza, A and Lasorsa, FM and Fiermonte, G and Palmieri, L},
title = {Mitochondrial Dynamics and SLC25 Transporters in Neurodegeneration: From Mechanisms to Therapeutic Opportunities.},
journal = {Biomolecules},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/biom16060842},
pmid = {42352309},
issn = {2218-273X},
support = {2020RRJP5L//Ministry of Universities and Research/ ; 2022ZY7ATN//Ministry of Universities and Research/ ; GR-2019-12369862//Italian Ministry of Health/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/pathology/drug therapy ; *Mitochondrial Dynamics ; *Mitochondria/metabolism ; Animals ; *Mitochondrial Proteins/metabolism ; Energy Metabolism ; Mitochondrial Membrane Transport Proteins/metabolism ; },
abstract = {Neurodegenerative diseases are increasingly recognized as disorders of due to disrupted cellular homeostasis, with mitochondrial dysfunction playing a central and early role in disease progression. This review explores the intricate relationship between mitochondrial function and neuronal health, emphasizing the pivotal role of the solute carrier family 25 (SLC25) transporters in maintaining mitochondrial homeostasis. We provide a comprehensive overview of mitochondrial biology in the central nervous system, including energy metabolism, calcium signaling, redox regulation, organelle interactions and mitochondrial dynamics. We delve into the SLC25 transporter family, highlighting their transport mechanisms, substrates and roles in brain metabolism and neuroprotection. SLC25 on one hand and proteins involved in the regulation of mitochondrial morphology and calcium signaling on the other hand are two sides of the same coin influencing each other. A critical analysis follows, examining how mitochondrial dysfunction contributes to mitochondrial abnormalities in a spectrum of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, ALS and rare mitochondrial encephalopathies. Finally, we assess emerging therapeutic strategies targeting mitochondrial pathways and SLC25 function, including metabolic modulation, gene therapies, antioxidants and pharmacological agents. This review underscores mitochondria and the SLC25 transporters as promising targets for disease-modifying interventions in neurodegeneration and raises key questions about the causality between mitochondrial failure and neuronal death.},
}

Humans
*Neurodegenerative Diseases/metabolism/pathology/drug therapy
*Mitochondrial Dynamics
*Mitochondria/metabolism
Animals
*Mitochondrial Proteins/metabolism
Energy Metabolism
Mitochondrial Membrane Transport Proteins/metabolism

@article {pmid42352358,
year = {2026},
author = {Lee, BC and Hwang, JJ and Tsai, HJ},
title = {Extracellular Pgk1 or Its Derived Short Peptide Interacted with Membrane-Associated Enolase 2 Receptor: A Potential Therapy for ALS Motor Neuron Degeneration.},
journal = {Biomolecules},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/biom16060893},
pmid = {42352358},
issn = {2218-273X},
support = {NSTC-114-2313-B-030-001//National Science and Technology Council/ ; F630410//USA FJCU Alumni Foundation/ ; CPL-202508003//Collaborative Research Project between FJUH and FJU/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology ; Humans ; *Phosphopyruvate Hydratase/metabolism ; Animals ; *Phosphoglycerate Kinase/metabolism ; *Motor Neurons/metabolism/pathology/drug effects ; *Peptides/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) remains an intractable motor neuron (MN) disease with a growing patient population and few effective treatments. Here, we review how extracellular phosphoglycerate kinase 1 (ePgk1) improves neurite outgrowth of MNs (NOMN) and axonal growth, both in vitro and in vivo. Our group first elucidated a novel non-canonical function of ePgk1 as a cross-tissue mediator between nerve and muscle tissues. We then discovered that neural membranous Enolase 2 (Eno2) serves as a receptor of ligand ePgk1 and that ePgk1-Eno2 interaction suppresses the Rac1-GTP/p-Pak1-T423/p-P38-T180/pMK2-T334/p-Limk1-S323 axis, reducing p-Cofilin and promoting NOMN and axonal growth, finally suggesting that the 419th aspartic acid residue of Eno2 mediates this interaction. In a crucial preclinical step, we truncated two short 16-amino-acid derivatives from Pgk1, FD-1/-2, each mediating neuroprotection comparable to that of full-length 417-amino-acid Pgk1 in ALS animal models, in terms of improvements of innervated neuromuscular junction, MN cell bodies, motor performance, and endpoint prolongation. In this context, we also discuss the opposite function driven by Eno1-plasminogen interaction and by Eno2-ePgk1 interaction; the latter results in unfavorable for tumorigenesis. Unlike intracellular Pgk1 roles, ePgk1 is an extracellular factor with anti-angiogenic properties, further positioning ePgk1 and its FD-1/-2 as promising protein/peptide drugs for ALS treatment.},
}

*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology
Humans
*Phosphopyruvate Hydratase/metabolism
Animals
*Phosphoglycerate Kinase/metabolism
*Motor Neurons/metabolism/pathology/drug effects
*Peptides/metabolism

@article {pmid42352620,
year = {2026},
author = {De Luca, E and Saba, A and Bertarini, L and Brusini, A and Artioli, G and Dellafiore, F},
title = {Spiritual Care Needs and Challenges Among Caregivers and Families of People with Neurodegenerative Diseases in Palliative and End-of-Life Care: A Scoping Review.},
journal = {Brain sciences},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/brainsci16060611},
pmid = {42352620},
issn = {2076-3425},
abstract = {Background/Objectives: Spirituality is increasingly recognised as a core dimension of holistic and palliative care. Neurodegenerative diseases such as dementia, amyotrophic lateral sclerosis and Parkinson's disease involve prolonged trajectories of loss, uncertainty and relational change, which may heighten spiritual and existential needs for patients, particularly among those involved in caregiving, such as family caregivers and, to a lesser extent, healthcare professionals. However, evidence on how spirituality is understood, experienced and addressed within neurodegenerative palliative care remains fragmented and conceptually heterogeneous. This scoping review aimed to map the literature on caregivers' spiritual needs and challenges. Methods: A scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews (PRISMA ScR). Searches were conducted across PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), APA PsycINFO, and Scopus, with no date or geographical restrictions. Grey literature was searched through Google Scholar and relevant organisational and policy sources in the field of palliative care and spirituality. Reference list screening of included studies and relevant reviews was also conducted. Quantitative, qualitative, and mixed methods studies published in English or Italian were included. Results: Twenty-four studies published between 2007 and 2025 were included. Findings were organised into three interconnected domains: spiritual needs, spiritual processes and spiritual care. Spirituality emerged as a dynamic, relational and context-dependent dimension of caregiving, encompassing meaning, identity, connection and coping with vulnerability and loss. Spiritual needs and processes were widely described, while spiritual care was inconsistently recognised within healthcare systems. Conceptual ambiguity, under-representation of end-of-life dementia and cultural imbalances were evident. The evidence predominantly focused on family caregivers, with limited representation of healthcare professionals. Conclusions: This scoping review highlights a persistent gap between caregivers' lived spiritual experiences and system-level responses in neurodegenerative palliative care in caregiving contexts globally. The findings support integrated, caregiver-inclusive and culturally responsive approaches to spiritual care.},
}

@article {pmid42352907,
year = {2026},
author = {Scrivo, A and Bernardino, L and Consiglio, A},
title = {The Dual Role of Glial Extracellular Vesicles in Neurodegeneration: Insights from iPSC-Based Models.},
journal = {International journal of molecular sciences},
volume = {27},
number = {12},
pages = {},
doi = {10.3390/ijms27125182},
pmid = {42352907},
issn = {1422-0067},
support = {2023 BP 00242//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; },
abstract = {Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication in the brain, with glial cell-derived EVs increasingly recognized for their roles in maintaining brain homeostasis and contributing to the progression of neurodegenerative diseases. By transferring a diverse cargo of bioactive molecules, including proteins, RNAs, and organelles, EVs influence recipient cell behavior and overall brain function. In neurodegenerative conditions, glial EVs can either propagate pathogenic signals or deliver neuroprotective and regenerative cues, depending on their cellular origin and molecular composition. This context-dependent heterogeneity highlights the need for physiologically relevant human models to investigate EVs biology. Human induced pluripotent stem cell (iPSC)-derived glial models provide a disease-relevant platform, as they recapitulate key pathological features of Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). When further integrated with brain organoid platforms, these iPSC-based systems enable the generation of three-dimensional environments that closely resemble in vivo EVs dynamics. Importantly, glial EVs can modulate cellular pathways involved in neuronal survival and function. Indeed, their potential to interact with and, under specific experimental conditions, traverse the blood-brain barrier (BBB) has contributed to growing interest in their application for biomarker discovery and therapeutic development. Engineered and patient-specific EVs derived from iPSCs are emerging as promising tools for targeted, cell type-specific, therapeutic approaches, although their clinical applicability still requires further validation. This review discusses the emerging evidence supporting the dual role of iPSC-derived glial EVs in health and disease, underscores the translational potential of iPSC-based platforms for mechanistic studies, and outlines their promise as precision medicine tools for diagnostics and therapy.},
}

@article {pmid42353250,
year = {2026},
author = {Sharma, N and An, SSA},
title = {Microglial Dysfunction Induced by C9ORF72 Dipeptide Repeat Proteins: Biomarker and Therapeutic Perspectives.},
journal = {International journal of molecular sciences},
volume = {27},
number = {12},
pages = {},
doi = {10.3390/ijms27125537},
pmid = {42353250},
issn = {1422-0067},
support = {RS-2021-NR060117//National Research Foundation of Korea/ ; RS-2025-02292973//Korea Institute of Marine Science and Technology Promotion/ ; },
mesh = {*C9orf72 Protein/genetics/metabolism ; Humans ; *Microglia/metabolism/pathology ; Biomarkers/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/therapy ; *Frontotemporal Dementia/genetics/metabolism/pathology/therapy ; *Dipeptides/genetics/metabolism ; Animals ; DNA Repeat Expansion ; Autophagy ; },
abstract = {The GGGGCC hexanucleotide repeat expansion (HRE) in C9ORF72 was recognized as the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat-associated non-AUG (RAN) translation of the expanded repeat generated dipeptide repeat proteins (DPRs), which disrupted multiple cellular processes and contributed to neurodegeneration. Emerging evidence indicated that disease pathogenesis involved both gain-of-function (GOF) and loss-of-function (LOF) mechanisms. DPR-mediated GOF toxicity induced ribosomal dysfunction, nucleolar stress, proteostatic impairment, and neuronal injury, whereas C9ORF72 LOF disrupted lysosomal and autophagic pathways in microglia, impairing the immune homeostasis. Neuronal injury further promoted the release of damage-associated signals that triggered secondary microglial activations and chronic neuroinflammations. This review summarized current knowledge of DPR biology, microglial dysfunction, and their contributions to disease progression in C9ORF72-associated ALS/FTD. Therapeutic strategies targeting repeated RNA, DPR productions, proteostasis, autophagy, and neuroinflammatory pathways were also discussed. In addition, the potentials of fluid biomarkers, including cerebrospinal fluid poly (GP) and blood neurofilament light chain (NfL), for diagnosis, disease monitoring, and therapeutic assessment were shown. Together, these findings provided important insights into disease mechanisms and potential avenues for improved clinical management.},
}

*C9orf72 Protein/genetics/metabolism
Humans
*Microglia/metabolism/pathology
Biomarkers/metabolism
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology/therapy
*Frontotemporal Dementia/genetics/metabolism/pathology/therapy
*Dipeptides/genetics/metabolism
Animals
DNA Repeat Expansion
Autophagy

@article {pmid42357346,
year = {2026},
author = {Costanzi, E and Fontana, L and Giroldo, F and Coco, S},
title = {Advancing MSC-EV Therapies: Harnessing Preconditioning and Mito-EVs to Tackle Neuroinflammation and Neurodegeneration.},
journal = {Pharmaceutics},
volume = {18},
number = {6},
pages = {},
doi = {10.3390/pharmaceutics18060730},
pmid = {42357346},
issn = {1999-4923},
support = {P2022LR49L//Ministry of Universities and Research/ ; 202229X8HW//Ministry of Universities and Research/ ; },
abstract = {Neuroinflammation plays a central role in the onset and progression of neurodegenerative disorders. Several disease-modifying therapies have been developed to target neuroinflammatory pathways in specific disorders. However, their ability to stop disease progression or restore neuronal and mitochondrial homeostasis remains limited. This is still a major unmet clinical need. In this context, mesenchymal stromal cell (MSC)-derived Extracellular Vesicles (EVs) have emerged as a promising cell-free therapeutic strategy due to their ability to modulate immune responses and promote neuroprotection through the delivery of bioactive cargo. Recent evidence has identified a distinct subset of EVs, known as mitochondrial EVs (mito-EVs), which carry mitochondrial DNA, proteins, and functional components. These vesicles may uniquely influence cellular bioenergetics, redox balance, and neuroinflammatory signaling, offering additional therapeutic potential compared to conventional MSC-EVs. This review summarizes the role of MSC-derived EVs in neuroinflammatory disorders, with a particular focus on mito-EVs. It also discusses preconditioning strategies to enhance EV efficacy, including hypoxic, inflammatory, pharmacological priming and genetic engineering approaches. Finally, we critically evaluate current preclinical evidence regarding the treatment of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis, as well as Traumatic Injury, highlighting the key challenges for clinical translation.},
}

@article {pmid42358489,
year = {2026},
author = {Lepski, G and Arévalo, A},
title = {Mesenchymal stromal/stem cells for neurological disorders in humans: an evidence-mapped clinical review.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1844360},
pmid = {42358489},
issn = {1662-5102},
abstract = {Mesenchymal stromal/stem cells (MSCs) have been tested clinically across a wide spectrum of neurological disorders, motivated by their immunomodulatory and trophic ("bystander") mechanisms rather than durable neural replacement. Here, we synthesize human prospective clinical trials that administered MSC products for neurological indications, prioritizing study design/goals, disease stage/severity, cell source/manufacturing, dose/route, detailed clinical assessments, quantified score changes, and adverse events (AEs). Across indications, trials frequently demonstrate feasibility and short-term safety, while efficacy signals are heterogeneous and strongly dependent on disease stage and endpoint selection criteria. The most methodologically rigorous signals with quantified motor outcomes include stereotactic intracerebral implantation of SB623 for chronic motor deficits after traumatic brain injury (TBI). In amyotrophic lateral sclerosis (ALS), randomized evidence supports safety and early slope-based signals in selected subgroups after intrathecal MSC regimens, but durable clinical benefit remains unproven. In hypoxic-ischemic encephalopathy (HIE), controlled data suggest functional improvements in small cohorts, and neonatal studies support feasibility adjunctive to hypothermia. We highlight design features most likely to de-risk efficacy interpretation: adequately powered randomized controlled trials, disease-stage stratification, prespecified clinically meaningful change thresholds, standardized rehabilitation co-interventions, and transparent AE adjudication.},
}

@article {pmid42359165,
year = {2026},
author = {Morimoto, S and Kato, C and Takahashi, S and Okano, H},
title = {Therapeutic frontiers in ALS: iPSC-based drug discovery, cell therapy, and gene therapy-Advances through 2026.},
journal = {Regenerative therapy},
volume = {33},
number = {},
pages = {101150},
pmid = {42359165},
issn = {2352-3204},
abstract = {Three converging therapeutic paradigms-iPSC-based drug discovery, cell transplantation, and gene therapy-have substantially expanded the therapeutic pipeline for amyotrophic lateral sclerosis (ALS) between 2020 and 2026. The FDA's accelerated approval of tofersen (Qalsody) in April 2023 marked the first treatment targeting a genetic cause of ALS. iPSC-derived drug candidates, including ropinirole and bosutinib, have completed early-phase clinical trials led by Japanese institutions. Cell therapies targeting neuroinflammation through regulatory T cells are being actively explored as immunomodulatory strategies, although efficacy remains to be established in adequately powered trials. Next-generation gene-silencing approaches-including RNA interference (RNAi) therapeutics and AAV-delivered microRNA-entered first-in-human trials in 2024-2025. The identification of STMN2 as a downstream target of TDP-43 dysfunction has opened a potential TDP-43-downstream nucleic acid therapeutic avenue for sporadic ALS, which constitutes approximately 90% of all cases, with company-reported interim data suggesting target engagement in the ongoing Phase 1/2 ANQUR trial (QRL-201). This review synthesizes the latest evidence across all three therapeutic domains, with attention to the hierarchy of evidence, regulatory milestones, and the pioneering contributions of Japanese research groups.},
}

@article {pmid42359357,
year = {2026},
author = {Shu, X and Yu, X and Xu, P and Wang, A},
title = {Innate immune crosstalk in ALS/FTD pathogenesis.},
journal = {Cell insight},
volume = {5},
number = {4},
pages = {100340},
pmid = {42359357},
issn = {2772-8927},
abstract = {Marked by protein aggregation, impaired proteostasis, organelle stress, and chronic neuroinflammation, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) form a clinically, genetically, and pathologically overlapping disease spectrum. Increasing evidence indicates that innate immune activation is not merely a secondary response to neuronal injury, but an active driver of disease progression. In this review, we elaborate on how ALS/FTD-associated genetic lesions and pathogenic protein aggregates, including TDP-43, SOD1, FUS, and C9orf72-derived dipeptide repeat proteins, engage three interconnected innate immune pathways: cGAS-STING, NLRP3 inflammasomes, and TREM2-DAP12 signaling. We further highlight emerging crosstalk among these pathways, in which cGAS-STING and NLRP3 reinforce inflammatory signaling, while NLRP3-driven TREM2 shedding may impair microglial clearance and perpetuate proteostatic failure. Understanding this immune network may help define disease subtypes, identify biomarkers, and guide combinatorial therapeutic strategies that suppress harmful inflammation while preserving protective microglial functions.},
}

@article {pmid42359947,
year = {2026},
author = {Rozman, SI and Hamzaid, NA and Lim, E and Hamzah, N},
title = {Noninvasive assessment of cardiovascular autonomic reflexes in amyotrophic lateral sclerosis: a systematic review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/21678421.2026.2692135},
pmid = {42359947},
issn = {2167-9223},
abstract = {Dysautonomia is gradually recognized in amyotrophic lateral sclerosis (ALS), raising concerns of secondary complications from heightened autonomic burden. Autonomic disturbances, particularly cardiac dysautonomia, significantly impact patient outcomes, contributing to increased cardiovascular risks and mortality rate. While the ALS Functional Rating Score-Revised (ALSFRS-R) measures functional decline as disease progress, it overlooks autonomic criteria - a critical factor in ALS progression. This review aims to analyze noninvasive applications of cardiovascular signal variability for continuous real-time monitoring of autonomic dysfunction in ALS, while addressing gaps in current clinical assessments. A total of 584 literatures were gathered from four databases (WoS, PubMed, Science Direct and MEDLINE EBSCOhost) - published from inception till December 2023. 21 peer-reviewed studies were included in this review after screening and meeting the inclusion criteria. Various cardiovascular signal variability metrics and autonomic protocols were discussed. Key findings highlight cardiac autonomic dysfunction in ALS is marked by reduced heart rate variability, absent blood pressure regulation upon orthostatic stress and circadian changes, prolonged QTc interval and low baroreflex sensitivity. Moreover, increased autonomic burden is associated with a shift from sympathetic to parasympathetic dysregulation as the disease progresses. Evidence highlights the need to integrate noninvasive autonomic biomarkers into digital ALS monitoring frameworks, enabling earlier detection of autonomic involvement and more precise longitudinal monitoring beyond motor decline.},
}

@article {pmid42360551,
year = {2026},
author = {Pramanik, S and Debnath, B and Chakraborty, A and Islam, A and Mullick, S and Chaudhary, P and Nath, R and Chellappan, DK and Mondal, M and Ashique, S},
title = {Targeting mtDNA to Modulate Mitochondrial Dysfunction in Neurodegenerative Diseases.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42360551},
issn = {1559-1182},
mesh = {Humans ; *Neurodegenerative Diseases/genetics/therapy/pathology ; *DNA, Mitochondrial/genetics/metabolism ; Animals ; *Mitochondria/genetics/metabolism/pathology ; Gene Editing ; },
abstract = {Mitochondrial dysfunction is a common pathological feature of neurodegenerative diseases namely Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Although these disorders are primarily driven by disease-specific genetic and proteopathic mechanisms, increasing evidence suggests that secondary mitochondrial DNA (mtDNA) damage and heteroplasmy shifts may exacerbate bioenergetic failure and neuronal vulnerability. Distinguishing primary disease mechanisms from downstream mtDNA alterations is critical to accurately evaluate emerging therapeutic strategies. Recent advances in mtDNA-targeted genome editing have enabled the direct manipulation of mitochondrial genomes. Mitochondrially targeted zinc finger nucleases and TALENs can selectively alter mutant mtDNA to induce heteroplasmy shifts, whereas DddA-derived cytosine base editors allow precise base editing without double-strand breaks. However, each platform has distinct limitations related to the target scope, off-target risk, design complexity, and delivery efficiency. The application of CRISPR/Cas-based systems to mammalian mtDNA remains constrained by the unresolved challenges in guiding RNA import. This review critically examines mitochondrial dysfunction and mutant mtDNA accumulation in neurodegenerative diseases. It also evaluates current and emerging mtDNA-editing techniques, and highlights key translational barriers. We highlighted that mtDNA-targeted interventions can be a promising approach for disease-modifying or adjunctive strategies, rather than curative approaches.},
}

