@article {pmid41345582,
year = {2025},
author = {Ebrahimian, A and Moradi, A and Athari, SZ and Farajdokht, F},
title = {Restless legs syndrome as a comorbidity in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-025-04543-4},
pmid = {41345582},
issn = {1471-2377},
support = {74962//Student Research Committee, Tabriz University of Medical Sciences/ ; },
abstract = {BACKGROUND: Restless Legs Syndrome (RLS), characterized by an urge to move the legs, is linked to neurodegenerative diseases. Emerging evidence suggests a higher RLS prevalence in Amyotrophic Lateral Sclerosis (ALS), impacting quality of life. However, there is lack of comprehensive review addressing its prevalence and associated risk factors. This meta-analysis estimates RLS prevalence in ALS patients compared to healthy controls.

METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies assessing RLS in ALS patients versus controls, adhering to PRISMA guidelines. Two reviewers independently extracted data and assessed bias using Joanna Briggs Institute (JBI) checklist. Meta-analysis used Comprehensive Meta-Analysis software with a random-effects model due to heterogeneity. The certainty of evidence was appraised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.

RESULTS: Out of 291 studies, eight studies (792 ALS, 716 controls) were included. The pooled RLS prevalence in ALS was 17% (95% CI: 14.0%-21.1%; I²: 56.5%; p-value < 0.001). The fixed effect meta-analysis of four studies indicated that the difference of RLS prevalence was statically significant between patients with ALS and healthy controls (OR: 5.65; CI: 2.86-11.13; P-value < 0.001; I²: 28.7.).

CONCLUSION: RLS is significantly more prevalent in ALS patients, potentially worsening sleep and quality of life, mental health, and social well-being. Therefore, it is essential to draw clinicians' attention to RLS in ALS patients due to its potential impact on overall health.},
}

@article {pmid41345047,
year = {2025},
author = {Bahbah, EI},
title = {Tetramethylpyrazine nitrone: a multifaceted neuroprotective agent in neurodegenerative disorders.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/17582024.2025.2598227},
pmid = {41345047},
issn = {1758-2032},
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) share key pathological features, including oxidative stress, mitochondrial dysfunction, and impaired protein homeostasis, yet remain without effective disease-modifying therapies. Tetramethylpyrazine nitrone (TBN), a synthetic derivative of tetramethylpyrazine bearing a free radical-scavenging nitrone moiety, has emerged as a promising multi-target neuroprotective agent. This review synthesizes preclinical and clinical data supporting TBN's therapeutic potential in AD, PD, and ALS. In AD models, TBN reduces amyloid-β accumulation and tau hyperphosphorylation, enhances autophagic clearance, preserves synaptic integrity, and improves cognitive performance. In PD models, TBN confers dopaminergic neuroprotection, restores motor function, and promotes α-synuclein degradation, effects mediated largely through activation of the PGC-1α/Nrf2 pathway and augmentation of the ubiquitin-proteasome system (UPS). In ALS models, TBN mitigates motor neuron loss, improves motor performance, and extends survival, likely via the PGC-1α/Nrf2/HO-1 axis and enhanced autophagic activity. Phase I studies have established TBN's favorable oral and intravenous pharmacokinetics, effective blood - brain barrier penetration, and overall safety and tolerability in healthy volunteers. Owing to its multi-pathway mechanism, principally engaging antioxidant/mitochondrial pathways and proteostasis (autophagy/UPS), TBN represents a compelling candidate for continued clinical development, either as monotherapy or in combination with disease-specific interventions.},
}