Humans
*Neurodegenerative Diseases/genetics/therapy/pathology
*DNA, Mitochondrial/genetics/metabolism
Animals
*Mitochondria/genetics/metabolism/pathology
Gene Editing

@article {pmid42361623,
year = {2026},
author = {Deptuła, P and Chmielewska-Deptuła, S and Spałek, J and Kaliniak, S and Okła, S and Bucki, R},
title = {Decoding the pathogenesis of Candida albicans infection and evaluating the efficacy of antifungal drugs using atomic force microscopy.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {201},
number = {},
pages = {119705},
doi = {10.1016/j.biopha.2026.119705},
pmid = {42361623},
issn = {1950-6007},
abstract = {Atomic force microscopy (AFM) has emerged as a pivotal method enabling multidimensional characterization of Candida albicans (C. albicans) by simultaneously providing topographical imaging, mechanical profiling, and quantitative measurements of adhesion forces under near-physiological conditions. AFM-derived data demonstrate that nanoscale surface alterations, including wrinkling, indentations, increased roughness, and perforations correlate closely with modulation of the Young's modulus and with the reorganization of mannoproteins and adhesins, particularly those of the Als family. The co-occurrence of structural, mechanical, and adhesive changes reflects the dynamic remodeling of the fungal cell wall that governs morphogenesis, virulence, and biofilm formation. AFM offers high resolution insight into the mechanisms of action of antifungal drugs, antimicrobial peptides, nanomaterials, and physical treatments that destabilize the cell wall, reduce its stiffness, or conversely induce compensatory stiffening and adhesin exposure. As a result, the technique enables the identification of critical steps in stress responses and hyperadhesive phenotypes that contribute to fungal invasion and treatment resistance. Integration of AFM with spectroscopic and microfluidic approaches further enhances its potential to reveal new therapeutic targets. Collectively, evidence from numerous studies underscores AFM as a foundational tool in the rational design of modern, multimodal antifungal strategies aimed at the cell wall and biofilm of C. albicans.},
}

@article {pmid42345500,
year = {2026},
author = {Drążyk, M and Pyc, Z and Pietrzyk, SJ and Gajda-Janiak, A and Godziszewski, F and Pioterek, O and Tulski, M and Mazurek, M and Domagała, ZA},
title = {Formaldehyde neurotoxicity: Effects on the mammalian brain, cognitive function, and neurodegenerative risk. A scoping review.},
journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University},
volume = {},
number = {},
pages = {},
doi = {10.17219/acem/209617},
pmid = {42345500},
issn = {1899-5276},
abstract = {Aqueous formaldehyde (FA) solution, known as formalin, is currently the primary agent used for preserving tissue samples and anatomical specimens. Formaldehyde is widely used in laboratories and the chemical industry; it also occurs as an air pollutant and endogenous cellular metabolite. The potential carcinogenic effects of formalin on the respiratory tract are well documented. A less recognized consequence of occupational exposure to FA is its detrimental effect on the central nervous system (CNS) and brain function. A literature review was conducted to investigate the effects of FA on the brain. Five databases were searched: PubMed, Web of Science (WoS), Embase, ScienceDirect, and Google Scholar. To describe the effects of FA exposure and endogenous FA generation, 35 relevant publications were collected and analyzed. The literature review demonstrated that inhalation is the most common route of FA exposure. Several studies have shown that FA may cause hippocampal damage, disrupt melatonin secretion, and induce a wide range of cognitive disorders with varying characteristics and severity. These disorders include memory impairment, disturbances in balance and spatial orientation, learning difficulties, sleep disturbances, impaired judgment, and prolonged reaction times to stimuli. Increased endogenous FA concentration has also been associated with a higher risk of neurodegenerative diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis. The literature analysis demonstrated the high neurotoxicity of FA, which may lead to numerous neuropsychiatric disorders. We aim to draw attention to the risks associated with the routine use of formalin, particularly among anatomists and pathologists, and to encourage consideration of less harmful alternative preservation agents.},
}

@article {pmid42160515,
year = {2026},
author = {Zhang, M and Yang, W and Wang, J and Zou, B and Zheng, JC and Wu, Q and Gao, G},
title = {Immunotherapeutic landscape of amyotrophic lateral sclerosis: A bibliometric analysis of research trends, translational priorities, and collaboration networks (2006-2025).},
journal = {Human vaccines & immunotherapeutics},
volume = {22},
number = {1},
pages = {2664985},
pmid = {42160515},
issn = {2164-554X},
mesh = {*Amyotrophic Lateral Sclerosis/therapy/immunology ; Humans ; *Immunotherapy/methods/trends ; *Bibliometrics ; *Translational Research, Biomedical/trends ; Animals ; Superoxide Dismutase-1/immunology ; C9orf72 Protein/genetics/immunology ; Microglia/immunology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) remains a major therapeutic challenge, with immune dysregulation increasingly recognized as a critical driver of disease progression. Despite extensive mechanistic research, no immunotherapeutic approach has achieved consistent disease-modifying effects, raising questions about whether this translational gap reflects biological complexity or structural misalignment within the research ecosystem. To characterize the intellectual evolution of ALS immunotherapeutics research, identify immune targets with translational potential, and evaluate collaboration patterns that may influence translational efficiency, we performed a bibliometric analysis of 2,256 publications indexed in Web of Science and Scopus using network-based approaches including co-citation clustering, keyword co-occurrence, and citation burst detection implemented in CiteSpace, VOSviewer, and R-Bibliometrix. Publication output increased 8.4-fold over the study period, delineating three developmental phases. Thematic analyses revealed a shift from early emphasis on microglial biology and SOD1-based models toward recent focus areas including the gut-brain axis, C9orf72-associated immune dysregulation, and advanced immunomodulatory strategies. Collaboration networks remain predominantly regional despite strong contributions from the United States, Europe, and Asia, with limited integration between mechanistic research groups and clinical trial consortia. Among immune-directed therapeutic strategies, regulatory T cell modulation and microglial-targeted approaches exhibit the highest translational readiness. These findings suggest that the lack of effective ALS immunotherapeutics reflects not only biological complexity but also structural and strategic misalignment within the research ecosystem. This bibliometric analysis provides a systems-level framework to guide more integrated translational strategies in ALS immunotherapeutics development.},
}

*Amyotrophic Lateral Sclerosis/therapy/immunology
Humans
*Immunotherapy/methods/trends
*Bibliometrics
*Translational Research, Biomedical/trends
Animals
Superoxide Dismutase-1/immunology
C9orf72 Protein/genetics/immunology
Microglia/immunology

@article {pmid42332177,
year = {2026},
author = {Tang, M and Fleming, E and Gu, J and Shi, H and Xu, Y and Gong, X},
title = {Trace Elements Dyshomeostasis and Toxic Metals Neurotoxicity in Neurodegenerative Diseases.},
journal = {Biological trace element research},
volume = {},
number = {},
pages = {},
pmid = {42332177},
issn = {1559-0720},
support = {Grant No. SH2023078//the Zhenjiang Science and Technology Plan Project/ ; Grant No. JDYY2023009//the Medical Education Collaborative Innovation Fund of Jiangsu University/ ; Grant No. 32002235//the National Natural Science Foundation of China/ ; },
abstract = {Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, are defined by the progressive loss of neurons through interconnected pathological mechanisms, including oxidative stress, mitochondrial dysfunction, protein aggregation, and neuroinflammation. Accumulating evidence implicates metal dyshomeostasis as a central and multifaceted contributor to these mechanisms, with roles ranging from a primary pathogenic driver in AD and PD, to a secondary amplifier of genetic pathology in HD and ALS, and as a contextual risk modifier in the presence of toxic metals. Essential trace metals such as iron, zinc, copper, manganese, selenium, iodine, and molybdenum are vital for neurotransmission, antioxidant defense, and cellular metabolism. Dysregulation of these metals disrupts redox balance, impairs proteostasis, and activates regulated cell death pathways, including ferroptosis and cuproptosis. Toxic metals, such as lead, cadmium, and mercury, exacerbate neurodegeneration by displacing essential metals, inducing oxidative injury, and promoting protein misfolding and neuroinflammation. This narrative review synthesizes mechanistic, experimental, genetic epidemiological, and clinical evidence to critically evaluate the contributions of both essential and toxic metals to neurodegeneration in AD, PD, HD, and ALS. We examine the genetic, environmental, and physiological determinants of metal homeostasis; the analytical techniques for quantifying metals in clinical samples; and clinical trial data on metal-targeted therapeutic strategies. Notably, iron chelation with deferiprone consistently reduces brain iron on neuroimaging but worsens clinical outcomes in both PD and AD, presenting a translational paradox that requires mechanistic re-evaluation. We also provide methodological recommendations for interpreting Mendelian randomization studies of metal exposures and propose translational priorities to advance metal-targeted diagnostics and therapeutics for neurodegenerative diseases.},
}

@article {pmid42341897,
year = {2026},
author = {Hopkins, EL and Williams, PA},
title = {Programmed axon degeneration gene variants in human disease.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115891},
doi = {10.1016/j.expneurol.2026.115891},
pmid = {42341897},
issn = {1090-2430},
abstract = {BACKGROUND: Programmed axon degeneration (PAD; also known as Wallerian degeneration) is a conserved pathway controlling axon breakdown following injury or metabolic stress. PAD is driven by the depletion of nicotinamide adenine dinucleotide (NAD) through loss of the pro-survival enzyme NMNAT2 and activation of the pro-degenerative NADase SARM1. Recent genetic studies have identified pathogenic variants in PAD pathway enzymes associated with severe neurodegenerative phenotypes.

MAIN BODY: Pathogenic variants in NAMPT, NMNAT1, NMNAT2, and SARM1 have been identified and will be discussed in this review. NAMPT variants cause sensory and motor neuropathy with neurodevelopmental symptoms. NMNAT1 variants are well-characterized causes of Leber Congenital Amaurosis type 9, while NMNAT2 variants result in peripheral neuropathies with childhood onset. SARM1 gain-of-function variants with constitutively active NADase activity are enriched in amyotrophic lateral sclerosis patients.

CONCLUSION: These findings demonstrate that maintaining proper NAD homeostasis is crucial for axon survival, and disruption through genetic variants leads to distinct neurodegenerative outcomes. Understanding these rare variants provides insight into PAD mechanisms and supports development of broad-spectrum neuroprotective therapies targeting this pathway. Current therapeutic approaches include SARM1 inhibitors in clinical trials, gene therapy, and NAD precursor supplementation, offering hope for treating multiple neurodegenerative diseases.},
}

@article {pmid42082894,
year = {2026},
author = {Kipourgos, G and Bakalis, N and Albani, E and Stefanopoulos, N and Lakoumentas, J and Tzenalis, A},
title = {Expert Consensus on Key Attributes of Nurses in Resuscitation Teams: Findings From a Delphi Study.},
journal = {Nursing in critical care},
volume = {31},
number = {3},
pages = {e70506},
pmid = {42082894},
issn = {1478-5153},
mesh = {Humans ; Delphi Technique ; *Clinical Competence ; *Heart Arrest/nursing/therapy ; Consensus ; Greece ; *Patient Care Team ; *Resuscitation ; *Cardiopulmonary Resuscitation/nursing ; Female ; Male ; },
abstract = {BACKGROUND: In-hospital cardiac arrest (IHCA) requires coordinated interdisciplinary action. Nurses are often first responders and essential members of resuscitation teams, yet the attributes that define their effectiveness remain unclear. Although team performance has been widely studied, few works have systematically examined nursing competencies in this context. This is the first Delphi-based study in Greece defining key nursing attributes within in-hospital resuscitation teams.

AIM: To achieve expert consensus on the key attributes characterizing effective nursing participation in IHCA teams.

STUDY DESIGN: A two-round Delphi study was conducted with experts in resuscitation and critical care. Round one involved thematic analysis of semi-structured interviews. In round two, experts rated attributes on a 10-point Likert scale. Consensus was defined as mean (M) > 8 and coefficient of variation (CV) < 20%. Descriptive statistics and Kendall's W assessed agreement across domains.

RESULTS: Thirty-nine attributes were identified and grouped into seven domains: education, experience, physical condition, psychological resilience, technical skills and non-technical skills. Thirty-five attributes met the consensus criteria. Highest agreement was observed for ALS certification, stress resilience, closed-loop communication, adaptability and teamwork. Strongest consensus emerged in non-technical (M = 9.75, CV = 3.79%) and technical (M = 9.61, CV = 5.62%) domains.

CONCLUSIONS: This study provides an evidence-informed framework of competencies and personal qualities underpinning nurses' effectiveness in resuscitation teams, emphasizing both technical expertise and non-technical skills-especially closed-loop communication, composure and collaboration.

The framework supports clearer role delineation, structured competency development and enhanced team effectiveness in IHCA management.},
}

Humans
Delphi Technique
*Clinical Competence
*Heart Arrest/nursing/therapy
Consensus
Greece
*Patient Care Team
*Resuscitation
*Cardiopulmonary Resuscitation/nursing
Female
Male

@article {pmid42229507,
year = {2026},
author = {Swanson, E and Dohle, E and Bashford, L and Horsfall, HL and Jovanovic, L and Muirhead, WR and Brannigan, JFM},
title = {Recalibration of implantable brain-computer interfaces to enable long-term independent use-a systematic review.},
journal = {Journal of neural engineering},
volume = {23},
number = {3},
pages = {},
doi = {10.1088/1741-2552/ae7694},
pmid = {42229507},
issn = {1741-2552},
mesh = {Humans ; *Brain-Computer Interfaces/standards ; Calibration ; *Electrodes, Implanted/standards ; },
abstract = {Background.Implantable brain-computer interfaces (iBCIs) decode neural signals to generate command signals for effector devices to restore lost functions, such as movement or speech. However, maintaining device performance over time requires recalibration of decoding algorithms due to inherent instability in neural signals.Objective.To systematically review recalibration procedures in iBCIs for patients with motor impairments, focusing on the clinical implications of recalibration requirements and strategies which can enable long-term, independent use.Approach.A systematic search was conducted across EMBASE, MEDLINE, and CINAHL databases to identify studies involving recalibration of iBCIs. Data on recalibration frequency, duration, staff requirements, and location were extracted and analyzed.Main results.Recalibration practices varied widely amongst studies and were typically performed according to predetermined study protocols, rather than practical need following deteriorating device performance. Common practices include manual recalibration requiring a specialist research team, semi-automatic recalibration which could be performed by a non-specialist caregiver, and automatic recalibration methods whereby patients did not require assistance. Devices utilizing electrocorticography (ECoG) recording arrays generally required less frequent recalibration compared to those using microelectrode arrays (MEAs). Extended independent use was more frequently reported with ECoG-based iBCIs.Significance.Reducing recalibration frequency or complexity can improve patient autonomy, which is crucial for enhancing long-term independent iBCI use in home and clinical settings. ECoG iBCIs typically have a low recalibration burden due to inherent signal stability. Conversely, MEA iBCIs typically involve a higher recalibration burden, though recent studies have reduced this by incorporating spectral data and continuously updating models. Despite this progress, recalibration procedures are often not fully defined in iBCI studies, and where they are, they usually relate to the study protocol rather than the clinically meaningful recalibration requirement due to worsening device performance. Future studies should continue to develop user-friendly recalibration procedures and outline the clinically relevant recalibration requirements where possible.},
}

Humans
*Brain-Computer Interfaces/standards
Calibration
*Electrodes, Implanted/standards

@article {pmid42329964,
year = {2026},
author = {Fernandes, APM and Bertucci Borges, LH and Holanda, LJ and Bezerra, BHES and Lopes, ACSM and Silva, MCFD and Valentim, RAM and Bougrain, L and Vasiljevic, GAM and Rodrigues Lindquist, AR},
title = {Applications of electromyography in Amyotrophic Lateral Sclerosis: A systematic review.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0350029},
pmid = {42329964},
issn = {1932-6203},
mesh = {*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Humans ; *Electromyography/methods ; Motor Neurons/physiology ; Muscle, Skeletal/physiopathology ; },
abstract = {This systematic review examined the use of surface electromyography (sEMG) for the neuromuscular assessment of individuals with Amyotrophic Lateral Sclerosis (ALS), focusing on clinical parameters, the muscle groups evaluated, acquisition protocols, technical properties of the recording systems, integration with other technologies, and signal processing strategies. We included observational studies that applied sEMG to individuals diagnosed with ALS, with or without comparison to healthy controls, and without restrictions on publication year. The analyses included signals recorded at rest and during voluntary contractions, with or without the use of biofeedback. Most studies employed conventional or high-density surface electrodes, with sampling frequencies ranging from 500 Hz to 3000 Hz. The results showed that the primary parameters assessed were muscle fatigue, fasciculation patterns, the number of motor units (MUNE/MUNIX), motor unit firing rates, and signal complexity. These parameters demonstrated sensitivity to disease progression and may contribute to early diagnosis, phenotypic stratification, and functional monitoring of ALS. Additionally, the studies highlighted the increasing use of advanced computational approaches, such as machine learning, for feature extraction and automated classification. In conclusion, sEMG is a promising tool for functional assessment in ALS, with the potential to improve diagnostic accuracy and support new therapeutic strategies based on electrophysiological biomarkers. However, despite technological advances, the included studies displayed substantial methodological heterogeneity and limited protocol standardization. Integration with other neurophysiological modalities also remains underexplored, despite its significant clinical potential.},
}

*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis
Humans
*Electromyography/methods
Motor Neurons/physiology
Muscle, Skeletal/physiopathology

@article {pmid41974458,
year = {2026},
author = {Facciabene, A and Ellsworth, SG},
title = {Gut-targeted strategies at the intersection of radiotherapy and immunotherapy.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {4},
pages = {},
pmid = {41974458},
issn = {2051-1426},
mesh = {Humans ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/radiation effects/drug effects/immunology ; *Neoplasms/immunology/therapy/radiotherapy ; Animals ; *Radiotherapy/methods ; Host-Directed Therapy ; },
abstract = {The gut microbiota has emerged as a critical determinant of therapeutic immunity, shaping responses to immune checkpoint inhibitors, adoptive cellular therapies, and radiotherapy (RT). Interest has grown in whether interventions targeting the microbiota might deliberately amplify anticancer immunity.Chen and colleagues recently proposed an unconventional approach: using low-dose intestinal irradiation (ILDR) to remodel the gut microbiota and thereby enhance responsiveness to programmed death-ligand 1 blockade in patients with metastatic cancer. Their report, though preliminary, suggests that directed RT to the intestine can in fact act to favorably modulate the intestinal microbiota. Importantly, current evidence remains largely correlative and does not establish a causal relationship between ILDR, microbiota remodeling, and enhanced systemic antitumor immunity. This concept is provocative, but it raises fundamental questions: does gut-directed RT truly enhance systemic antitumor immunity, or might additional confounding variables, organ-specific effects, and potential toxicities influence the signal?In this Commentary, we balance enthusiasm with caution. We first outline the conceptual framework linking RT, microbiota, and immune activation; then highlight the specific pitfalls revealed by Chen et al's study, including challenges in attribution, heterogeneity, and immunosuppression. We also discuss complementary translational approaches, including direct microbiota modulation through targeted antibiotics and other gut-directed strategies, as potential tools to experimentally interrogate the microbiota-RT-immunotherapy axis in patients.},
}

Humans
*Immunotherapy/methods
*Gastrointestinal Microbiome/radiation effects/drug effects/immunology
*Neoplasms/immunology/therapy/radiotherapy
Animals
*Radiotherapy/methods
Host-Directed Therapy

@article {pmid42328245,
year = {2026},
author = {Dong, J and Lu, M and Chen, Y and Zisman-Ilani, Y and Feng, Y and Zhang, S and Huang, H and Zhou, Y},
title = {Bridging the Gap Between Efficacy and Practice: A Systematic Review of Shared Decision-Making in Severe Mental Illness.},
journal = {Journal of multidisciplinary healthcare},
volume = {19},
number = {},
pages = {610845},
pmid = {42328245},
issn = {1178-2390},
abstract = {Shared decision-making (SDM) is recommended for preference-sensitive treatment decisions in severe mental illness, but its routine use in psychiatric services remains inconsistent. This systematic review synthesized evidence published between 2014 and 2024 and examined clinical, cultural, and organizational factors associated with SDM implementation. We searched PubMed, Embase, CINAHL, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP for studies published from January 2014 to November 2024. Forty-two studies involving 8798 participants were included. Reporting followed PRISMA 2020 and SWiM guidance. Study quality was assessed with design-specific Joanna Briggs Institute tools, and certainty of key findings was appraised using a combined GRADE-CERQual approach. Because of heterogeneity in study design, interventions, outcomes, and settings, findings were synthesized narratively using Popay et al's framework. Patient decision aids were generally associated with lower decisional conflict, greater readiness, satisfaction, involvement, or autonomy, with little evidence of meaningful consultation-time extension. Clinician training and SDM interventions improved short-term engagement and information sharing, but evidence for sustained improvements in adherence, decisional conflict, and clinician behavior was mixed or low certainty. Family-mediated or triadic decision-making was prominent in East and Southeast Asian studies and may support adherence and participation, although it can also create tension between patient autonomy and family preferences. Across studies, clinicians and patients often emphasized different treatment priorities, particularly symptom control versus side-effect tolerability. Evidence was concentrated in Europe and East Asia, with limited data from low-resource regions. SDM in psychiatric care appears most reliable for improving immediate decision processes rather than long-term outcomes. Future implementation should test culturally adapted triadic decision aids, workflow-integrated prompts, and interprofessional decision coaching while using cautious, context-sensitive outcome evaluation.},
}

@article {pmid42329291,
year = {2026},
author = {Sathick Batcha, BR and Amarnath, DP and Srinivasan, D and Ramakrishnan, P},
title = {Targeting mitochondrial dysfunction and neuroprotection in neurodegenerative disorders: emerging therapeutic potential of berberine and polymeric nanoparticle-based delivery systems.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42329291},
issn = {1568-5608},
abstract = {Major neurodegenerative disorders, such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, are pathologically driven by mitochondrial failure and persistent neuroinflammation. Defects in oxidative phosphorylation, excess Reactive Oxygen Species (ROS), and impaired mitophagy cause an imbalance in neuronal energy and promote the release of mitochondrial Damage-Associated Molecular Patterns (DAMPs) that activate microglial inflammasomes and enhance inflammatory signalling. Current therapeutic strategies have largely targeted individual pathways and have been unable to effectively modulate this interrelated mitochondrial immune axis or achieve efficient delivery to the Central Nervous System (CNS). This review addresses the dual promise of berberine therapy, a biologically active plant alkaloid that enhances mitochondrial production via AMPK/PGC-1α and SIRT1, restores membrane potential, promotes mitophagy, and inhibits NF-κB and NLRP3-mediated inflammation. Nevertheless, this compound's weak solubility, limited bioavailability, and extremely poor Blood-Brain Barrier (BBB) penetration limit its therapeutic application. Encapsulation of berberine in polymeric nanoparticles, including Polyethylene glycol (PEG)-based polymeric nanoparticle systems, offers improved stability, bioavailability, and targeted mitochondrial delivery. An effective method for reducing neuroinflammation and mitochondrial dysfunction is this comprehensive phytochemical nanotechnology technique.},
}

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

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

@article {pmid40272376,
year = {2025},
author = {Nguyen, THV and Ferron, F and Murakami, K},
title = {Neurotoxic Implications of Human Coronaviruses in Neurodegenerative Diseases: A Perspective from Amyloid Aggregation.},
journal = {ACS chemical biology},
volume = {20},
number = {5},
pages = {983-992},
doi = {10.1021/acschembio.5c00153},
pmid = {40272376},
issn = {1554-8937},
mesh = {Humans ; *Neurodegenerative Diseases/virology/metabolism ; *Amyloid/metabolism/chemistry ; *Coronavirus/metabolism/pathogenicity ; *Coronavirus Infections/complications/virology ; },
abstract = {Human coronaviruses (HCoVs) include seven species: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV, SARS-CoV-1, and SARS-CoV-2. The last three, classified as Betacoronaviruses, are highly transmissible and have caused severe pandemics. HCoV infections primarily affect the respiratory system, leading to symptoms such as dry cough, fever, and breath shortness, which can progress to acute respiratory failure and death. Beyond respiratory effects, increasing evidence links HCoVs to neurological dysfunction. However, distinguishing direct neural complications from preexisting disorders, particularly in the elderly, remains challenging. This study examines the association between HCoVs and neurodegenerative diseases like Alzheimer disease, Parkinson disease, Lewy body dementia, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. It also presents the long-term neurological effects of HCoV infections and their differential impact across age groups and sexes. A key aspect of this study is the investigation of the sequence and structural similarities between amyloidogenic and HCoV spike proteins, which can provide insights into potential neuropathomechanisms.},
}

Humans
*Neurodegenerative Diseases/virology/metabolism
*Amyloid/metabolism/chemistry
*Coronavirus/metabolism/pathogenicity
*Coronavirus Infections/complications/virology

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

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

@article {pmid40278411,
year = {2025},
author = {Di Sarno, A and Romano, F and Arianna, R and Serpico, D and Lavorgna, M and Savastano, S and Colao, A and Di Somma, C},
title = {Lipid Metabolism and Statin Therapy in Neurodegenerative Diseases: An Endocrine View.},
journal = {Metabolites},
volume = {15},
number = {4},
pages = {},
pmid = {40278411},
issn = {2218-1989},
abstract = {Background/aim: A growing body of evidence suggests a link between dyslipidemias and neurodegenerative diseases, highlighting the crucial role of lipid metabolism in the health of the central nervous system. The aim of our work was to provide an update on this topic, with a focus on clinical practice from an endocrinological point of view. Endocrinologists, being experts in the management of dyslipidemias, can play a key role in the prevention and treatment of neurodegenerative conditions, through precocious and effective lipid profile optimization. Methods: The literature was scanned to identify clinical trials and correlation studies on the association between dyslipidemia, statin therapy, and the following neurodegenerative diseases: Alzheimer's disease (AD), Parkisons's disease (PD), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). Results: Impaired lipid homeostasis, such as that frequently observed in patients affected by obesity and diabetes, is related to neurodegenerative diseases, such as AD, PD, and other cognitive deficits related to aging. AD and related dementias are now a real priority health problem. In the United States, there are approximately 7 million subjects aged 65 and older living with AD and related dementias, and this number is projected to grow to 12 million in the coming decades. Lipid-lowering therapy with statins is an effective strategy in reducing serum low-density lipoprotein cholesterol to normal range concentrations and, therefore, cardiovascular disease risk; moreover, statins have been reported to have a positive effect on neurodegenerative diseases. Conclusions: Several pieces of research have found inconsistent information following our review. There was no association between statin use and ALS incidence. More positive evidence has emerged regarding statin use and AD/PD. However, further large-scale prospective randomized control trials are required to properly understand this issue.},
}

@article {pmid40279084,
year = {2026},
author = {Singh, P and Borkar, M and Doshi, G},
title = {Network pharmacology approach to unravel the neuroprotective potential of natural products: a narrative review.},
journal = {Molecular diversity},
volume = {30},
number = {1},
pages = {59-100},
pmid = {40279084},
issn = {1573-501X},
mesh = {Humans ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Biological Products/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Network Pharmacology/methods ; Animals ; Aging ; },
abstract = {Aging is a slow and irreversible biological process leading to decreased cell and tissue functions with higher risks of multiple age-related diseases, including neurodegenerative diseases. It is widely accepted that aging represents the leading risk factor for neurodegeneration. The pathogenesis of these diseases involves complex interactions of genetic mutations, environmental factors, oxidative stress, neuroinflammation, and mitochondrial dysfunction, which complicate treatment with traditional mono-targeted therapies. Network pharmacology can help identify potential gene or protein targets related to neurodegenerative diseases. Integrating advanced molecular profiling technologies and computer-aided drug design further enhances the potential of network pharmacology, enabling the identification of biomarkers and therapeutic targets, thus paving the way for precision medicine in neurodegenerative diseases. This review article delves into the application of network pharmacology in understanding and treating neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and spinal muscular atrophy. Overall, this article emphasizes the importance of addressing aging as a central factor in developing effective disease-modifying therapies, highlighting how network pharmacology can unravel the complex biological networks associated with aging and pave the way for personalized medical strategies.},
}

Humans
*Neuroprotective Agents/pharmacology/therapeutic use
*Biological Products/pharmacology/therapeutic use
*Neurodegenerative Diseases/drug therapy/metabolism
*Network Pharmacology/methods
Animals
Aging

@article {pmid40280271,
year = {2025},
author = {Kopalli, SR and Behl, T and Baldaniya, L and Ballal, S and Joshi, KK and Arya, R and Chaturvedi, B and Chauhan, AS and Verma, R and Patel, M and Jain, SK and Wal, A and Gulati, M and Koppula, S},
title = {Neuroadaptation in neurodegenerative diseases: compensatory mechanisms and therapeutic approaches.},
journal = {Progress in neuro-psychopharmacology & biological psychiatry},
volume = {139},
number = {},
pages = {111375},
doi = {10.1016/j.pnpbp.2025.111375},
pmid = {40280271},
issn = {1878-4216},
mesh = {Humans ; *Neurodegenerative Diseases/therapy/physiopathology/metabolism/pathology ; *Neuronal Plasticity/physiology ; Animals ; *Adaptation, Physiological/physiology ; *Brain/physiopathology/pathology/metabolism ; },
abstract = {Progressive neuronal loss is a hallmark of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS), which cause cognitive and motor impairment. Delaying the onset and course of symptoms is largely dependent on neuroadaptation, the brain's ability to restructure in response to damage. The molecular, cellular, and systemic processes that underlie neuroadaptation are examined in this study. These mechanisms include gliosis, neurogenesis, synaptic plasticity, and changes in neurotrophic factors. Axonal sprouting, dendritic remodelling, and compensatory alterations in neurotransmitter systems are important adaptations observed in NDDs; nevertheless, these processes may shift to maladaptive plasticity, which would aid in the advancement of the illness. Amyloid and tau pathology-induced synaptic alterations in Alzheimer's disease emphasize compensatory network reconfiguration. Dopamine depletion causes a major remodelling of the basal ganglia in Parkinson's disease, and non-dopaminergic systems compensate. Both ALS and Huntington's disease rely on motor circuit rearrangement and transcriptional dysregulation to slow down functional deterioration. Neuroadaptation is, however, constrained by oxidative stress, compromised autophagy, and neuroinflammation, particularly in elderly populations. The goal of emerging therapy strategies is to improve neuroadaptation by pharmacologically modifying neurotrophic factors, neuroinflammation, and synaptic plasticity. Neurostimulation, cognitive training, and physical rehabilitation are instances of non-pharmacological therapies that support neuroplasticity. Restoring compensating systems may be possible with the use of stem cell techniques and new gene treatments. The goal of future research is to combine biomarkers and individualized medicines to maximize neuroadaptive responses and decrease the course of illness. In order to reduce neurodegeneration and enhance patient outcomes, this review highlights the dual function of neuroadaptation in NDDs and its potential as a therapeutic target.},
}

Humans
*Neurodegenerative Diseases/therapy/physiopathology/metabolism/pathology
*Neuronal Plasticity/physiology
Animals
*Adaptation, Physiological/physiology
*Brain/physiopathology/pathology/metabolism

@article {pmid40280282,
year = {2025},
author = {Matsuda, KM and Kotani, H and Sato, S and Yoshizaki, A},
title = {Unveiling the hidden syndrome: The enigma of anti-transcobalamin receptor autoantibodies.},
journal = {Immunology letters},
volume = {275},
number = {},
pages = {107028},
doi = {10.1016/j.imlet.2025.107028},
pmid = {40280282},
issn = {1879-0542},
mesh = {Humans ; *Autoantibodies/immunology ; *Autoimmune Diseases/immunology ; Vitamin B 12/therapeutic use ; Animals ; *Vitamin B 12 Deficiency/immunology ; Syndrome ; *Antigens, CD/immunology ; *Receptors, Cell Surface/immunology ; },
abstract = {The transcobalamin receptor (CD320) functions as a critical mediator for vitamin B12 uptake in cells, with emerging evidence linking autoantibodies against CD320 to various autoimmune conditions. Pluvinage et al.'s recent study identified anti-CD320 autoantibodies as a cause of autoimmune vitamin B12 central deficiency, specifically affecting the central nervous system while sparing peripheral nerves. Their findings align with our previous work showing anti-CD320's role in cutaneous arteritis. Both studies identified overlapping CD320 epitopes targeted by autoantibodies and demonstrated the therapeutic efficacy of high-dose vitamin B12 supplementation in mitigating symptoms. Expanding on these findings, we observed anti-CD320 autoantibodies in other inflammatory disorders such as systemic sclerosis, suggesting a broader clinical relevance. The work by Pluvinage et al. and our group supports the concept of an "anti-CD320-associated syndrome," with high-dose B12 supplementation as a promising treatment strategy. Further research is needed to fully elucidate the tissue-specific mechanisms and pathophysiology underlying these autoimmune conditions.},
}

Humans
*Autoantibodies/immunology
*Autoimmune Diseases/immunology
Vitamin B 12/therapeutic use
Animals
*Vitamin B 12 Deficiency/immunology
Syndrome
*Antigens, CD/immunology
*Receptors, Cell Surface/immunology

@article {pmid40280464,
year = {2025},
author = {Gritsiuta, AI and Reep, G and Parupudi, S and Petrov, RV},
title = {Optimizing the management of anastomotic leaks after esophagectomy: a narrative review of salvage strategies and outcomes.},
journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract},
volume = {29},
number = {7},
pages = {102069},
doi = {10.1016/j.gassur.2025.102069},
pmid = {40280464},
issn = {1873-4626},
mesh = {Humans ; *Esophagectomy/adverse effects ; *Anastomotic Leak/therapy/etiology ; *Salvage Therapy/methods ; Drainage/methods ; Treatment Outcome ; Nutritional Support ; Anti-Bacterial Agents/therapeutic use ; },
abstract = {BACKGROUND: Anastomotic leaks (ALs) after esophagectomy remain a major postoperative complication, leading to increased morbidity, prolonged hospital stays, and higher mortality. Despite advancements in surgical techniques and perioperative care, AL management lacks standardized protocols. This review aimed to evaluate current salvage strategies, including conservative, endoscopic, and surgical approaches, to optimize outcomes and reduce complications.

METHODS: A comprehensive literature search was conducted using PubMed, Scopus, Cochrane Library, and Google Scholar databases to identify studies published between 2000 and 2025 on AL management after esophagectomy. Peer-reviewed clinical trials, guidelines, and expert consensus reports were reviewed, focusing on minimally invasive and surgical interventions, patient outcomes, and emerging treatment strategies.

RESULTS: AL management strategies were classified into 3 primary approaches. Conservative management includes nutritional support, antibiotic therapy, and percutaneous drainage, particularly for contained leaks. Endoscopic interventions, such as self-expanding metal stents and endoscopic vacuum-assisted closure, have shown high success rates, with vacuum-assisted closure achieving superior closure outcomes. Hybrid techniques, including stent-over-sponge and vacuum-assisted closure-stent, are emerging as promising alternatives. Surgical interventions remain the gold standard for severe or refractory leaks with options, including primary repair, esophageal diversion, and delayed conduit reconstruction.

CONCLUSION: A multidisciplinary approach is crucial for optimizing AL management, incorporating enhanced recovery protocols, early risk assessment, and individualized treatment plans. Endoscopic techniques have reduced the need for surgical revisions, but surgical intervention remains necessary for severe cases. Future research should focus on refining treatment algorithms, integrating novel technologies, and establishing standardized guidelines to improve patient survival and quality of life.},
}

Humans
*Esophagectomy/adverse effects
*Anastomotic Leak/therapy/etiology
*Salvage Therapy/methods
Drainage/methods
Treatment Outcome
Nutritional Support
Anti-Bacterial Agents/therapeutic use

@article {pmid40281300,
year = {2025},
author = {Upadhayay, S and Soni, D and Dhureja, M and Temgire, P and Kumar, V and Arthur, R and Kumar, P},
title = {Role of Fibroblast Growth Factors in Neurological Disorders: Insight into Therapeutic Approaches and Molecular Mechanisms.},
journal = {Molecular neurobiology},
volume = {62},
number = {11},
pages = {14367-14386},
pmid = {40281300},
issn = {1559-1182},
mesh = {Humans ; *Nervous System Diseases/metabolism/therapy/drug therapy ; Animals ; *Fibroblast Growth Factors/metabolism ; Signal Transduction/physiology ; },
abstract = {In the last few decades, the incidence and progression of neurological disorders have consistently increased, which mainly occur due to environmental pollution, genetic abnormalities, and modern lifestyles. Several case reports suggested that these factors enhanced oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis, leading to neurological disease. The pathophysiology of neurological disorders is still not understood, mainly due to the diversity within affected populations. Existing treatment options primarily provide symptomatic relief but frequently come with considerable side effects, including depression, anxiety, and restlessness. Fibroblast growth factors (FGFs) are key signalling molecules regulating various cellular functions, including cell proliferation, differentiation, electrical excitability, and injury responses. Hence, several investigations claimed a relationship between FGFs and neurological disorders, and their findings indicated that they could be used as therapeutic targets for neurological disorders. The FGFs are reported to activate various signalling pathways, including Ras/MAPK/PI3k/Akt, and downregulate the GSK-3β/NF-κB pathways responsible for anti-oxidant, anti-inflammatory, and anti-apoptotic effects. Therefore, researchers are interested in developing novel treatment options for neurological disorders. The emergence of unreported FGFs contributes to our understanding of their involvement in these conditions and encourages further exploration of innovative therapeutic approaches. All the data were obtained from published articles using PubMed, Web of Science, and Scopus databases using the search terms Fibroblast Growth Factor, PD, HD, AD, ALS, signalling pathways, and neurological disorders.},
}

Humans
*Nervous System Diseases/metabolism/therapy/drug therapy
Animals
*Fibroblast Growth Factors/metabolism
Signal Transduction/physiology

@article {pmid40282367,
year = {2025},
author = {Watanabe, Y and Nakagawa, T and Nakagawa, M and Nakayama, K},
title = {The Molecular Intersection of NEK1, C21ORF2, Cyclin F, and VCP in ALS Pathogenesis.},
journal = {Genes},
volume = {16},
number = {4},
pages = {},
pmid = {40282367},
issn = {2073-4425},
support = {23K06367//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; *NIMA-Related Kinase 1/genetics/metabolism ; *Valosin Containing Protein/genetics/metabolism ; *Cyclins/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Animals ; DNA Damage ; Mutation ; DNA Repair ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness, paralysis, and death. Although significant progress has been made in understanding ALS, its molecular mechanisms remain complex and multifactorial. This review explores the potential convergent mechanisms underlying ALS pathogenesis, focusing on the roles of key proteins including NEK1, C21ORF2, cyclin F, VCP, and TDP-43. Recent studies suggest that mutations in C21ORF2 lead to the stabilization of NEK1, while cyclin F mutations activate VCP, resulting in TDP-43 aggregation. TDP-43 aggregation, a hallmark of ALS, impairs RNA processing and protein transport, both of which are essential for neuronal function. Furthermore, TDP-43 has emerged as a key player in DNA damage repair, translocating to DNA damage sites and recruiting repair proteins. Given that NEK1, VCP, and cyclin F are also involved in DNA repair, this review examines how these proteins may intersect to disrupt DNA damage repair mechanisms, contributing to ALS progression. Impaired DNA repair and protein homeostasis are suggested to be central downstream mechanisms in ALS pathogenesis. Ultimately, understanding the interplay between these pathways could offer novel insights into ALS and provide potential therapeutic targets. This review aims to highlight the emerging connections between protein aggregation, DNA damage repair, and cellular dysfunction in ALS, fostering a deeper understanding of its molecular basis and potential avenues for intervention.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
*NIMA-Related Kinase 1/genetics/metabolism
*Valosin Containing Protein/genetics/metabolism
*Cyclins/genetics/metabolism
DNA-Binding Proteins/genetics/metabolism
Animals
DNA Damage
Mutation
DNA Repair