@article {pmid41175990,
year = {2025},
author = {Konopka, A},
title = {Perspectives on the utilization of cell-free DNA in amyotrophic lateral sclerosis (ALS) diagnostics and prognostics - insight from cancer research.},
journal = {Neurobiology of disease},
volume = {217},
number = {},
pages = {107167},
doi = {10.1016/j.nbd.2025.107167},
pmid = {41175990},
issn = {1095-953X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/blood ; *Cell-Free Nucleic Acids/blood ; Prognosis ; Biomarkers/blood ; },
abstract = {Amyotrophic lateral sclerosis (ALS) remains a devastating neurodegenerative disease with limited diagnostic and prognostic tools. In recent years, cell-free DNA (cfDNA) has emerged as a promising non-invasive biomarker in various clinical settings, particularly in oncology. Despite its potential, the application of cfDNA in ALS is still in its early stages, and several critical gaps must be addressed. This discussion article reviews the current knowledge about cfDNA in ALS and explores its potential applications for disease diagnosis, monitoring, and prognosis. Drawing on the advances made in cancer research, it also examines the challenges that ALS research may face in cfDNA utilization, highlighting lessons learned from oncology. Taken together, these insights point to the urgent need for a comprehensive understanding of cfDNA characteristics specific to ALS. Given the current lack of reliable diagnostic and prognostic biomarkers in ALS, further investigation into cfDNA represents a valuable and necessary scientific endeavor with the potential to transform patient care and disease management.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/genetics/blood
*Cell-Free Nucleic Acids/blood
Prognosis
Biomarkers/blood

@article {pmid41341655,
year = {2025},
author = {Almalki, S and Salama, M and Taylor, MJ and Ahmed, Z and Tuxworth, RI},
title = {C9orf72-related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review.},
journal = {Frontiers in molecular neuroscience},
volume = {18},
number = {},
pages = {1671906},
pmid = {41341655},
issn = {1662-5099},
abstract = {The G4C2 repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While healthy individuals have fewer than 30 repeats, affected patients may carry hundreds to thousands. This expansion accounts for approximately 40% of familial ALS and 25% of familial FTD cases, and between 5 and 10% cases of sporadic ALS and FTD. Three overlapping pathological mechanisms have been proposed for the C9orf72 expansion: loss of function due to protein deficiency, gain of function through RNA foci, and the production of toxic dipeptide repeat proteins (DPRs) via repeat-associated non-ATG (RAN) translation. This systematic review investigates the role of DNA damage in C9orf72-related ALS-FTD. Analysis of twelve peer-reviewed studies showed that C9orf72 repeat expansions and DPRs compromise genome stability across four experimental models: human cell lines, induced pluripotent stem cell-derived neurons, rodent neurons, and postmortem tissue. We identified four mechanisms underlying DNA damage accumulation: disruption of the ATM pathway, impairment of DNA repair efficiency, formation of R-loops, and mitochondrial dysfunction with oxidative stress. In addition, several consequences of DNA damage were identified, including misrepair-mediated repeat expansion and activation of STING pathway. These findings highlight the key role of DNA damage in C9orf72-related pathology. Consistent with this, targeting DNA damage response factors extended lifespan and improved motor function in mouse models. This review highlights the contribution of DNA damage to C9orf72 pathology and suggest new therapeutic avenues, including personalized approaches based on genetic background.},
}

@article {pmid41341510,
year = {2025},
author = {Yang, J and Yang, F and Chen, G and Liu, M and Yuan, S and Zhang, TE},
title = {Receptor-mediated mitophagy: a new target of neurodegenerative diseases.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1665315},
pmid = {41341510},
issn = {1664-2295},
abstract = {Neurodegenerative diseases are a category of neurological conditions with high prevalence that pose major treatment challenges. Common pathologies involve protein accumulation and mitochondrial damage. Mitophagy maintains cellular homeostasis by removing defective mitochondria, which are associated with the pathogenesis of neurodegenerative diseases. Although the ubiquitin-dependent mitophagy mediated by the PINK1-Parkin pathway has been extensively studied, growing evidence indicates that receptor-mediated mitophagy plays a crucial compensatory role in neurons, particularly when the PINK1-Parkin pathway is impaired. This review focuses on the emerging field of receptor-mediated mitophagy, systematically elaborating its role as a key homeostatic mechanism operating independently of the canonical PINK1/Parkin pathway. It provides a focused analysis of the specific functions and activation mechanisms of key receptors-including BNIP3, NIX, FUNDC1, and AMBRA1-in models of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Furthermore, this review explores the clinical potential of targeting these specific receptors for precise intervention, aiming to provide a new theoretical foundation and direction for developing therapeutic strategies against neurodegenerative diseases.},
}