@article {pmid40283201,
year = {2025},
author = {González-Sánchez, M and Ramírez-Expósito, MJ and Martínez-Martos, JM},
title = {Pathophysiology, Clinical Heterogeneity, and Therapeutic Advances in Amyotrophic Lateral Sclerosis: A Comprehensive Review of Molecular Mechanisms, Diagnostic Challenges, and Multidisciplinary Management Strategies.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
pmid = {40283201},
issn = {2075-1729},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons, leading to muscle atrophy, paralysis, and respiratory failure. This comprehensive review synthesizes the current knowledge on ALS pathophysiology, clinical heterogeneity, diagnostic frameworks, and evolving therapeutic strategies. Mechanistically, ALS arises from complex interactions between genetic mutations (e.g., in C9orf72, SOD1, TARDBP (TDP-43), and FUS) and dysregulated cellular pathways, including impaired RNA metabolism, protein misfolding, nucleocytoplasmic transport defects, and prion-like propagation of toxic aggregates. Phenotypic heterogeneity, manifesting as bulbar-, spinal-, or respiratory-onset variants, complicates its early diagnosis, which thus necessitates the rigorous application of the revised El Escorial criteria and emerging biomarkers such as neurofilament light chain. Clinically, ALS intersects with frontotemporal dementia (FTD) in up to 50% of the cases, driven by shared TDP-43 pathology and C9orf72 hexanucleotide expansions. Epidemiological studies have revealed a lifetime risk of 1:350, with male predominance (1.5:1) and peak onset between 50 and 70 years. Disease progression varies widely, with a median survival of 2-4 years post-diagnosis, underscoring the urgency for early intervention. Approved therapies, including riluzole (glutamate modulation), edaravone (antioxidant), and tofersen (antisense oligonucleotide), offer modest survival benefits, while dextromethorphan/quinidine alleviates the pseudobulbar affect. Non-pharmacological treatment advances, such as non-invasive ventilation (NIV), prolong survival by 13 months and improve quality of life, particularly in bulb-involved patients. Multidisciplinary care-integrating physical therapy, respiratory support, nutritional management, and cognitive assessments-is critical to addressing motor and non-motor symptoms (e.g., dysphagia, spasticity, sleep disturbances). Emerging therapies show promise in preclinical models. However, challenges persist in translating genetic insights into universally effective treatments. Ethical considerations, including euthanasia and end-of-life decision-making, further highlight the need for patient-centered communication and palliative strategies.},
}

@article {pmid40283578,
year = {2025},
author = {Mantle, D and Hargreaves, I},
title = {Coenzyme Q10 and the Blood-Brain Barrier: An Overview.},
journal = {Journal of clinical medicine},
volume = {14},
number = {8},
pages = {},
pmid = {40283578},
issn = {2077-0383},
abstract = {Mitochondrial dysfunction is a common factor known to be involved in the pathogenesis of a number of neurological disorders, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Given the importance of coenzyme Q10 (CoQ10) in promoting normal mitochondrial function, and the deficiency of CoQ10 reported in such neurological disorders, there is a rationale for investigating the potential therapeutic role of supplementary CoQ10. However, while there is evidence for the efficacy of CoQ10 supplementation in animal models of the above disorders, randomised controlled clinical trials supplementing CoQ10 in PD, AD, or ALS have had disappointing outcomes. This in turn may be a reflection of the current uncertainty as to whether CoQ10 can access the blood-brain barrier in human subjects. In an attempt to further elucidate the disparity in outcomes of such preclinical and clinical studies, in this article we have reviewed evidence from the peer-reviewed literature to establish the ability of CoQ10 to access the brain via the BBB.},
}

@article {pmid40284554,
year = {2025},
author = {Tamai, R and Kiyoura, Y},
title = {Candida Infections: The Role of Saliva in Oral Health-A Narrative Review.},
journal = {Microorganisms},
volume = {13},
number = {4},
pages = {},
pmid = {40284554},
issn = {2076-2607},
support = {21K10233, 23K09511//KAKEN/ ; },
abstract = {Candida species, particularly Candida albicans, are causative agents of oral infections to which immunocompromised patients are especially susceptible. Reduced saliva flow (xerostomia) can lead to Candida overgrowth, as saliva contains antibacterial components such as histatins and β-defensins that inhibit fungal growth and adhesion to the oral mucosa. Candida adheres to host tissues, forms biofilms, and secretes enzymes required for tissue invasion and immune evasion. Secretory asparaginyl proteinases (Saps) and candidalysin, a cytolytic peptide toxin, are vital to Candida virulence, and agglutinin-like sequence (Als) proteins are crucial for adhesion, invasion, and biofilm formation. C. albicans is a risk factor for dental caries and may increase periodontal disease virulence when it coexists with Porphyromonas gingivalis. Candida infections have been suggested to heighten the risk of oral cancer based on a relationship between Candida species and oral squamous cell carcinoma (OSCC) or oral potentially malignant disorder (OPMD). Meanwhile, β-glucan in the Candida cell wall has antitumor effects. In addition, Candida biofilms protect viruses such as herpesviruses and coxsackieviruses. Understanding the intricate interactions between Candida species, host immune responses, and coexisting microbial communities is essential for developing preventive and therapeutic strategies against oral Candida infections, particularly in immunocompromised individuals.},
}

@article {pmid40287045,
year = {2025},
author = {Dudzisz, K and Wandzik, I},
title = {Antisense oligonucleotides: A promising advancement in neurodegenerative disease treatment.},
journal = {European journal of pharmacology},
volume = {999},
number = {},
pages = {177644},
doi = {10.1016/j.ejphar.2025.177644},
pmid = {40287045},
issn = {1879-0712},
mesh = {Humans ; *Oligonucleotides, Antisense/therapeutic use ; *Neurodegenerative Diseases/genetics/drug therapy/therapy ; Animals ; Clinical Trials as Topic ; },
abstract = {Antisense oligonucleotides (ASOs) are a class of therapeutics designed to modulate gene expression and have shown promise in the treatment of various neurodegenerative diseases. As of March 2025, four ASO-based therapies have received approval for the treatment of neurodegenerative diseases, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and hereditary transthyretin amyloidosis (ATTR). These approvals underscore the therapeutic potential of ASOs as effective treatments for neurodegenerative diseases by addressing specific genetic abnormalities. This is best demonstrated by clinical studies in more than a dozen ASOs, which could pave the way for the development of new therapeutics soon. Moreover, the ongoing extended clinical studies, which target presymptomatic carriers, have significant potential to cure familial ALS based on the SOD1 gene mutation. This review provides an update on clinical trials, highlighting promising results and the challenges encountered.},
}

Humans
*Oligonucleotides, Antisense/therapeutic use
*Neurodegenerative Diseases/genetics/drug therapy/therapy
Animals
Clinical Trials as Topic

@article {pmid40288591,
year = {2025},
author = {Servi, R and Akkoç, RF and Aksu, F and Servi, S},
title = {Therapeutic potential of enzymes, neurosteroids, and synthetic steroids in neurodegenerative disorders: A critical review.},
journal = {The Journal of steroid biochemistry and molecular biology},
volume = {251},
number = {},
pages = {106766},
doi = {10.1016/j.jsbmb.2025.106766},
pmid = {40288591},
issn = {1879-1220},
mesh = {Humans ; *Neurosteroids/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Steroids/therapeutic use ; *Neuroprotective Agents/therapeutic use/pharmacology ; Alzheimer Disease/drug therapy/metabolism ; },
abstract = {Neurodegenerative disorders present a significant challenge to healthcare systems, mainly due to the limited availability of effective treatment options to halt or reverse disease progression. Endogenous steroids synthesized in the central nervous system, such as pregnenolone (PREG), dehydroepiandrosterone (DHEA), progesterone (PROG), and allopregnanolone (ALLO), have been identified as potential therapeutic agents for neurodegenerative diseases. Neurosteroids such as ALLO, DHEA, and PROG, as well as their synthetic analogs like Ganaxolene, Fluasterone, and Olexoxime, offer promising effects for conditions such as Alzheimer's disease (AD) and depression. Moreover, Brexanolone and Ganaxolone are synthetic steroids approved for the treatment of postpartum depression and epilepsy, respectively. Neurosteroids such as ALLO are crucial in modulating GABAergic neurotransmission and reducing neuroinflammation. These compounds enhance the activity of GABA-A receptors, leading to increased inhibitory signaling in the brain, which can help regulate mood, cognition, and neuroprotection. Small clinical trials and observational studies indicate that ALLO may have cognitive benefits, but no large-scale, definitive meta-analysis confirms a 20 % improvement in AD patients. Mitochondrial dysfunction plays a vital role in the pathogenesis of numerous neurological diseases due to the high-energy demand and sensitivity of neurons to oxidative stress. Reduced mitochondrial function leads to amyloid-beta plaques and tau tangles accumulation in AD. In Parkinson's disease (PD), mitochondrial dysfunction resulting from the PINK1 or Parkin genes leads to energy deficiencies and the accumulation of toxic byproducts. Mutations in genes such as SOD1, C9orf72, and TDP-43 have been associated with mitochondrial dysfunction in amyotrophic lateral sclerosis (ALS). Moreover, studies on these neurodegenerative diseases suggest that inflammation is not merely a consequence of neurodegeneration but is also an essential factor in this process. Many neurological disorders involve multifaceted interactions between genetics, the environment, and immune responses, making it difficult to pinpoint their exact causes. Future research aims to overcome these hurdles through genetic advances, regenerative medicine, and personalized therapies. Cutting-edge technologies such as artificial intelligence and high-throughput screening are expected to accelerate drug discovery and improve diagnostic accuracy. Increasing collaboration between interdisciplinary fields such as bioinformatics, neuroscience, and immunology will lead to innovative treatment strategies. This comprehensive review discusses the therapeutic effects of enzymes, neurosteroids, and synthetic steroids in different neurodegenerative diseases, particularly AD, PD, ALS, and MS. Potential challenges in the therapeutic use of neurosteroids, such as the limited bioavailability and off-target effects of synthetic steroids, are also discussed, and an up-to-date and comprehensive review of the impact of these steroids on neurodegenerative disorders is presented.},
}

Humans
*Neurosteroids/therapeutic use/pharmacology
*Neurodegenerative Diseases/drug therapy/metabolism
Animals
*Steroids/therapeutic use
*Neuroprotective Agents/therapeutic use/pharmacology
Alzheimer Disease/drug therapy/metabolism

@article {pmid40290120,
year = {2025},
author = {Hong, Y and Song, Y and Wang, W and Shi, J and Chen, X},
title = {Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases.},
journal = {Genes & diseases},
volume = {12},
number = {4},
pages = {101437},
pmid = {40290120},
issn = {2352-3042},
abstract = {Neuronal death is associated with mitochondrial dysfunction caused by mutations in mitochondrial DNA. Mitochondrial DNA becomes damaged when processes such as replication, repair, and nucleotide synthesis are compromised. This extensive accumulation of damaged mitochondrial DNA subsequently disrupts the normal function of mitochondria, leading to aging, degeneration, or even death of neurons. Mitochondrial dysfunction stands as a pivotal factor in the development of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Recognizing the intricate nature of their pathogenesis, there is an urgent need for more effective therapeutic interventions. In recent years, mitochondrial DNA editing tools such as zinc finger nucleases, double-stranded DNA deaminase toxin A-derived cytosine base editors, and transcription activator-like effector ligand deaminases have emerged. Their emergence will revolutionize the research and treatment of mitochondrial diseases. In this review, we summarize the advancements in mitochondrial base editing technology and anticipate its utilization in neurodegenerative diseases, offering insights that may inform preventive strategies and therapeutic interventions for disease phenotypes.},
}

@article {pmid40294208,
year = {2025},
author = {Winek, K and Soreq, H},
title = {Emerging roles of transfer RNA fragments in the CNS.},
journal = {Brain : a journal of neurology},
volume = {148},
number = {8},
pages = {2631-2645},
pmid = {40294208},
issn = {1460-2156},
support = {5P01AG014449-21/GF/NIH HHS/United States ; 11183//Israel Science Foundation/ ; 835/23//Israel Science Foundation/ ; P01 AG014449/AG/NIA NIH HHS/United States ; 3213/19//Israel Science Foundation/ ; 1770/20//Israel Science Foundation/ ; },
mesh = {Humans ; *RNA, Transfer/metabolism/genetics ; Animals ; *Central Nervous System/metabolism ; *Central Nervous System Diseases/genetics/metabolism ; *RNA, Small Untranslated/metabolism/genetics ; },
abstract = {Transfer RNA-derived small RNAs (tsRNAs), previously considered inactive tRNA degradation products, have now been shown to be functional small non-coding RNAs. They may play important roles within the CNS and in brain-body interactions, both during normal developmental stages as well as in diverse brain pathologies. Among the cell types found in the CNS, tsRNAs are particularly abundant in neurons. Correspondingly, neurons show cell type specific tRNA expression profiles when compared to other cells of the CNS under homeostatic conditions and defects in tRNA processing may lead to neurological disorders. Disease-specific tsRNA profiles have been identified in a number of CNS disorders, including amyotrophic lateral sclerosis and epilepsy. Elevated levels of specific tsRNAs have been found in the blood before the onset of epileptic seizures; and age-related, sex-specific loss of mitochondrial genome-originated tsRNAs in the nucleus accumbens of female patients is correlated with accelerated cognitive deterioration in Alzheimer's disease. Disease-related tsRNA signatures have also been identified in the CSF of patients with Parkinson's disease, and nucleated blood cells from ischaemic stroke patients show specific elevation of cholinergic-targeted tsRNAs. The mechanisms of action of tsRNAs are still being elucidated but include targeting complementary mRNA to impact RNA levels and translation in a miRNA-like manner, direct interaction with RNA binding proteins, or interference with translation machinery. The function of tsRNAs may be affected by the chemical modifications they inherit from the originating tRNA molecules, which impact tsRNAs production and may modulate their interactions with proteins. Research on the genetics, biochemical properties and regulatory roles of tsRNAs has expanded rapidly in recent years, facilitated by novel sequencing strategies, which include the removal of tRNA modifications and chemically blocked ends that hinder amplification and adapter ligation. Future in-depth profiling of tsRNAs levels, mode(s) of function, and identification of interacting proteins and RNAs may together shed light on the impact of tsRNAs on neuronal function, and enable novel diagnostics/therapeutics avenues for brain diseases in age, sex and disease-specific manner.},
}

Humans
*RNA, Transfer/metabolism/genetics
Animals
*Central Nervous System/metabolism
*Central Nervous System Diseases/genetics/metabolism
*RNA, Small Untranslated/metabolism/genetics

@article {pmid40296625,
year = {2025},
author = {Barabadi, T and Mirjalili, ES and Mohamadi-Zarch, SM and Rahimi, H and Keshmirshekan, F and Bagheri, SM},
title = {Cell-Free DNA, a Noninvasive Biomarker for Prediction and Detection of Neurodegenerative Diseases, New Insights, and Perspectives.},
journal = {CNS & neurological disorders drug targets},
volume = {24},
number = {10},
pages = {731-742},
pmid = {40296625},
issn = {1996-3181},
support = {18535//Shahid Sadoughi University of Medical Science and Health Services/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/blood ; Biomarkers/blood ; *Cell-Free Nucleic Acids/blood/metabolism ; Parkinson Disease/diagnosis ; Animals ; },
abstract = {Neurodegenerative diseases pose serious threats to public health worldwide. Biomarkers for neurodegenerative disorders are essential to enhance the diagnostic process in clinical settings and to aid in the creation and assessment of effective disease-modifying treatments. In recent times, affordable and readily available blood-based biomarkers identifying the same neurodegenerative disease pathologies have been created, potentially transforming the diagnostic approach for these disorders worldwide. Emerging relevant biomarkers for α-synuclein pathology in Parkinson's disease include blood-based indicators of overall neurodegeneration and glial activation. Cell-free DNA (cfDNA), an encouraging non-invasive biomarker commonly utilized in oncology and pregnancy, has demonstrated significant potential in clinical uses for diagnosing neurodegenerative disorders. In this section, we explore the latest cfDNA studies related to neurodegenerative disorders. Moreover, we present a perspective on the possible role of cfDNA as a diagnostic, therapeutic, and prognostic indicator for neurodegenerative disorders. This review provides a summary of the most recent progress in biomarkers for neurodegenerative disorders such as Alzheimer's, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain injury.},
}

Humans
*Neurodegenerative Diseases/diagnosis/blood
Biomarkers/blood
*Cell-Free Nucleic Acids/blood/metabolism
Parkinson Disease/diagnosis
Animals

@article {pmid40298821,
year = {2025},
author = {Bortolotti, M and Polito, L and Battelli, MG and Bolognesi, A},
title = {Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {40298821},
issn = {2076-3921},
abstract = {Non-communicable neurological disorders are the second leading cause of death, and their burden continues to increase as the world population grows and ages. Oxidative stress and inflammation are crucially implicated in the triggering and progression of multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and even stroke. In this narrative review, we examine the role of xanthine oxidoreductase (XOR) activities and products in all the above-cited neurological diseases. The redox imbalance responsible for oxidative stress could arise from excess reactive oxygen and nitrogen species resulting from the activities of XOR, as well as from the deficiency of its main product, uric acid (UA), which is the pivotal antioxidant system in the blood. In fact, with the exception of stroke, serum UA levels are inversely related to the onset and progression of these neurological disorders. The inverse correlation observed between the level of uricemia and the presence of neurological diseases suggests a neuroprotective role for UA. Oxidative stress and inflammation are also caused by ischemia and reperfusion, a condition in which XOR action has been recognized as a contributing factor to tissue damage. The findings reported in this review could be useful for addressing clinical decision-making and treatment optimization.},
}

@article {pmid40299101,
year = {2025},
author = {Sarkar, S and Porel, P and Kosey, S and Aran, KR},
title = {Unraveling the role of CGRP in neurological diseases: a comprehensive exploration to pathological mechanisms and therapeutic implications.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {436},
pmid = {40299101},
issn = {1573-4978},
mesh = {Humans ; *Calcitonin Gene-Related Peptide/metabolism/genetics ; Animals ; Neuroprotective Agents/pharmacology/therapeutic use/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy/pathology ; *Nervous System Diseases/metabolism ; Signal Transduction ; Receptors, Calcitonin Gene-Related Peptide/metabolism ; Oxidative Stress ; },
abstract = {Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Spinal muscular atrophy (SMA) are neurodegenerative diseases (NDDs) characterized by progressive neuronal degeneration. Recent studies provide compelling information regarding the contribution of Calcitonin Gene-Related Peptide (CGRP), a potent neuropeptide, in regulating neuroinflammation, vasodilation, and neuronal survival in these disorders. This review systematically delves into the multidimensional aspects of CGRP as both a neuroprotective agent and a neurotoxic factor in NDDs. The neuroprotective effects of CGRP include suppression of inflammation, regulation of intracellular signaling pathways, and promotion of neuronal growth and survival. However, under pathological conditions, its overexpression or dysregulation is associated with oxidative stress, excitotoxicity, and neuronal death. The therapeutic use of CGRP and its receptor antagonists in migraine provides substantial evidence for CGRP's therapeutic potential, which can be further explored for the management of NDDs. However, since the bidirectional nature of CGRP effects is evident, it is crucial to gain an accurate insight into its mechanisms to target only the neuropeptide's beneficial effects while completely avoiding the undesired consequences. Further studies should focus on understanding the context-dependent activity of CGRP in the hope of designing targeted therapy for NDDs, which could gradually transform the current pharmacological management of NDDs.},
}

Humans
*Calcitonin Gene-Related Peptide/metabolism/genetics
Animals
Neuroprotective Agents/pharmacology/therapeutic use/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy/pathology
*Nervous System Diseases/metabolism
Signal Transduction
Receptors, Calcitonin Gene-Related Peptide/metabolism
Oxidative Stress

@article {pmid40299102,
year = {2025},
author = {Zhang, G and Huang, S and Wei, M and Wu, Y and Wang, J},
title = {Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.},
journal = {Neurochemical research},
volume = {50},
number = {3},
pages = {155},
pmid = {40299102},
issn = {1573-6903},
support = {2023JJB140089//Guangxi Youth Science Foundation Project/ ; 82201694//the National Natural Scientific Foundation of China/ ; 2022AC21033//Guangxi Science and technology base and talent project/ ; 2022KY0349//Guangxi university young and middle-aged teachers' basic ability improvement project/ ; },
mesh = {Humans ; Animals ; *Nervous System Diseases/metabolism/drug therapy ; *Glutamate Plasma Membrane Transport Proteins/metabolism ; Glutamic Acid/metabolism ; },
abstract = {Excitatory amino acid transporters (EAATs) are pivotal regulators of glutamate homeostasis in the central nervous system and orchestrate synaptic glutamate clearance through transmembrane transport and the glutamine‒glutamate cycle. The five EAAT subtypes (GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3, EAAT4, and EAAT5) exhibit spatiotemporal-specific expression patterns in neurons and glial cells, and their dysfunction is implicated in diverse neurological pathologies, including epilepsy, amyotrophic lateral sclerosis (ALS), schizophrenia, depression, and retinal degeneration. Mechanistic studies revealed that astrocytic GLT-1 deficiency disrupts glutamate clearance in ALS motor neurons, whereas GLAST genetic variants are linked to both epilepsy susceptibility and glaucomatous retinal ganglion cell degeneration. Three major challenges persist in ongoing research: ① subtype-specific regulatory mechanisms remain unclear; ② compensatory functions of transporters vary significantly across disease models; and ③ clinical translation lacks standardized evaluation criteria. The interaction mechanisms and dynamic roles of EAATs in neurological disorders were systematically investigated in this study, and an integrated approach combining single-cell profiling, stem cell-based disease modeling, and drug screening platforms was proposed. These findings lay the groundwork for novel therapeutic strategies targeting glutamate homeostasis.},
}

Humans
Animals
*Nervous System Diseases/metabolism/drug therapy
*Glutamate Plasma Membrane Transport Proteins/metabolism
Glutamic Acid/metabolism

@article {pmid40299512,
year = {2025},
author = {Eslami, M and Adampour, Z and Fadaee Dowlat, B and Yaghmayee, S and Motallebi Tabaei, F and Oksenych, V and Naderian, R},
title = {A Novel Frontier in Gut-Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders.},
journal = {Biomedicines},
volume = {13},
number = {4},
pages = {},
pmid = {40299512},
issn = {2227-9059},
abstract = {The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.},
}

@article {pmid40299664,
year = {2025},
author = {Nogueira-Machado, JA and Rocha-Silva, F and Gomes, NA},
title = {The Role of mTOR in Amyotrophic Lateral Sclerosis.},
journal = {Biomedicines},
volume = {13},
number = {4},
pages = {},
pmid = {40299664},
issn = {2227-9059},
abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a rare, progressive, and incurable disease characterized by muscle weakness and paralysis. Recent studies have explored a possible link between ALS pathophysiology and mTOR signaling. Recent reports have linked the accumulation of protein aggregates, dysfunctional mitochondria, and homeostasis to the development of ALS. mTOR plays a pivotal role in controlling autophagy and affecting energy metabolism, in addition to supporting neuronal growth, plasticity, and the balance between apoptosis and autophagy, all of which are important for homeostasis. Aim: This mini-review approaches the regulatory roles of mTOR signaling pathways, their interaction with other metabolic pathways, and their potential to modulate ALS progression. Significance: It discusses how these metabolic signaling pathways affect the neuromuscular junction, producing symptoms of muscle weakness and atrophy similar to those seen in patients with ALS. The discussion includes the concepts of neurocentric and peripheral and the possible connection between mTOR and neuromuscular dysfunction in ALS. Conclusions: It highlights the therapeutic potential of mTOR signaling and interconnections with other metabolic routes, making it a promising biomarker and therapeutic target for ALS.},
}

@article {pmid40300213,
year = {2025},
author = {Sun, Y and Vermulst, M},
title = {The hidden costs of imperfection: transcription errors in protein aggregation diseases.},
journal = {Current opinion in genetics & development},
volume = {93},
number = {},
pages = {102350},
pmid = {40300213},
issn = {1879-0380},
support = {R01 AG054641/AG/NIA NIH HHS/United States ; R01 AG075130/AG/NIA NIH HHS/United States ; R01 AG083065/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Transcription, Genetic/genetics ; *Protein Aggregation, Pathological/genetics/pathology ; Protein Folding ; *Alzheimer Disease/genetics/pathology ; *Neurodegenerative Diseases/genetics/pathology ; *Protein Aggregates/genetics ; Amyloid/genetics ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Aging/genetics/pathology ; Prions/genetics ; Mutation ; },
abstract = {At first glance, biological systems appear to operate with remarkable precision and order. Yet, closer examination reveals that this perfection is an illusion, biological processes are inherently prone to errors. Here, we describe recent evidence that indicates that errors that occur during transcription play an important role in neurological diseases. These errors, though transient, can have lasting consequences when they generate mutant proteins with amyloid or prion-like properties. Such proteins can seed aggregation cascades, converting wild-type counterparts into misfolded conformations, ultimately leading to toxic deposits seen in diseases like Alzheimer's and amyotrophic lateral sclerosis. These observations help to paint a fuller picture of the origins of neurodegenerative diseases in aging humans and suggest a unified mechanism by which they may arise.},
}

Humans
*Transcription, Genetic/genetics
*Protein Aggregation, Pathological/genetics/pathology
Protein Folding
*Alzheimer Disease/genetics/pathology
*Neurodegenerative Diseases/genetics/pathology
*Protein Aggregates/genetics
Amyloid/genetics
*Amyotrophic Lateral Sclerosis/genetics/pathology
Aging/genetics/pathology
Prions/genetics
Mutation

@article {pmid40300556,
year = {2025},
author = {Zhou, S and Zhou, P and Yang, T and Si, J and An, W and Jiang, Y},
title = {Glucosamine supplementation contributes to reducing the risk of type 2 diabetes: Evidence from Mendelian randomization combined with a meta-analysis.},
journal = {The Journal of international medical research},
volume = {53},
number = {4},
pages = {3000605251334460},
pmid = {40300556},
issn = {1473-2300},
mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics/prevention & control/epidemiology ; *Glucosamine/administration & dosage/therapeutic use ; Mendelian Randomization Analysis ; *Dietary Supplements ; Genome-Wide Association Study ; Risk Factors ; Polymorphism, Single Nucleotide ; },
abstract = {ObjectiveObservational studies on glucosamine supplementation and type 2 diabetes risk have shown inconsistent results, necessitating the use of Mendelian randomization to clarify the true causal relationship.MethodsThe glucosamine supplementation-related genome-wide association study dataset was obtained from the MRC Integrative Epidemiology Unit consortium, whereas type 2 diabetes-related genome-wide association study datasets were obtained from the FinnGen consortium (discovery) and Xue et al.'s meta-analysis (validation). Two-sample Mendelian randomization analyses were performed separately in the discovery and validation datasets, followed by meta-analysis and multivariable Mendelian randomization analyses to verify the robustness of the results of two-sample Mendelian randomization. The estimation of the causal relationship was conducted through the inverse variance weighted method.ResultsGlucosamine supplementation exhibited a significant protective effect against type 2 diabetes, as identified by two-sample Mendelian randomization analysis in the FinnGen consortium (odds ratio: 0.13, 95% confidence interval: 0.02-0.89) and validated in Xue et al.'s meta-analysis (odds ratio: 0.06, 95%; confidence interval: 0.01-0.29). A combined meta-analysis (odds ratio: 0.08, 95%; confidence interval: 0.02-0.27) of the results of two-sample Mendelian randomization confirmed the robustness of these findings. Additionally, multivariable Mendelian randomization analysis (odds ratio: 0.12, 95%; confidence interval: 0.02-0.94), after adjusting for confounding factors, supported the results of two-sample Mendelian randomization. No evidence of heterogeneity or pleiotropy was observed.ConclusionOverall, our results revealed that genetically predicted glucosamine supplementation was inversely associated with the risk of type 2 diabetes, highlighting the potential importance of glucosamine supplementation in preventing type 2 diabetes.},
}

Humans
*Diabetes Mellitus, Type 2/genetics/prevention & control/epidemiology
*Glucosamine/administration & dosage/therapeutic use
Mendelian Randomization Analysis
*Dietary Supplements
Genome-Wide Association Study
Risk Factors
Polymorphism, Single Nucleotide

@article {pmid40300682,
year = {2025},
author = {Li, Z and Xing, J},
title = {Role of sirtuins in cerebral ischemia-reperfusion injury: Mechanisms and therapeutic potential.},
journal = {International journal of biological macromolecules},
volume = {310},
number = {Pt 4},
pages = {143591},
doi = {10.1016/j.ijbiomac.2025.143591},
pmid = {40300682},
issn = {1879-0003},
mesh = {Humans ; *Sirtuins/metabolism/genetics ; *Reperfusion Injury/metabolism/drug therapy/pathology ; Animals ; *Brain Ischemia/metabolism/drug therapy/pathology ; },
abstract = {The high incidence and mortality rate of cardiac arrest (CA) establishes it as a critical clinical challenge in emergency medicine globally. Despite continuous advances in advanced life support (ALS) technology, the prognosis for patients experiencing cardiac arrest remains poor, with cerebral ischemia and reperfusion injury (CIRI) being a significant determinant of adverse neurological outcomes and increased mortality. Sirtuins (SIRTs) are a class of highly evolutionarily conserved NAD[+]-dependent histone deacylenzymes capable of regulating the expression of various cytoprotective genes to play a neuroprotective role in CIRI. SIRTs mainly regulate the levels of downstream proteins such as PGC 1-α, Nrf 2, NLRP 3, FoxOs, and PINK 1 to inhibit inflammatory response, attenuate oxidative stress, improve mitochondrial dysfunction, promote angiogenesis, and inhibit apoptosis while reducing CIRI. Natural active ingredients are widely used in regulating the protein level of SIRTs in the body because of their multi-components, multi-pathway, multi-target, and minimal toxic side effects. However, these naturally active ingredients still face many challenges related to drug targeting, pharmacokinetic properties, and drug delivery. The emergence and vigorous development of new drug delivery systems, such as nanoparticles, micromilk, and exosomes, provide strong support for solving the above problems. In the context of the rapid development of molecular biology technology, non-coding RNA (NcRNA), represented by miRNA and LncRNA, offers great potential for achieving gene-level precision medicine. In the context of multidisciplinary integration, combining SIRTs proteins with biotechnology, omics technologies, artificial intelligence, and material science will strongly promote the deepening of their basic research and expand their clinical application. This review describes the major signaling pathways of targeting SIRTs to mitigate CIRI, as well as the current research status of Chinese and Western medicine and medical means for the intervention level of SIRTs. Meanwhile, the challenges and possible solutions in the clinical application of targeted drugs are summarized. In the context of medical and industrial crossover, the development direction of SIRTs in the future is discussed to provide valuable reference for basic medical researchers and clinicians to improve the clinical diagnosis and treatment effects of CIRI.},
}

Humans
*Sirtuins/metabolism/genetics
*Reperfusion Injury/metabolism/drug therapy/pathology
Animals
*Brain Ischemia/metabolism/drug therapy/pathology

@article {pmid40301152,
year = {2025},
author = {Armas, JMB and Taoro-González, L and Fisher, EMC and Acevedo-Arozena, A},
title = {Challenges of modelling TDP-43 pathology in mice.},
journal = {Mammalian genome : official journal of the International Mammalian Genome Society},
volume = {36},
number = {2},
pages = {465-481},
pmid = {40301152},
issn = {1432-1777},
mesh = {Animals ; *DNA-Binding Proteins/genetics/metabolism ; Mice ; *Disease Models, Animal ; *TDP-43 Proteinopathies/genetics/pathology/metabolism ; Humans ; Mutation ; Amyotrophic Lateral Sclerosis/genetics/pathology ; Cell Nucleus/genetics/metabolism ; Cytoplasm/metabolism/genetics ; },
abstract = {TDP-43 is a normally nuclear RNA binding protein that under pathological conditions may be excluded from the nucleus and deposited in the cytoplasm in the form of insoluble polyubiquitinated and polyphosphorylated inclusions. This nuclear exclusion coupled with cytoplasmic accumulation is called TDP-43 pathology and contributes to a range of disorders collectively known as TDP-43 proteinopathies. These include the great majority of amyotrophic lateral sclerosis (ALS) cases, all limbic-predominant age-related TDP-43 encephalopathy (LATE), as well as up to 50% of frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) cases. Thus, TDP-43 pathology is a common feature underlying a wide range of neurodegenerative conditions. However, modelling it has proven to be challenging, particularly generating models with concomitant TDP-43 loss of nuclear function and cytoplasmic inclusions. Here, focussing exclusively on mice, we discuss TDP-43 genetic models in terms of the presence of TDP-43 pathology, and we consider other models with TDP-43 pathology due to mutations in disparate genes. We also consider manipulations aimed at producing TDP-43 pathology, and we look at potential strategies to develop new, much needed models to address the many outstanding questions regarding how and why TDP-43 protein leaves the nucleus and accumulates in the cytoplasm, causing downstream dysfunction and devastating disease.},
}

Animals
*DNA-Binding Proteins/genetics/metabolism
Mice
*Disease Models, Animal
*TDP-43 Proteinopathies/genetics/pathology/metabolism
Humans
Mutation
Amyotrophic Lateral Sclerosis/genetics/pathology
Cell Nucleus/genetics/metabolism
Cytoplasm/metabolism/genetics

@article {pmid40302786,
year = {2025},
author = {Vijayaraghavan, M and Murali, SP and Thakur, G and Li, XJ},
title = {Role of glial cells in motor neuron degeneration in hereditary spastic paraplegias.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1553658},
pmid = {40302786},
issn = {1662-5102},
support = {R01 NS118066/NS/NINDS NIH HHS/United States ; },
abstract = {This review provides a comprehensive overview of hereditary spastic paraplegias (HSPs) and summarizes the recent progress on the role of glial cells in the pathogenesis of HSPs. HSPs are a heterogeneous group of neurogenetic diseases characterized by axonal degeneration of cortical motor neurons, leading to muscle weakness and atrophy. Though the contribution of glial cells, especially astrocytes, to the progression of other motor neuron diseases like amyotrophic lateral sclerosis (ALS) is well documented, the role of glial cells and the interaction between neurons and astrocytes in HSP remained unknown until recently. Using human pluripotent stem cell-based models of HSPs, a study reported impaired lipid metabolisms and reduced size of lipid droplets in HSP astrocytes. Moreover, targeting lipid dysfunction in astrocytes rescues axonal degeneration of HSP cortical neurons, demonstrating a non-cell-autonomous mechanism in axonal deficits of HSP neurons. In addition to astrocytes, recent studies revealed dysfunctions in HSP patient pluripotent stem cell-derived microglial cells. Increased microgliosis and pro-inflammation factors were also observed in HSP patients' samples, pointing to an exciting role of innate immunity and microglia in HSP. Building upon these recent studies, further investigation of the detailed molecular mechanism and the interplay between glial cell dysfunction and neuronal degeneration in HSP by combining human stem cell models, animal models, and patient samples will open avenues for identifying new therapeutic targets and strategies for HSP.},
}

@article {pmid40304712,
year = {2025},
author = {Freisem, D and Hoenigsperger, H and Catanese, A and Sparrer, KMJ},
title = {Inborn errors of canonical autophagy in neurodegenerative diseases.},
journal = {Human molecular genetics},
volume = {34},
number = {R1},
pages = {R23-R34},
pmid = {40304712},
issn = {1460-2083},
support = {CA 2915/4-1//German Research Foundation/ ; CRC1506//German Research Foundation/ ; CRC1279//German Research Foundation/ ; SP 1600/7-1//German Research Foundation/ ; SP 1600/9-1//German Research Foundation/ ; },
mesh = {Humans ; *Autophagy/genetics ; *Neurodegenerative Diseases/genetics/pathology/metabolism ; Animals ; Mitophagy/genetics ; Parkinson Disease/genetics/pathology ; Mutation ; Proteostasis/genetics ; Amyotrophic Lateral Sclerosis/genetics/pathology ; },
abstract = {Neurodegenerative disorders (NDDs), characterized by a progressive loss of neurons and cognitive function, are a severe burden to human health and mental fitness worldwide. A hallmark of NDDs such as Alzheimer's disease, Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and prion diseases is disturbed cellular proteostasis, resulting in pathogenic deposition of aggregated protein species. Autophagy is a major cellular process maintaining proteostasis and integral to innate immune defenses that mediates lysosomal protein turnover. Defects in autophagy are thus frequently associated with NDDs. In this review, we discuss the interplay between NDDs associated proteins and autophagy and provide an overview over recent discoveries in inborn errors in canonical autophagy proteins that are associated with NDDs. While mutations in autophagy receptors seems to be associated mainly with the development of ALS, errors in mitophagy are mainly found to promote PD. Finally, we argue whether autophagy may impact progress and onset of the disease, as well as the potential of targeting autophagy as a therapeutic approach. Concludingly, understanding disorders due to inborn errors in autophagy-"autophagopathies"-will help to unravel underlying NDD pathomechanisms and provide unique insights into the neuroprotective role of autophagy, thus potentially paving the way for novel therapeutic interventions.},
}

Humans
*Autophagy/genetics
*Neurodegenerative Diseases/genetics/pathology/metabolism
Animals
Mitophagy/genetics
Parkinson Disease/genetics/pathology
Mutation
Proteostasis/genetics
Amyotrophic Lateral Sclerosis/genetics/pathology

@article {pmid40305176,
year = {2025},
author = {Erichsen, PA and Henriksen, EE and Nielsen, JE and Ejlerskov, P and Simonsen, AH and Toft, A},
title = {Immunological Fluid Biomarkers in Frontotemporal Dementia: A Systematic Review.},
journal = {Biomolecules},
volume = {15},
number = {4},
pages = {},
pmid = {40305176},
issn = {2218-273X},
support = {0084960//Novo Nordisk Foundation/ ; R450-2023-989//Lundbeck Foundation/ ; },
mesh = {Humans ; *Frontotemporal Dementia/immunology/blood/cerebrospinal fluid ; *Biomarkers/cerebrospinal fluid/blood ; Alzheimer Disease/immunology/blood/cerebrospinal fluid ; Amyotrophic Lateral Sclerosis/blood/immunology/cerebrospinal fluid ; Chitinase-3-Like Protein 1/cerebrospinal fluid/blood ; Glial Fibrillary Acidic Protein/cerebrospinal fluid/blood ; Chemokine CCL2/cerebrospinal fluid/blood ; },
abstract = {Dysregulated immune activation plays a key role in the pathogenesis of neurodegenerative diseases, including frontotemporal dementia (FTD). This study reviews immunological biomarkers associated with FTD and its subtypes. A systematic search of PubMed and Web of Science was conducted for studies published before 1 January 2025, focusing on immunological biomarkers in CSF or blood from FTD patients with comparisons to healthy or neurological controls. A total of 124 studies were included, involving 6686 FTD patients and 202 immune biomarkers. Key findings include elevated levels of GFAP and MCP1/CCL2 in both CSF and blood and consistently increased CHIT1 and YKL-40 in CSF. Complement proteins from the classical activation pathway emerged as promising targets. Distinct immune markers were found to differentiate FTD from Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), with GFAP, SPARC, and SPP1 varying between FTD and AD and IL-15, HERV-K, NOD2, and CHIT1 differing between FTD and ALS. A few markers, such as Galectin-3 and PGRN, distinguished FTD subtypes. Enrichment analysis highlighted IL-10 signaling and immune cell chemotaxis as potential pathways for further exploration. This study provides an overview of immunological biomarkers in FTD, emphasizing those most relevant for future research on immune dysregulation in FTD pathogenesis.},
}

Humans
*Frontotemporal Dementia/immunology/blood/cerebrospinal fluid
*Biomarkers/cerebrospinal fluid/blood
Alzheimer Disease/immunology/blood/cerebrospinal fluid
Amyotrophic Lateral Sclerosis/blood/immunology/cerebrospinal fluid
Chitinase-3-Like Protein 1/cerebrospinal fluid/blood
Glial Fibrillary Acidic Protein/cerebrospinal fluid/blood
Chemokine CCL2/cerebrospinal fluid/blood

@article {pmid40309514,
year = {2025},
author = {Li, V and Huang, Y},
title = {Oligonucleotide therapeutics for neurodegenerative diseases.},
journal = {NeuroImmune pharmacology and therapeutics},
volume = {4},
number = {1},
pages = {1-11},
pmid = {40309514},
issn = {2750-6665},
support = {R44 DC018463/DC/NIDCD NIH HHS/United States ; R44 DC018762/DC/NIDCD NIH HHS/United States ; },
abstract = {Recently there has been a surge in interest involving the application of oligonucleotides, including small interfering RNA (siRNA) and antisense oligonucleotides (ASOs), for the treatment of chronic diseases that have few available therapeutic options. This emerging class of drugs primarily operates by selectively suppressing target genes through antisense and/or RNA interference mechanisms. While various commercial medications exist for delivering oligonucleotides to the hepatic tissue, achieving effective delivery to extra hepatic tissues remains a formidable challenge. Here, we review recent advances in oligonucleotide technologies, including nanoparticle delivery, local administration, and 2'-O-hexadecyl (C16)-conjugation that work to extend the applicability of siRNAs and ASOs to nerve tissues. We discuss critical factors pivotal for the successful clinical translations of these modified or engineered oligonucleotides in the context of treating neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis.},
}

@article {pmid40309789,
year = {2025},
author = {Khan, S and Kallis, L and Mee, H and El Hadwe, S and Barone, D and Hutchinson, P and Kolias, A},
title = {Invasive Brain-Computer Interface for Communication: A Scoping Review.},
journal = {Brain sciences},
volume = {15},
number = {4},
pages = {},
pmid = {40309789},
issn = {2076-3425},
abstract = {BACKGROUND: The rapid expansion of the brain-computer interface for patients with neurological deficits has garnered significant interest, and for patients, it provides an additional route where conventional rehabilitation has its limits. This has particularly been the case for patients who lose the ability to communicate. Circumventing neural injuries by recording from the intact cortex and subcortex has the potential to allow patients to communicate and restore self-expression. Discoveries over the last 10-15 years have been possible through advancements in technology, neuroscience, and computing. By examining studies involving intracranial brain-computer interfaces that aim to restore communication, we aimed to explore the advances made and explore where the technology is heading.