@article {pmid41330444,
year = {2025},
author = {Rosso, F and Magdalena, R and Torazza, C and Bacchetti, F and Milanese, M and Poletti, A and Bonanno, G and Cristofani, R and Bonifacino, T},
title = {Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?.},
journal = {Neurobiology of disease},
volume = {218},
number = {},
pages = {107203},
doi = {10.1016/j.nbd.2025.107203},
pmid = {41330444},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative non-cell-autonomous disease with no cure, thus research is intensely focused on identifying pharmacological targets. Several studies aimed to clarify the pathogenic mechanisms and involvement in various cell types. A crucial factor in ALS is autophagy, which plays a key role in degrading intracellular protein aggregates. The connection between ALS and autophagy is reinforced by the fact that several genes mutated in ALS are linked to fundamental aspects of autophagy. The blockage of the autophagic flux was observed in ALS motor neurons, where it occurs earlier than in glia. However, the inconsistent effects of autophagy modulators in preclinical and clinical studies indicate the need for a deeper understanding of the role of autophagy in other cell types, such as astrocytes, microglia, and oligodendrocytes. Astrocytes and microglia are significantly impacted by autophagy dysregulation, contributing to neurodegeneration in both mouse and human-derived models. Autophagy is overactivated early in the disease, even before symptoms appear. This overactivation is influenced by the timing and specific tissue involved. It can alter cells' immunophenotype, favouring proinflammatory responses and affecting the cellular environment and autophagy in the surrounding cells. In contrast, oligodendrocytes show mild autophagic alterations. Additionally, sex hormones may affect proper autophagy function and ALS progression. The lack of information on how sex influences autophagy in glia highlights the need for more nuanced investigation into this mechanism. Future research should focus on these aspects, paving the way for personalised pharmacological approaches that consider the roles of cell types, time of intervention, and sex.},
}

@article {pmid41328916,
year = {2025},
author = {Ahsan, A and Kar, O and Akter, K and Ta, HDK and Shen, CJ and Datta, K and Chatterjee, B and Huang, CC and Majumder, P},
title = {Regulatory Functions of TDP-43 and FMRP in Non-Neuronal Diseases: Are Co-Targeted mRNAs the Keys?.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {23},
pages = {e71292},
doi = {10.1096/fj.202502281R},
pmid = {41328916},
issn = {1530-6860},
support = {110-2320-B-038-090-MY3//National Science and Technology Council (NSTC)/ ; },
mesh = {Humans ; *Fragile X Mental Retardation Protein/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *RNA, Messenger/genetics/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/genetics ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Fragile X Syndrome/genetics/metabolism ; },
abstract = {RNA binding proteins (RBPs) act as the central nodal point in shaping the cellular transcriptome through their involvement in various aspects of RNA metabolism including stability, splicing, polyadenylation, modifications, translation and transport. Dysregulation in the function of various RBPs can be associated with different human pathophysiological conditions. Owing to their ability to regulate various RNA metabolism-associated processes, the same RBPs can functionally be involved in human pathologies with distinct underlying pathophysiological mechanisms. Two such important RBPs, namely TDP-43 and FMRP, have long been implicated respectively, in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) etc. and in neurodevelopmental diseases like fragile-X syndrome (FXS). However, numerous recent reports indicate that these ubiquitously expressed proteins can regulate important cellular functions and signaling cascades, misregulation which results in different disease phenotypes. In this review, the association of TDP-43 and FMRP with different non-neuronal disease mechanisms has been discussed. Furthermore, to anticipate yet-to-be-explored non-neuronal disease mechanisms involving mismanagement in co-regulation of spatial and temporal transport/translation processes of TDP-43 and FMRP targeted RNAs, as observed in neuronal diseases for example, autism, RNA target databases of these two proteins are compared followed by GO and KEGG analysis. The lists of RNAs co-targeted by TDP-43 and FMRP are presumably involved in different non-neuronal diseases and disease-associated mechanistic pathways and will open up new phases of research to establish new disease mechanism(s). Different disease mechanisms and their interconnections expectantly will also lead to the discovery of new drug targets.},
}

Humans
*Fragile X Mental Retardation Protein/metabolism/genetics
*DNA-Binding Proteins/metabolism/genetics
*RNA, Messenger/genetics/metabolism
Animals
*Neurodegenerative Diseases/metabolism/genetics
Amyotrophic Lateral Sclerosis/genetics/metabolism
Fragile X Syndrome/genetics/metabolism