METHODS: For this scoping review, we systematically searched PubMed and OVID Embase. After processing the articles, the search yielded 41 articles that we included in this review.

RESULTS: The articles predominantly assessed patients who had either suffered from amyotrophic lateral sclerosis, cervical cord injury, or brainstem stroke, resulting in tetraplegia and, in some cases, difficulty speaking. Of the intracranial implants, ten had ALS, six had brainstem stroke, and thirteen had a spinal cord injury. Stereoelectroencephalography was also used, but the results, whilst promising, are still in their infancy. Studies involving patients who were moving cursors on a screen could improve the speed of movement by optimising the interface and utilising better decoding methods. In recent years, intracortical devices have been successfully used for accurate speech-to-text and speech-to-audio decoding in patients who are unable to speak.

CONCLUSIONS: Here, we summarise the progress made by BCIs used for communication. Speech decoding directly from the cortex can provide a novel therapeutic method to restore full, embodied communication to patients suffering from tetraplegia who otherwise cannot communicate.},
}

@article {pmid40309800,
year = {2025},
author = {Manai, AL and Caria, P and Noli, B and Contini, C and Manconi, B and Etzi, F and Cocco, C},
title = {VGF and Its Derived Peptides in Amyotrophic Lateral Sclerosis.},
journal = {Brain sciences},
volume = {15},
number = {4},
pages = {},
pmid = {40309800},
issn = {2076-3425},
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a progressive degeneration in the neurons of the frontal cortex, spinal cord, and brainstem, altering the correct release of neurotransmitters. The disease affects every muscle in the body and could cause death three to five years after symptoms first occur. There is currently no efficient treatment to stop the disease's progression. The lack of identification of potential therapeutic strategies is a consequence of the delayed diagnosis due to the absence of accurate ALS early biomarkers. Indeed, neurotransmitters altered in ALS are not measurable in body fluids at quantities that allow for testing, making their use as diagnostic tools a challenge. Contrarily, neuroproteins and neuropeptides are chemical messengers produced and released by neurons, and most of them have the potential to enter bodily fluids. To find out new possible ALS biomarkers, the research of neuropeptides and proteins is intensified using mass spectrometry and biochemical-based assays. Neuropeptides derived from the proVGF precursor protein act as signaling molecules within neurons. ProVGF and its derived peptides are expressed in the nervous and endocrine systems but are also widely distributed in body fluids such as blood, urine, and cerebrospinal fluid, making them viable options as disease biomarkers. To highlight the proVGF and its derived peptides' major roles as ALS diagnostic biomarkers, this review provides an overview of the VGF peptide alterations in spinal cord and body fluids and outlines the limitations of the reported investigations.},
}

@article {pmid40314791,
year = {2025},
author = {Iuzzolino, VV and Scaravilli, A and Carignani, G and Senerchia, G and Pontillo, G and Dubbioso, R and Cocozza, S},
title = {Mapping motor and extra-motor gray and white matter changes in ALS: a comprehensive review of MRI insights.},
journal = {Neuroradiology},
volume = {67},
number = {7},
pages = {1683-1696},
pmid = {40314791},
issn = {1432-1920},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology ; *White Matter/diagnostic imaging/pathology ; *Magnetic Resonance Imaging/methods ; *Gray Matter/diagnostic imaging/pathology ; Disease Progression ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor neurons, yet with substantial clinical variability. Furthermore, beyond motor symptoms, ALS patients also show non-motor features, reflecting its classification as a multi-system disorder. The identification of reliable biomarkers is a critical challenge for improving diagnosis, tracking disease progression, and predicting patient outcomes. This review explores macro- and microstructural alterations in ALS, focusing on gray matter (GM) and white matter (WM) as observed through Magnetic Resonance Imaging (MRI). This approach synthesizes not only the expected involvement of motor areas but also highlights emerging evidence that these changes extend to extra-motor areas, such as the frontal and temporal lobes, underscoring the complex pathophysiology of ALS. The review emphasizes the potential of MRI as a non-invasive tool to provide new biomarkers by assessing both GM and WM integrity, a key advancement in ALS research. Additionally, it addresses existing discrepancies in findings and stresses the need for standardized imaging protocols. It also highlights the role of multi-modal MRI approaches in deepening our understanding of ALS pathology, emphasizing the importance of combining structural and diffusion MRI techniques to offer more comprehensive insights into ALS progression, ultimately advancing the potential for personalized treatment strategies and improving patient outcomes.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology
*White Matter/diagnostic imaging/pathology
*Magnetic Resonance Imaging/methods
*Gray Matter/diagnostic imaging/pathology
Disease Progression

@article {pmid40316871,
year = {2025},
author = {Veit, W and Browning, H and Garcia-Pelegrin, E and Davies, JR and DuBois, JG and Clayton, NS},
title = {Dimensions of corvid consciousness.},
journal = {Animal cognition},
volume = {28},
number = {1},
pages = {35},
pmid = {40316871},
issn = {1435-9456},
mesh = {*Consciousness ; Animals ; Animal Welfare ; *Crows ; },
abstract = {Corvids have long been a target of public fascination and of scientific attention, particularly in the study of animal minds. Using Birch et al.'s (2020) 5-dimensional framework for animal consciousness we ask what it is like to be a corvid and propose a speculative but empirically informed answer. We go on to suggest future directions for research on corvid consciousness and how it can inform ethical treatment and animal welfare legislation.},
}

*Consciousness
Animals
Animal Welfare
*Crows

@article {pmid40319325,
year = {2025},
author = {Mehdizadeh, S and Mamaghani, M and Hassanikia, S and Pilehvar, Y and Ertas, YN},
title = {Exosome-powered neuropharmaceutics: unlocking the blood-brain barrier for next-gen therapies.},
journal = {Journal of nanobiotechnology},
volume = {23},
number = {1},
pages = {329},
pmid = {40319325},
issn = {1477-3155},
mesh = {*Exosomes/metabolism/chemistry ; *Blood-Brain Barrier/metabolism/drug effects ; Humans ; Animals ; *Drug Delivery Systems/methods ; *Neuropharmacology/methods ; Drug Carriers/chemistry ; },
abstract = {BACKGROUND: The blood-brain barrier (BBB) presents a formidable challenge in neuropharmacology, limiting the delivery of therapeutic agents to the brain. Exosomes, nature's nanocarriers, have emerged as a promising solution due to their biocompatibility, low immunogenicity, and innate ability to traverse the BBB. A thorough examination of BBB anatomy and physiology reveals the complexities of neurological drug delivery and underscores the limitations of conventional methods.

MAIN BODY: This review explores the potential of exosome-powered neuropharmaceutics, highlighting their structural and functional properties, biogenesis, and mechanisms of release. Their intrinsic advantages in drug delivery, including enhanced stability and efficient cellular uptake, are discussed in detail. Exosomes naturally overcome BBB barriers through specific translocation mechanisms, making them a compelling vehicle for targeted brain therapies. Advances in engineering strategies, such as genetic and biochemical modifications, drug loading techniques, and specificity enhancement, further bolster their therapeutic potential. Exosome-based approaches hold immense promise for treating a spectrum of neurological disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), brain tumors, stroke, and psychiatric conditions.

CONCLUSION: By leveraging their innate properties and engineering innovations, exosomes offer a versatile platform for precision neurotherapeutics. Despite their promise, challenges remain in clinical translation, including large-scale production, standardization, and regulatory considerations. Future research directions in exosome nanobiotechnology aim to refine these therapeutic strategies, unlocking new avenues for treating neurological diseases. This review underscores the transformative impact of exosome-based drug delivery, paving the way for next-generation therapies that can effectively penetrate the BBB and revolutionize neuropharmacology.},
}

*Exosomes/metabolism/chemistry
*Blood-Brain Barrier/metabolism/drug effects
Humans
Animals
*Drug Delivery Systems/methods
*Neuropharmacology/methods
Drug Carriers/chemistry

@article {pmid40320052,
year = {2025},
author = {Nadeem, A and Sharma, P and Gupta, P and Sandeep, P and Sharma, B and Sharma, N and Yadav, M and Dhiman, N},
title = {Exploring Neuregulin3: From physiology to pathology, a novel target for rational drug design.},
journal = {Biochemical pharmacology},
volume = {238},
number = {},
pages = {116964},
doi = {10.1016/j.bcp.2025.116964},
pmid = {40320052},
issn = {1873-2968},
mesh = {Humans ; Animals ; *Drug Design ; *Neuregulins/metabolism/genetics ; Neoplasms/drug therapy/metabolism/pathology ; *Drug Delivery Systems/methods/trends ; },
abstract = {Neuregulin 3 (NRG3) is an epidermal growth factor related protein that binds to and stimulates the Erb-B2 receptor tyrosine kinase 4 (ErbB4). NRG3 is a multifunctional protein with fifteen alternative splicing isoforms categorized into four classes. Numerous physiological processes, such as the formation of cortical plate, cortical patterning, synaptic development, neuronal proliferation, regulation of neurotransmission, control of impulsive behavior, mammary gland morphogenesis, spermatogonial proliferation and cardiac homeostasis are influenced by NRG3. Besides its physiological roles, NRG3 also modulates anxiogenic phenotypes. It is a susceptibility gene for schizophrenia, autism spectrum disorder and Hirschsprung's Disease. Furthermore, anxiety during nicotine withdrawal is dependent on NRG3-ErbB4 signaling. Research on a range of solid carcinomas, such as brain tumors, ovarian cancer, gastrointestinal cancer and breast cancer, has demonstrated NRG3 gene as a therapeutic target. NRG3 also has potential involvement in epilepsy, angular limb malformation in Rambouillet rams, amyotrophic lateral sclerosis and polythelia. Nevertheless, little is known about the molecular characteristics, activities specific to isoforms, and molecular mechanisms of NRG3. Examining its potential involvement in a range of physiological processes and pathological states is a unique area that needs in-depth study and may offer new mechanistic insights and comprehension of these elements. Thus, the purpose of this review is to shed light on the utility of NRG3 as a potential target in various health and disease conditions.},
}

Humans
Animals
*Drug Design
*Neuregulins/metabolism/genetics
Neoplasms/drug therapy/metabolism/pathology
*Drug Delivery Systems/methods/trends

@article {pmid40320859,
year = {2025},
author = {Watanabe, S and Yamanaka, K},
title = {Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in Neurodegenerative Diseases.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {47},
number = {7},
pages = {e70016},
pmid = {40320859},
issn = {1521-1878},
support = {23K06826//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; 19KK0214//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; 22H00467//Ministry of Education, Culture, Sports, Science and Technology, Japan/Japan Society for the Promotion of Science/ ; JP22ek0109426//Japan Agency for Medical Research and Development/ ; JP24wm0425014//Japan Agency for Medical Research and Development/ ; JP24wm0625301//Japan Agency for Medical Research and Development/ ; //Takeda Science Foundation/ ; //Mochida Memorial Foundation for Medical and Pharmaceutical Research/ ; //Kowa Life Science Foundation/ ; //Novartis Foundation/ ; },
mesh = {Humans ; *Mitochondria/metabolism ; *Endoplasmic Reticulum/metabolism ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; *Proteostasis ; Calcium/metabolism ; Autophagy ; Amyotrophic Lateral Sclerosis/metabolism ; Mitochondrial Membranes/metabolism ; Alzheimer Disease/metabolism ; },
abstract = {Recent evidence indicates that the mitochondria-endoplasmic reticulum (ER) contact site is a novel microdomain essential for cellular homeostasis. Various proteins are accumulated at the mitochondria-associated membrane (MAM), an ER subcomponent closely associated with the mitochondria, contributing to Ca[2+] transfer to the mitochondria, lipid synthesis, mitochondrial fission/fusion, and autophagy. These functions are disrupted in the diseases, particularly in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. In this review, we summarize the disruption of protein homeostasis in various neurodegenerative diseases, present recent works on the mechanisms of MAM aberration, including ours mainly focused on ALS, and then discuss challenges and prospects for future MAM-targeted therapies in neurodegenerative diseases.},
}

Humans
*Mitochondria/metabolism
*Endoplasmic Reticulum/metabolism
*Neurodegenerative Diseases/metabolism/pathology
Animals
*Proteostasis
Calcium/metabolism
Autophagy
Amyotrophic Lateral Sclerosis/metabolism
Mitochondrial Membranes/metabolism
Alzheimer Disease/metabolism

@article {pmid40325332,
year = {2025},
author = {Liu, S and Feng, A and Li, Z},
title = {Neuron-Derived Extracellular Vesicles: Emerging Regulators in Central Nervous System Disease Progression.},
journal = {Molecular neurobiology},
volume = {62},
number = {11},
pages = {14585-14612},
pmid = {40325332},
issn = {1559-1182},
mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Disease Progression ; Animals ; *Central Nervous System Diseases/metabolism/pathology ; *Neurons/metabolism/pathology ; Blood-Brain Barrier/metabolism ; Biomarkers/metabolism ; },
abstract = {The diagnosis and exploration of central nervous system (CNS) diseases remain challenging due to the blood-brain barrier (BBB), complex signaling pathways, and heterogeneous clinical manifestations. Neurons, as the core functional units of the CNS, play a pivotal role in CNS disease progression. Extracellular vesicles (EVs), capable of crossing the BBB, facilitate intercellular and cell-extracellular matrix (ECM) communication, making neuron-derived extracellular vesicles (NDEVs) a focal point of research. Recent studies reveal that NDEVs, carrying various bioactive substances, can exert either pathogenic or protective effects in numerous CNS diseases. Additionally, NDEVs show significant potential as biomarkers for CNS diseases. This review summarizes the emerging roles of NDEVs in CNS diseases, including Alzheimer's disease, depression, traumatic brain injury, schizophrenia, ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. It aims to provide a novel perspective on developing therapeutic and diagnostic strategies for CNS diseases through the study of NDEVs.},
}

Humans
*Extracellular Vesicles/metabolism
*Disease Progression
Animals
*Central Nervous System Diseases/metabolism/pathology
*Neurons/metabolism/pathology
Blood-Brain Barrier/metabolism
Biomarkers/metabolism

@article {pmid40328546,
year = {2025},
author = {Kleinerova, J and Tan, EL and Delaney, S and Smyth, M and Bede, P},
title = {Advances and research priorities in the respiratory management of ALS: Historical perspectives and new technologies.},
journal = {Revue neurologique},
volume = {181},
number = {6},
pages = {525-534},
doi = {10.1016/j.neurol.2025.04.008},
pmid = {40328546},
issn = {0035-3787},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications/history ; *Biomedical Research/trends ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Noninvasive Ventilation/methods ; Respiratory Insufficiency/therapy/etiology ; },
abstract = {Respiratory involvement has been identified as a cardinal feature of amyotrophic lateral sclerosis (ALS) since its earliest descriptions in the 19th century. Since these initial reports, considerable research has been undertaken to clarify the pathophysiology and progression rates associated with respiratory compromise and effective management strategies have been developed. Clinical trials routinely incorporate respiratory measures as study end points, non-invasive ventilation is now widely used in the home setting, cough-assist techniques are commonly used, advanced neurophysiology techniques and wearable technologies have been integrated into respiratory monitoring protocols, and palliative guidelines have been developed to effectively manage respiratory distress. Despite the widespread implementation of these interventions, epidemiology studies are inconsistent and some studies suggest that survival in ALS has not improved significantly with the introduction of these measures. The outcomes of diaphragmatic pacing trials have been disappointing, advanced neurophysiology techniques are not routinely utilised, spinal and brainstem imaging are not commonly undertaken and significant geographical differences exist in proceeding to tracheostomy. The worldwide COVID pandemic has given impetus for remote monitoring, connected devices, video-consultations, and timely vaccinations in ALS; lessons that are invaluable long after the pandemic. Respiratory monitoring and management in ALS is a swiftly evolving facet of ALS care with considerable quality of life benefits.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/complications/history
*Biomedical Research/trends
History, 19th Century
History, 20th Century
History, 21st Century
Noninvasive Ventilation/methods
Respiratory Insufficiency/therapy/etiology

@article {pmid40328798,
year = {2025},
author = {Wu, X and Yang, Z and Zou, J and Gao, H and Shao, Z and Li, C and Lei, P},
title = {Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.},
journal = {Signal transduction and targeted therapy},
volume = {10},
number = {1},
pages = {146},
pmid = {40328798},
issn = {2059-3635},
support = {32070961//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/enzymology/genetics/pathology ; *Drug Discovery ; *Protein Kinases/genetics/metabolism ; *Protein Kinase Inhibitors/therapeutic use ; Signal Transduction/drug effects/genetics ; Phosphorylation ; Animals ; },
abstract = {Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's, Huntington's disease, and Amyotrophic Lateral Sclerosis) are major health threats for the aging population and their prevalences continue to rise with the increasing of life expectancy. Although progress has been made, there is still a lack of effective cures to date, and an in-depth understanding of the molecular and cellular mechanisms of these neurodegenerative diseases is imperative for drug development. Protein phosphorylation, regulated by protein kinases and protein phosphatases, participates in most cellular events, whereas aberrant phosphorylation manifests as a main cause of diseases. As evidenced by pharmacological and pathological studies, protein kinases are proven to be promising therapeutic targets for various diseases, such as cancers, central nervous system disorders, and cardiovascular diseases. The mechanisms of protein phosphatases in pathophysiology have been extensively reviewed, but a systematic summary of the role of protein kinases in the nervous system is lacking. Here, we focus on the involvement of protein kinases in neurodegenerative diseases, by summarizing the current knowledge on the major kinases and related regulatory signal transduction pathways implicated in diseases. We further discuss the role and complexity of kinase-kinase networks in the pathogenesis of neurodegenerative diseases, illustrate the advances of clinical applications of protein kinase inhibitors or novel kinase-targeted therapeutic strategies (such as antisense oligonucleotides and gene therapy) for effective prevention and early intervention.},
}

Humans
*Neurodegenerative Diseases/drug therapy/enzymology/genetics/pathology
*Drug Discovery
*Protein Kinases/genetics/metabolism
*Protein Kinase Inhibitors/therapeutic use
Signal Transduction/drug effects/genetics
Phosphorylation
Animals

@article {pmid40332015,
year = {2025},
author = {Duță, C and Dogaru, CB and Muscurel, C and Stoian, I},
title = {Nanozymes: Innovative Therapeutics in the Battle Against Neurodegenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {8},
pages = {},
pmid = {40332015},
issn = {1422-0067},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/metabolism ; Oxidative Stress/drug effects ; Animals ; Antioxidants/therapeutic use/chemistry/pharmacology ; *Nanostructures/chemistry/therapeutic use ; Reactive Oxygen Species/metabolism ; },
abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), represent a significant challenge to global health due to their progressive nature and the absence of curative treatments. These disorders are characterized by oxidative stress, protein misfolding, and neuroinflammation, which collectively contribute to neuronal damage and death. Recent advancements in nanotechnology have introduced nanozymes-engineered nanomaterials that mimic enzyme-like activities-as promising therapeutic agents. This review explores the multifaceted roles of nanozymes in combating oxidative stress and inflammation in neurodegenerative conditions. By harnessing their potent antioxidant properties, nanozymes can effectively scavenge reactive oxygen species (ROS) and restore redox balance, thereby protecting neuronal function. Their ability to modify surface properties enhances targeted delivery and biocompatibility, making them suitable for various biomedical applications. In this review, we highlight recent findings on the design, functionality, and therapeutic potential of nanozymes, emphasizing their dual role in addressing oxidative stress and pathological features such as protein aggregation. This synthesis of current research underscores the innovative potential of nanozymes as a proactive therapeutic strategy to halt disease progression and improve patient outcomes in neurodegenerative disorders.},
}

Humans
*Neurodegenerative Diseases/drug therapy/metabolism
Oxidative Stress/drug effects
Animals
Antioxidants/therapeutic use/chemistry/pharmacology
*Nanostructures/chemistry/therapeutic use
Reactive Oxygen Species/metabolism

@article {pmid40332510,
year = {2025},
author = {Stacchiotti, C and Mazzella di Regnella, S and Cinotti, M and Spalloni, A and Volpe, E},
title = {Neuroinflammation and Amyotrophic Lateral Sclerosis: Recent Advances in Anti-Inflammatory Cytokines as Therapeutic Strategies.},
journal = {International journal of molecular sciences},
volume = {26},
number = {8},
pages = {},
pmid = {40332510},
issn = {1422-0067},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/immunology ; *Cytokines/therapeutic use/metabolism ; Animals ; *Neuroinflammatory Diseases/drug therapy/metabolism/pathology ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Blood-Brain Barrier/metabolism ; Inflammation ; },
abstract = {Neuroinflammation is an inflammatory response occurring within the central nervous system (CNS). The process is marked by the production of pro-inflammatory cytokines, chemokines, small-molecule messengers, and reactive oxygen species. Microglia and astrocytes are primarily involved in this process, while endothelial cells and infiltrating blood cells contribute to neuroinflammation when the blood-brain barrier (BBB) is damaged. Neuroinflammation is increasingly recognized as a pathological hallmark of several neurological diseases, including amyotrophic lateral sclerosis (ALS), and is closely linked to neurodegeneration, another key feature of ALS. In fact, neurodegeneration is a pathological trigger for inflammation, and neuroinflammation, in turn, contributes to motor neuron (MN) degeneration through the induction of synaptic dysfunction, neuronal death, and inhibition of neurogenesis. Importantly, resolution of acute inflammation is crucial for avoiding chronic inflammation and tissue destruction. Inflammatory processes are mediated by soluble factors known as cytokines, which are involved in both promoting and inhibiting inflammation. Cytokines with anti-inflammatory properties may exert protective roles in neuroinflammatory diseases, including ALS. In particular, interleukin (IL)-10, transforming growth factor (TGF)-β, IL-4, IL-13, and IL-9 have been shown to exert an anti-inflammatory role in the CNS. Other recently emerging immune regulatory cytokines in the CNS include IL-35, IL-25, IL-37, and IL-27. This review describes the current understanding of neuroinflammation in ALS and highlights recent advances in the role of anti-inflammatory cytokines within CNS with a particular focus on their potential therapeutic applications in ALS. Furthermore, we discuss current therapeutic strategies aimed at enhancing the anti-inflammatory response to modulate neuroinflammation in this disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology/immunology
*Cytokines/therapeutic use/metabolism
Animals
*Neuroinflammatory Diseases/drug therapy/metabolism/pathology
*Anti-Inflammatory Agents/therapeutic use/pharmacology
Blood-Brain Barrier/metabolism
Inflammation

@article {pmid40333317,
year = {2025},
author = {Simula, ER and Jasemi, S and Cossu, D and Fais, M and Cossu, I and Chessa, V and Canu, M and Sechi, LA},
title = {Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders.},
journal = {Vaccines},
volume = {13},
number = {4},
pages = {},
pmid = {40333317},
issn = {2076-393X},
support = {PNRR-MCNT1-2023-12376993//Ministero della Salute/ ; 2022BP837R//MUR, PRIN 2022/ ; 22//Regione Autonoma Sardegna grant: legge regionale 12 22 December 2022/ ; e.INS Ecosystem of Innovation for Next Generation Sardinia spoke n 5//European Union/ ; },
abstract = {Human Endogenous Retroviruses comprise approximately 8% of the human genome, serving as fragments of ancient retroviral infections. Although they are generally maintained in a silenced state by robust epigenetic mechanisms, specific HERV groups, particularly HERV-W and HERV-K, can become derepressed under specific pathological conditions, thereby contributing to the initiation and progression of neuroinflammatory and neurodegenerative processes. Preclinical studies and clinical trials, such as those investigating monoclonal antibodies, indicate that directly targeting these elements may offer a novel therapeutic strategy. In this review, we provide an overview of HERVs' biology, examine their role in neurodegenerative diseases such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, and Parkinson's disease, and explore their therapeutic prospects, highlighting both the challenges and the potential future research directions needed to translate these approaches into clinical interventions.},
}

@article {pmid40338639,
year = {2025},
author = {Barchiesi, MA and Calabrese, A and Costa, R and Di Pillo, F and D'Uffizi, A and Tiburzi, L and Zahid, E},
title = {Continuous glucose monitoring in type 2 diabetes: a systematic review of barriers and opportunities for care improvement.},
journal = {International journal for quality in health care : journal of the International Society for Quality in Health Care},
volume = {37},
number = {3},
pages = {},
pmid = {40338639},
issn = {1464-3677},
mesh = {Humans ; *Diabetes Mellitus, Type 2/blood ; *Blood Glucose Self-Monitoring/methods/instrumentation ; Blood Glucose/analysis ; Quality Improvement ; Telemedicine ; Continuous Glucose Monitoring ; },
abstract = {BACKGROUND: Diabetes mellitus, particularly type 2 diabetes (T2DM), is a chronic disease associated with serious complications, such as heart disease, kidney failure, and blindness. Continuous glucose monitoring (CGM) systems have emerged as a more effective alternative to traditional fingerstick testing, offering patients greater control over their condition. Despite their potential benefits, several barriers to CGM sensor use persist, limiting their widespread adoption among patients with T2DM. This review explores the barriers to CGM sensor use, particularly from the patient's perspective.

METHODS: A systematic literature review is conducted following PRISMA guidelines. The search focuses on studies published between January 2018 and June 2024 and is performed in two primary databases, PubMed and Scopus, selected for their relevance to T2DM research. Studies are included if they explore challenges and barriers to CGM adoption, report patient perspectives, or provide insights into the usability and accessibility of technology. The data are analyzed using deductive content analysis, applying Wilson et al.'s thematic categories as a predefined framework to systematically classify and interpret barriers to CGM adoption. This approach ensures methodological consistency and alignment with existing research on eHealth adoption challenges.

RESULTS: The review identifies several key barriers to CGM sensor use despite the benefits, such as improved glucose control and reduced hypoglycemic events. Major challenges include the high cost of sensors, wearability issues, discomfort from adhesive materials, and concerns about the visibility of the sensors. Additionally, patients report difficulties in interpreting the large volumes of data generated by CGM systems, as well as discomfort or fear related to sensor insertion. Lack of technological support, low health literacy, and insufficient social support are also identified as factors contributing to non-adoption.

CONCLUSIONS: Policymakers and healthcare providers are encouraged to address these barriers by developing patient-centered strategies that support the adoption of CGM sensors. Successfully overcoming these challenges can further support integrating CGM sensors with the Chronic Care Model and Automated Insulin Delivery systems. As an implication, this integration has the potential to enhance glycemic control and improve patient quality of life in the management of T2DM. Furthermore, addressing these barriers may drive advancements in sensor design, improve accessibility, and minimize the environmental impact of CGM sensor use.},
}

Humans
*Diabetes Mellitus, Type 2/blood
*Blood Glucose Self-Monitoring/methods/instrumentation
Blood Glucose/analysis
Quality Improvement
Telemedicine
Continuous Glucose Monitoring

@article {pmid40340620,
year = {2025},
author = {Shen, D and Liu, A and Yang, X and Liu, Q and Liu, M and Cui, L},
title = {Exploring oculomotor challenges in amyotrophic lateral sclerosis: a comprehensive review.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {26},
number = {5-6},
pages = {478-484},
doi = {10.1080/21678421.2025.2501690},
pmid = {40340620},
issn = {2167-9223},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis ; *Ocular Motility Disorders/etiology/physiopathology/diagnosis ; *Eye Movements/physiology ; Disease Progression ; *Cognitive Dysfunction/physiopathology/etiology ; },
abstract = {Traditionally understood as a motor neuron disease, amyotrophic lateral sclerosis (ALS) is now recognized to involve broader neurodegenerative processes, including the oculomotor system. This narrative review summarizes current evidence on oculomotor dysfunction in ALS, with a focus on its relationship to disease-related motor and cognitive impairments. Specifically, the review examines key eye-tracking (ET) metrics, including saccades, smooth pursuit, and fixation, highlighting their potential to reflect both motor and extramotor degeneration. Notably, patients with bulbar-onset ALS exhibit more pronounced oculomotor impairments. By synthesizing findings on the connection between oculomotor dysfunction and cognitive decline, this review underscores the potential of ET as a noninvasive tool for assessing ALS progression. Oculomotor metrics, as part of a broader understanding of ALS's impact on multiple neural networks, may offer valuable insights to refine patient assessment and care strategies, particularly in advanced disease stages.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/complications/diagnosis
*Ocular Motility Disorders/etiology/physiopathology/diagnosis
*Eye Movements/physiology
Disease Progression
*Cognitive Dysfunction/physiopathology/etiology

@article {pmid40340943,
year = {2025},
author = {Kellett, EA and Bademosi, AT and Walker, AK},
title = {Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration.},
journal = {Molecular neurodegeneration},
volume = {20},
number = {1},
pages = {53},
pmid = {40340943},
issn = {1750-1326},
mesh = {Humans ; *DNA-Binding Proteins/metabolism ; Phosphorylation/physiology ; Animals ; *Neurodegenerative Diseases/metabolism ; Amyotrophic Lateral Sclerosis/metabolism ; },
abstract = {Increased phosphorylation of TDP-43 is a pathological hallmark of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the regulation and roles of TDP-43 phosphorylation remain incompletely understood. A variety of techniques have been utilized to understand TDP-43 phosphorylation, including kinase/phosphatase manipulation, phosphomimic variants, and genetic, physical, or chemical inducement in a variety of cell cultures and animal models, and via analyses of post-mortem human tissues. These studies have produced conflicting results: suggesting incongruously that TDP-43 phosphorylation may either drive disease progression or serve a neuroprotective role. In this review, we explore the roles of regulators of TDP-43 phosphorylation including the putative TDP-43 kinases c-Abl, CDC7, CK1, CK2, IKKβ, p38α/MAPK14, MEK1, TTBK1, and TTBK2, and TDP-43 phosphatases PP1, PP2A, and PP2B, in disease. Building on recent studies, we also examine the consequences of TDP-43 phosphorylation on TDP-43 pathology, especially related to TDP-43 mislocalisation, liquid-liquid phase separation, aggregation, and neurotoxicity. By comparing conflicting findings from various techniques and models, this review highlights both the discrepancies and unresolved aspects in the understanding of TDP-43 phosphorylation. We propose that the role of TDP-43 phosphorylation is site and context dependent, and includes regulation of liquid-liquid phase separation, subcellular mislocalisation, and degradation. We further suggest that greater consideration of the normal functions of the regulators of TDP-43 phosphorylation that may be perturbed in disease is warranted. This synthesis aims to build towards a comprehensive understanding of the complex role of TDP-43 phosphorylation in the pathogenesis of neurodegeneration.},
}

Humans
*DNA-Binding Proteins/metabolism
Phosphorylation/physiology
Animals
*Neurodegenerative Diseases/metabolism
Amyotrophic Lateral Sclerosis/metabolism

@article {pmid40344943,
year = {2025},
author = {Zhou, ZD and Yi, L and Popławska-Domaszewicz, K and Chaudhuri, KR and Jankovic, J and Tan, EK},
title = {Glucagon-like peptide-1 receptor agonists in neurodegenerative diseases: Promises and challenges.},
journal = {Pharmacological research},
volume = {216},
number = {},
pages = {107770},
doi = {10.1016/j.phrs.2025.107770},
pmid = {40344943},
issn = {1096-1186},
mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use ; *Hypoglycemic Agents/therapeutic use ; Glucagon-Like Peptide-1 Receptor/metabolism ; },
abstract = {Glucagon-like peptide-1 (GLP-1) receptor agonists (GRA) belong to a class of compounds that reduce blood glucose and energy intake by simulating actions of endogenous incretin hormone GLP-1 after it is released by the gut following food consumption. They are used to treat type 2 diabetes mellitus (T2DM) and obesity and have systemic effects on various organs, including the brain, liver, pancreas, heart, and the gut. Patients with T2DM have a higher risk of developing neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), accompanied by more severe motor deficits and faster disease progression, suggesting dysregulation of insulin signaling in these diseases. Experimental studies have shown that GRA have protective effects to modulate neuroinflammation, oxidative stress, mitochondrial and autophagic functions, and protein misfolding. Hence the compounds have generated enormous interest as novel therapeutic agents against NDs. To date, clinical trials have shown that three GRA, exenatide, liraglutide and lixisenatide can improve motor deficits as an add-on therapy in PD patients and liraglutide can improve cognitive function in AD patients. The neuroprotective effects of these and other GRA, such as PT320 (a sustained-released exenatide) and semaglutide, are still under investigation. The dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonists have been demonstrated to have beneficial effects in AD and PD mice models. Overall, GRA are highly promising novel drugs, but future clinical studies should identify which subsets of patients should be targeted as potential candidates for their symptomatic and/or neuroprotective benefits, investigate whether combinations with other classes of drugs can further augment their efficacy, and evaluate their long-term disease-modifying and adverse effects.},
}

Humans
*Glucagon-Like Peptide-1 Receptor Agonists
Animals
*Neurodegenerative Diseases/drug therapy/metabolism
*Neuroprotective Agents/therapeutic use
*Hypoglycemic Agents/therapeutic use
Glucagon-Like Peptide-1 Receptor/metabolism

@article {pmid40347374,
year = {2025},
author = {Varshney, V and Gabble, BC and Bishoyi, AK and Varma, P and Qahtan, SA and Kashyap, A and Panigrahi, R and Nathiya, D and Chauhan, AS},
title = {Exploring Exosome-Based Approaches for Early Diagnosis and Treatment of Neurodegenerative Diseases.},
journal = {Molecular neurobiology},
volume = {62},
number = {11},
pages = {14683-14705},
pmid = {40347374},
issn = {1559-1182},
mesh = {Humans ; *Exosomes/metabolism ; *Neurodegenerative Diseases/diagnosis/therapy/metabolism ; Early Diagnosis ; Animals ; Biomarkers/metabolism ; },
abstract = {Neurodegenerative diseases (NDs), like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), present an increasingly significant global health burden, primarily due to the lack of effective early diagnostic tools and treatments. Exosomes-nano-sized extracellular vesicles secreted by nearly all cell types-have emerged as promising candidates for both biomarkers and therapeutic agents in NDs. This review examines the biogenesis, molecular composition, and diverse functions of exosomes in NDs. Exosomes play a crucial role in mediating intercellular communication. They are capable of reflecting the biochemical state of their parent cells and have the ability to cross the blood-brain barrier (BBB). In doing so, they facilitate the propagation of pathological proteins, such as amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn), while also enabling the targeted delivery of neuroprotective compounds. Recent advancements in exosome isolation and engineering have opened up new possibilities for diagnostic and therapeutic strategies. These range from the discovery of non-invasive biomarkers to innovative approaches in gene therapy and drug delivery systems. However, challenges related to standardization, safety, and long-term effects must be addressed before exosomes can be translated into clinical applications. This review highlights both the promising potential and the obstacles that must be overcome to leverage exosomes in the treatment of NDs and the transformation of personalized medicine.},
}

Humans
*Exosomes/metabolism
*Neurodegenerative Diseases/diagnosis/therapy/metabolism
Early Diagnosis
Animals
Biomarkers/metabolism

@article {pmid40350140,
year = {2025},
author = {Amin, MA and Zehravi, M and Sweilam, SH and Shatu, MM and Durgawale, TP and Qureshi, MS and Durgapal, S and Haque, MA and Vodeti, R and Panigrahy, UP and Ahmad, I and Khan, SL and Emran, TB},
title = {Neuroprotective potential of epigallocatechin gallate in Neurodegenerative Diseases: Insights into molecular mechanisms and clinical Relevance.},
journal = {Brain research},
volume = {1860},
number = {},
pages = {149693},
doi = {10.1016/j.brainres.2025.149693},
pmid = {40350140},
issn = {1872-6240},
mesh = {Humans ; *Catechin/analogs & derivatives/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; Oxidative Stress/drug effects ; Clinical Relevance ; },
abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis pose significant challenges due to their complex pathophysiology and lack of effective treatments. Green tea, rich in the epigallocatechin gallate (EGCG) polyphenolic component, has demonstrated potential as a neuroprotective agent with numerous medicinal applications. EGCG effectively reduces tau and Aβ aggregation in ND models, promotes autophagy, and targets key signaling pathways like Nrf2-ARE, NF-κB, and MAPK. This review explores the molecular processes that underlie EGCG's neuroprotective properties, including its ability to regulate mitochondrial dysfunction, oxidative stress, neuroinflammation, and protein misfolding. Clinical research indicates that EGCG may enhance cognitive and motor abilities, potentially inhibiting disease progression despite absorption and dose optimization limitations. The substance has been proven to slow the amyloidogenic process, prevent protein aggregation, decrease amyloid cytotoxicity, inhibit fibrillogenesis, and restructure fibrils for synergistic therapeutic effects. The review highlights the potential of EGCG as a natural, multi-targeted strategy for NDs but emphasizes the need for further clinical trials to enhance its therapeutic efficacy.},
}

Humans
*Catechin/analogs & derivatives/pharmacology/therapeutic use
*Neuroprotective Agents/pharmacology/therapeutic use
*Neurodegenerative Diseases/drug therapy/metabolism
Animals
Oxidative Stress/drug effects
Clinical Relevance

@article {pmid40350633,
year = {2025},
author = {Ishiura, H},
title = {[Genetics of Motor Neuron Diseases and Hereditary Spastic Paraplegia].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {77},
number = {5},
pages = {481-491},
doi = {10.11477/mf.188160960770050481},
pmid = {40350633},
issn = {1881-6096},
mesh = {Humans ; *Spastic Paraplegia, Hereditary/genetics/diagnosis/therapy ; *Motor Neuron Disease/genetics/diagnosis ; },
abstract = {Motor neuron diseases encompass a range of phenotypes, including amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and spinal muscular atrophy (SMA). Related conditions include spinal and bulbar muscular atrophy (SBMA) and hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). Hereditary spastic paraplegia (HSP)-a group of disorders primarily affecting the corticospinal tract-also exhibits diverse clinical manifestations. This review summarizes the genetic basis of these diseases, along with their clinical characteristics, diagnostic approaches, and disease-specific therapies.},
}

Humans
*Spastic Paraplegia, Hereditary/genetics/diagnosis/therapy
*Motor Neuron Disease/genetics/diagnosis

@article {pmid40350723,
year = {2025},
author = {Kuznetsova, DR and Kutlubaev, MA and Pervushina, EV},
title = {[Oculomotor disorders in patients with amyotrophic lateral sclerosis].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {125},
number = {4},
pages = {7-12},
doi = {10.17116/jnevro20251250417},
pmid = {40350723},
issn = {1997-7298},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; *Ocular Motility Disorders/etiology/physiopathology/diagnosis ; Saccades ; Eye Movements ; },
abstract = {Oculomotor disorders are not typical manifestations of amyotrophic lateral sclerosis (ALS). Occasionally, this disease is associated with vertical gaze paresis, presenting a distinct type as «ALS+progressive supranuclear palsy». Studies using eye-tracking methods have revealed a variety of subclinical oculomotor disorders in this disease. These disorders can manifest as changes in reflex and voluntary saccades, antisaccades, smooth tracking eye movements, and fixations. A significant association between oculomotor disorders and clinical manifestations of ALS was reported. The occurrence of oculomotor disorders indicates the involvement of broader neuroanatomical structures, including the prefrontal cortex and basal ganglia. The lack of consistency in the data from different studies and their limited number emphasize the need for further research in this area.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/physiopathology
*Ocular Motility Disorders/etiology/physiopathology/diagnosis
Saccades
Eye Movements

@article {pmid40350993,
year = {2025},
author = {Vedeler, A and Tartaglia, GG and Pastore, A},
title = {Annexin, a Protein for All Seasons: From Calcium Dependent Membrane Metabolism to RNA Recognition.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {47},
number = {7},
pages = {e70019},
pmid = {40350993},
issn = {1521-1878},
support = {ASTRA_855923//ERC / ; PNRRCN00000041andEPNRRCN3//Piano Nazionale di Ripresa e Resilienza of Italian MUR/ ; IVBM4PAP_101098989//EIC Pathfinder/ ; ARUK_PG2019B-020//ARUK / ; },
mesh = {*Annexins/metabolism/chemistry ; Humans ; *Calcium/metabolism ; Animals ; *Cell Membrane/metabolism ; *RNA/metabolism ; *RNA-Binding Proteins/metabolism ; Protein Binding ; },
abstract = {Annexins are a protein family well known to bind to phospholipids in a calcium-dependent way. They are involved in several different crucial cellular processes such as cell division, calcium signaling, membrane repair, vesicle trafficking, and apoptosis. Although RNA binding for some members of the family was reported long ago, it was only recently that it was shown that a common feature of the family is also the ability to bind RNA, a discovery that has added significantly to our perception of the cellular role of these proteins. In the present review, we discuss the properties of annexins under an updated light and the current knowledge on the RNA binding properties of annexins. We then focus specifically on annexin A11, because this is a less characterized member of the family but, at the same time, a potentially important component of the mRNA transport machinery in neurons. We hope to offer to the reader a more complete picture of the annexins' binding properties and new tools to evaluate the multifaceted functions of this important protein family.},
}

*Annexins/metabolism/chemistry
Humans
*Calcium/metabolism
Animals
*Cell Membrane/metabolism
*RNA/metabolism
*RNA-Binding Proteins/metabolism
Protein Binding

@article {pmid40353906,
year = {2025},
author = {Kleinerova, J and Querin, G and Pradat, PF and Siah, WF and Bede, P},
title = {New developments in imaging in ALS.},
journal = {Journal of neurology},
volume = {272},
number = {6},
pages = {392},
pmid = {40353906},
issn = {1432-1459},
support = {JPND-Cofund-2-2019-1/HRBI_/Health Research Board/Ireland ; HRB EIA-2017-019/HRBI_/Health Research Board/Ireland ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology ; *Neuroimaging/methods/trends ; *Brain/diagnostic imaging ; Magnetic Resonance Imaging ; },
abstract = {Neuroimaging in ALS has contributed considerable academic insights in recent years demonstrating genotype-specific topological changes decades before phenoconversion and characterising longitudinal propagation patterns in specific phenotypes. It has elucidated the radiological underpinnings of specific clinical phenomena such as pseudobulbar affect, apathy, behavioural change, spasticity, and language deficits. Academic concepts such as sexual dimorphism, motor reserve, cognitive reserve, adaptive changes, connectivity-based propagation, pathological stages, and compensatory mechanisms have also been evaluated by imaging. The underpinnings of extra-motor manifestations such as cerebellar, sensory, extrapyramidal and cognitive symptoms have been studied by purpose-designed imaging protocols. Clustering approaches have been implemented to uncover radiologically distinct disease subtypes and machine-learning models have been piloted to accurately classify individual patients into relevant diagnostic, phenotypic, and prognostic categories. Prediction models have been developed for survival in symptomatic patients and phenoconversion in asymptomatic mutation carriers. A range of novel imaging modalities have been implemented and 7 Tesla MRI platforms are increasingly being used in ALS studies. Non-ALS MND conditions, such as PLS, SBMA, and SMA, are now also being increasingly studied by quantitative neuroimaging approaches. A unifying theme of recent imaging papers is the departure from describing focal brain changes to focusing on dynamic structural and functional connectivity alterations. Progressive cortico-cortical, cortico-basal, cortico-cerebellar, cortico-bulbar, and cortico-spinal disconnection has been consistently demonstrated by recent studies and recognised as the primary driver of clinical decline. These studies have led the reconceptualisation of ALS as a "network" or "circuitry disease".},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnostic imaging/physiopathology/pathology
*Neuroimaging/methods/trends
*Brain/diagnostic imaging
Magnetic Resonance Imaging

@article {pmid40355001,
year = {2025},
author = {Ognard, J and El Hajj, G and Verma, O and Ghozy, S and Kadirvel, R and Kallmes, DF and Brinjikji, W},
title = {Advances in endovascular brain computer interface: Systematic review and future implications.},
journal = {Journal of neuroscience methods},
volume = {420},
number = {},
pages = {110471},
doi = {10.1016/j.jneumeth.2025.110471},
pmid = {40355001},
issn = {1872-678X},
mesh = {*Brain-Computer Interfaces/trends ; Animals ; Humans ; *Endovascular Procedures/methods/trends ; *Brain/physiology ; Electrodes, Implanted ; },
abstract = {BACKGROUND: Brain-computer interfaces (BCIs) translate neural activity into real-world commands. While traditional invasive BCIs necessitate craniotomy, endovascular BCIs offer a minimally invasive alternative using the venous system for electrode placement.

NEW METHOD: This systematic review evaluates the technical feasibility, safety, and clinical outcomes of endovascular BCIs, discussing their future implications. A systematic review was conducted per PRISMA guidelines. The search spanned PubMed, Web of Science, and Scopus databases using keywords related to neural interfaces and endovascular approaches. Studies were included if they reported on endovascular BCIs in preclinical or clinical settings. Dual independent screening and extraction focused on electrode material, recording capabilities, safety parameters, and clinical efficacy.

RESULTS: From 1385 initial publications, 26 met the inclusion criteria. Seventeen studies investigated the Stentrode device. Among the 24 preclinical studies, 16 used ovine or rodent models, and 9 addressed engineering or simulation aspects. Two clinical studies reported six ALS patients successfully using an endovascular BCI for digital communication. Preclinical data established the endovascular ovine model, demonstrating stable neural recordings and vascular changes with long-term implantation. Key challenges include thrombosis risk, long-term electrode stability, and anatomical variability.

Endovascular BCI reduced invasiveness, improved safety profiles, with comparable neural recording fidelity to invasive methods, and promising preliminary clinical outcomes in severely paralyzed patients.

CONCLUSIONS: Early results are promising, but clinical data remain scarce. Further research is needed to optimize signal processing, enhance electrode biocompatibility, and refine endovascular procedures for broader clinical applications.},
}

*Brain-Computer Interfaces/trends
Animals
Humans
*Endovascular Procedures/methods/trends
*Brain/physiology
Electrodes, Implanted

@article {pmid40360341,
year = {2025},
author = {Lin, W and Huang, C and Tan, Z and Xu, H and Wei, W and Wang, L},
title = {Cu[II]-bis(thioureido) Complex: A Potential Radiotracer for Detecting Oxidative Stress and Neuroinflammation in Neurodegenerative Diseases.},
journal = {Seminars in nuclear medicine},
volume = {55},
number = {4},
pages = {577-586},
doi = {10.1053/j.semnuclmed.2025.03.008},
pmid = {40360341},
issn = {1558-4623},
mesh = {Humans ; *Oxidative Stress ; *Neurodegenerative Diseases/diagnostic imaging/metabolism/complications ; Animals ; *Copper/chemistry ; *Neuroinflammatory Diseases/diagnostic imaging/metabolism/complications ; Positron-Emission Tomography ; Radioactive Tracers ; *Thiosemicarbazones/chemistry ; },
abstract = {Neurodegenerative diseases, characterized by progressive neuronal degeneration and associated with neuroinflammation and oxidative stress, present significant challenges in diagnosis and treatment. This review explores the potential of copper(II)-bis(thiosemicarbazone) complexes, particularly Cu-ATSM, as a dual-purpose radiopharmaceutical for imaging and therapeutic interventions. Cu-ATSM exhibits unique redox-dependent retention in pathological microenvironments, driven by mitochondrial dysfunction and hyper-reductive states, which enables the noninvasive detection of oxidative stress via positron emission tomography (PET). Preclinical studies demonstrate its efficacy in mitigating neuroinflammation by suppressing glial activation, reducing the secretion of pro-inflammatory cytokines (e.g., TNF-α, MCP-1), and increasing the expression of neuroprotective metallothionein-1 (MT1). Some Clinical research reveals elevated [64]Cu-ATSM uptake in Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) patients, correlating with disease severity and regional oxidative stress markers. Furthermore, Cu-ATSM derivatives show promise in modulating blood-brain barrier (BBB) permeability, enhancing amyloid-β clearance, and restoring copper homeostasis in ALS models. Despite these advances, limitations such as small cohort sizes and heterogeneity in clinical studies underscore the need for larger-scale validation. Multimodal imaging integrating PET and MRI, alongside novel structural analogs targeting Aβ plaques and redox imbalances, emerges as a strategic direction for future research. Collectively, Cu-ATSM represents a transformative tool for elucidating neuropathological mechanisms and advancing therapeutic strategies in neurodegenerative disorders.},
}

Humans
*Oxidative Stress
*Neurodegenerative Diseases/diagnostic imaging/metabolism/complications
Animals
*Copper/chemistry
*Neuroinflammatory Diseases/diagnostic imaging/metabolism/complications
Positron-Emission Tomography
Radioactive Tracers
*Thiosemicarbazones/chemistry

@article {pmid40362304,
year = {2025},
author = {Shiryaeva, O and Tolochko, C and Alekseeva, T and Dyachuk, V},
title = {Targets and Gene Therapy of ALS (Part 1).},
journal = {International journal of molecular sciences},
volume = {26},
number = {9},
pages = {},
pmid = {40362304},
issn = {1422-0067},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/genetics/pathology ; *Genetic Therapy/methods ; Animals ; Superoxide Dismutase-1/genetics ; C9orf72 Protein/genetics ; Mutation ; Gene Editing ; RNA-Binding Protein FUS/genetics ; Oligonucleotides, Antisense/therapeutic use ; CRISPR-Cas Systems ; DNA-Binding Proteins/genetics ; RNA Interference ; MicroRNAs/genetics ; Disease Models, Animal ; RNA, Small Interfering/genetics ; Motor Neurons/metabolism/pathology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons, which causes muscle atrophy. Genetic forms of ALS are recorded only in 10% of cases. However, over the past decade, studies in genetics have substantially contributed to our understanding of the molecular mechanisms underlying ALS. The identification of key mutations such as SOD1, C9orf72, FUS, and TARDBP has led to the development of targeted therapy that is gradually being introduced into clinical trials, opening up a broad range of opportunities for correcting these mutations. In this review, we aimed to present an extensive overview of the currently known mechanisms of motor neuron degeneration associated with mutations in these genes and also the gene therapy methods for inhibiting the expression of their mutant proteins. Among these, antisense oligonucleotides, RNA interference (siRNA and miRNA), and gene-editing (CRISPR/Cas9) methods are of particular interest. Each has shown its efficacy in animal models when targeting mutant genes, whereas some of them have proven to be efficient in human clinical trials.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/genetics/pathology
*Genetic Therapy/methods
Animals
Superoxide Dismutase-1/genetics
C9orf72 Protein/genetics
Mutation
Gene Editing
RNA-Binding Protein FUS/genetics
Oligonucleotides, Antisense/therapeutic use
CRISPR-Cas Systems
DNA-Binding Proteins/genetics
RNA Interference
MicroRNAs/genetics
Disease Models, Animal
RNA, Small Interfering/genetics
Motor Neurons/metabolism/pathology

@article {pmid40362512,
year = {2025},
author = {Chong, ZZ and Souayah, N},
title = {Targeting Gene C9orf72 Pathogenesis for Amyotrophic Lateral Sclerosis.},
journal = {International journal of molecular sciences},
volume = {26},
number = {9},
pages = {},
pmid = {40362512},
issn = {1422-0067},
mesh = {*C9orf72 Protein/genetics/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy ; Humans ; DNA Repeat Expansion ; Animals ; Mutation ; Autophagy ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal adult neurodegenerative disorder. Since no cure has been found, finding effective therapeutic targets for ALS remains a major challenge. Gene C9orf72 mutations with the formation of hexanucleotide repeat (GGGGCC) expansion (HRE) have been considered the most common genetic pathogenesis of ALS. The literature review indicates that the C9orf72 HRE causes both the gain-of-function toxicity and loss of function of C9ORF72. The formation of RNA foci and dipeptide repeats (DPRs) resulting from HRE is responsible for toxic function gain. The RNA foci can interfere with RNA processing, while DPRs directly bind to and sequester associated proteins to disrupt processes of rRNA synthesis, mRNA translation, autophagy, and nucleocytoplasmic transport. The mutations of C9orf72 and HRE result in the loss of functional C9ORF72. Under physiological conditions, C9ORF72 binds to Smith-Magenis chromosome region 8 and WD repeat-containing protein and forms a protein complex. Loss of C9ORF72 leads to autophagic impairment, increased oxidative stress, nucleocytoplasmic transport impairment, and inflammatory response. The attempted treatments for ALS have been tried by targeting C9orf72 HRE; however, the outcomes are far from satisfactory yet. More studies should be performed on pharmacological and molecular modulators against C9orf72 HRE to evaluate their efficacy by targeting HRE.},
}

*C9orf72 Protein/genetics/metabolism
*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism/therapy
Humans
DNA Repeat Expansion
Animals
Mutation
Autophagy

@article {pmid40362582,
year = {2025},
author = {Kitaoka, Y and Uchihashi, T and Kawata, S and Nishiura, A and Yamamoto, T and Hiraoka, SI and Yokota, Y and Isomura, ET and Kogo, M and Tanaka, S and Spigelman, I and Seki, S},
title = {Role and Potential of Artificial Intelligence in Biomarker Discovery and Development of Treatment Strategies for Amyotrophic Lateral Sclerosis.},
journal = {International journal of molecular sciences},
volume = {26},
number = {9},
pages = {},
pmid = {40362582},
issn = {1422-0067},
support = {24K13154//Japan Society for the Promotion of Science/ ; 21K10091//Japan Society for the Promotion of Science/ ; 24K13113//Japan Society for the Promotion of Science/ ; 23K09351//Japan Society for the Promotion of Science/ ; 24K13112//Japan Society for the Promotion of Science/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/therapy/diagnosis/metabolism ; Humans ; *Biomarkers/metabolism ; *Artificial Intelligence ; Proteomics/methods ; Neuroimaging/methods ; Deep Learning ; },
abstract = {Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), present significant challenges owing to their complex pathologies and a lack of curative treatments. Early detection and reliable biomarkers are critical but remain elusive. Artificial intelligence (AI) has emerged as a transformative tool, enabling advancements in biomarker discovery, diagnostic accuracy, and therapeutic development. From optimizing clinical-trial designs to leveraging omics and neuroimaging data, AI facilitates understanding of disease and treatment innovation. Notably, technologies such as AlphaFold and deep learning models have revolutionized proteomics and neuroimaging, offering unprecedented insights into ALS pathophysiology. This review highlights the intersection of AI and ALS, exploring the current state of progress and future therapeutic prospects.},
}

*Amyotrophic Lateral Sclerosis/therapy/diagnosis/metabolism
Humans
*Biomarkers/metabolism
*Artificial Intelligence
Proteomics/methods
Neuroimaging/methods
Deep Learning

@article {pmid40364088,
year = {2025},
author = {Plotti, F and Martinelli, A and Terranova, C and De Cicco Nardone, C and Montera, R and Luvero, D and Guzzo, F and Di Donato, V and Cundari, GB and Manco, S and Angioli, R},
title = {Laparoscopic Lateral Suspension (LLS) for Pelvic Organ Prolapse (POP): Update and Systematic Review of Prospective and Randomised Trials.},
journal = {Journal of clinical medicine},
volume = {14},
number = {9},
pages = {},
pmid = {40364088},
issn = {2077-0383},
abstract = {Background: Pelvic organ prolapse (POP) significantly impacts women's quality of life, especially in postmenopausal patients. Although laparoscopic sacrocolpopexy (LSC) is the gold standard for advanced apical prolapse, its complexity and risk of complications have led to alternative approaches like laparoscopic lateral suspension (LLS), a minimally invasive technique with promising results. Methods: A comprehensive search using PubMed databases was performed. The search was conducted from June 2024 to September 2024. The search string used was as follows: (pelvic organ prolapse) AND (lateral suspension) OR (laparoscopic lateral suspension). We included randomized controlled trials, prospective cohort studies, prospective observational studies, and case studies. We excluded retrospective studies, small case series, case reports, and articles not published in English. All selected articles were screened based on the titles and abstracts. Relevant data were extracted and tabulated. Results: An overall number of 12 studies were included in our analysis. LLS demonstrated high anatomical success rates: 91.15% for the anterior, 94.95% for the central, and 86.55% for the posterior compartments. The randomized controlled studies exhibit comparable effectiveness between both methods (LLS vs. LSC) and LLS appears to be the best option for anterior repair or anterior-apical repair. Patient satisfaction rates exceeded 90%, with reduced operative times (123 ± 33 min and 193 ± 55.6 min for ALS and ASC, respectively). According to the Claiven-Dindo scale, 0.17% of postoperative complications were graded more than III. The rate of mesh erosion was 0% to 10%. The technique showed particular benefit for uterine preservation and in obese patients but was less effective for severe posterior prolapse. Conclusions: Laparoscopic lateral suspension offers a safe, effective alternative for POP management, with significant anatomical and functional benefits. Its minimally invasive nature, shorter surgery time, and high satisfaction rates make it suitable for tailored patient care. Further studies should standardize evaluation metrics and assess long-term outcomes. The review was not registered. No funding was received. The authors declare no competing interests.},
}

@article {pmid40371978,
year = {2025},
author = {Shafran, R and Egan, SJ},
title = {Widening the Reach: The Broad Impact of Unguided Self-Help for Eating Disorders.},
journal = {The International journal of eating disorders},
volume = {58},
number = {8},
pages = {1432-1435},
pmid = {40371978},
issn = {1098-108X},
mesh = {Humans ; *Feeding and Eating Disorders/therapy/psychology/prevention & control ; *Cognitive Behavioral Therapy/methods ; *Self Care ; Self Concept ; },
abstract = {A systematic review and meta-analysis conducted by Linardon and colleagues on 27 controlled trials using pure self-help for the prevention and treatment of eating disorders, reported small benefits for co-occurring difficulties such as anxiety, depression, distress and self-esteem. The findings were strongest for pre-selected samples considered at risk or who were symptomatic, and are consistent with literature from other areas indicating that focused interventions have a positive impact on comorbid difficulties. The meta-analysis raises questions about the optimal approach to address comorbidity both within and beyond pure self-help. Understanding the wider impact of disorder-specific approaches compared to transdiagnostic approaches is critical to helping clinicians determine what interventions to use and when. It is notable that CBT interventions across disorders often share treatment techniques and methods to optimize the generalization of learning across difficulties, but such common elements are rarely made explicit. The value of session-by-session measurement as an essential tool to guide clinical decision-making in the context of comorbid difficulties is emphasized. Whilst further work is needed, particularly in clinical samples, the message from Linardon et al.'s meta-analysis is straightforward-pure self-help for the prevention and treatment of eating disorders can have a broad impact in improving mental health.},
}

Humans
*Feeding and Eating Disorders/therapy/psychology/prevention & control
*Cognitive Behavioral Therapy/methods
*Self Care
Self Concept

@article {pmid40374790,
year = {2025},
author = {Verma, KK and Gaur, PK and Gupta, SL and Lata, K and Kaushik, R and Sharma, V},
title = {Metabolomics: a new frontier in neurodegenerative disease biomarker discovery.},
journal = {Metabolomics : Official journal of the Metabolomic Society},
volume = {21},
number = {3},
pages = {67},
pmid = {40374790},
issn = {1573-3890},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism/diagnosis ; *Biomarkers/metabolism/analysis ; *Metabolomics/methods ; Animals ; },
abstract = {BACKGROUND: Neurodegenerative disorders are a group of debilitating diseases affecting the central nervous system, and are characterized by the progressive loss of neurons, leading to declines in cognitive function, movement, and overall quality of life. While the exact causes remain elusive, it's believed that a combination of genetic, environmental, and lifestyle factors contribute to their development. Metabolites, the end products of cellular processes, reflect the physiological state of an organism. By analysing these molecules, researchers can gain a deeper understanding of the underlying metabolic changes associated with neurodegenerative disorders.

AIM OF REVIEW: This review aims to explore the possibilities between metabolites and their association with neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS) and Huntington's disease (HD).

Metabolomic studies could potentially illuminate altered biochemical pathways, facilitating earlier detection and treatment of these conditions. Metabolomic investigations have revealed the role of oxidative stress, alterations in glucose and fat metabolism, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and alterations in myelin composition in neurodegenerative disorders. The common metabolic biomarkers identified includes glutamate, taurine, uric acid, branched chain amino acids, acylcarnitine, creatinine, choline, with some more amino acids and lipids. Metabolomics offers valuable insights into disease mechanisms and potential therapeutic targets by identifying biochemical and metabolic alterations, but still there are several aspects to be explored for accurate mapping of metabolites with specific pathway involved in the disease.},
}

Humans
*Neurodegenerative Diseases/metabolism/diagnosis
*Biomarkers/metabolism/analysis
*Metabolomics/methods
Animals