@article {pmid41126461,
year = {2025},
author = {Ayton, S and Moreau, C and Devos, D and Bush, AI},
title = {Iron on trial: recasting the role of iron in neurodegeneration.},
journal = {Brain : a journal of neurology},
volume = {148},
number = {12},
pages = {4241-4247},
doi = {10.1093/brain/awaf398},
pmid = {41126461},
issn = {1460-2156},
support = {//National Health & Medical Research Council of Australia/ ; //Florey Institute of Neuroscience/ ; },
mesh = {Humans ; *Iron/metabolism ; *Neurodegenerative Diseases/metabolism/drug therapy ; *Brain/metabolism ; Iron Chelating Agents/therapeutic use ; Animals ; Oxidative Stress/physiology ; },
abstract = {Iron is critical for numerous neurophysiological functions, while its dysregulation is potentially hazardous for neurodegeneration through oxidative stress and ferroptosis. For decades, elevated brain iron levels observed in neurodegenerative diseases such as Alzheimer's, Parkinson's and amyotrophic lateral sclerosis was presumed to drive disease progression; a hypothesis that propelled clinical trials of strong iron chelators like deferiprone. Results from these trials, however, have challenged this paradigm, with deferiprone markedly worsening outcomes in patients with Alzheimer's disease and, in certain contexts, patients with Parkinson's disease. These findings underscore the vital role of iron for brain health and suggest functional compensatory mechanisms that could become deleterious at the extremes of iron distribution (both low and high levels). Here, we outline an evolving understanding of iron's role in neurodegeneration, and we explore pathways for therapeutic development strategies that mitigate potential iron-mediated damage, while preserving its essential functions in the brain.},
}

Humans
*Iron/metabolism
*Neurodegenerative Diseases/metabolism/drug therapy
*Brain/metabolism
Iron Chelating Agents/therapeutic use
Animals
Oxidative Stress/physiology

@article {pmid41328354,
year = {2026},
author = {Huang, Q and Wang, S and Liu, Z and Rao, L and Cheng, K and Mao, X},
title = {Engineering exosomes for targeted neurodegenerative therapy: innovations in biogenesis, drug loading, and clinical translation.},
journal = {Theranostics},
volume = {16},
number = {1},
pages = {545-579},
pmid = {41328354},
issn = {1838-7640},
mesh = {Humans ; *Exosomes/metabolism ; *Neurodegenerative Diseases/drug therapy/therapy ; Animals ; *Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism ; Bioengineering/methods ; Translational Research, Biomedical ; },
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and multiple sclerosis (MS), are characterized by progressive neuronal dysfunction and limited therapeutic options, largely due to the restrictive nature of the blood-brain barrier (BBB). Exosomes, naturally occurring extracellular vesicles (EVs), have gained attention as innovative drug delivery vehicles owing to their intrinsic ability to cross the BBB, minimal immunogenicity, high biocompatibility, and capability to carry diverse therapeutic cargos such as proteins, nucleic acids, and small molecules. Furthermore, exosomes can be bioengineered to enhance drug-loading efficiency and targeting specificity, positioning them as a versatile and effective platform for treating NDDs. In this review, we summarize recent advances in exosome biogenesis, secretion, and engineering, with an emphasis on innovative strategies for exosome isolation, drug loading, and surface modification. We further explore their roles in modulating neuroinflammation, promoting neural regeneration, and enabling precise therapeutic delivery. Critical challenges associated with large-scale production, quality control, and regulatory compliance under Good Manufacturing Practices (GMP) are also discussed. Collectively, these developments underscore the transformative potential of engineered exosomes in advancing precision therapies for neurodegenerative disorders and offer strategic insights into their clinical translation.},
}

Humans
*Exosomes/metabolism
*Neurodegenerative Diseases/drug therapy/therapy
Animals
*Drug Delivery Systems/methods
Blood-Brain Barrier/metabolism
Bioengineering/methods
Translational Research, Biomedical

@article {pmid41327675,
year = {2025},
author = {Kiristioglu, MO and Akova, B and Sogutlu Sari, E and Baykara, M},
title = {Anterior segment optical coherence tomography in corneal diseases: A bibliometric analysis and visualization research of global research trends (1994-2024).},
journal = {Medicine},
volume = {104},
number = {48},
pages = {e45679},
doi = {10.1097/MD.0000000000045679},
pmid = {41327675},
issn = {1536-5964},
mesh = {*Tomography, Optical Coherence/methods/trends ; *Bibliometrics ; Humans ; *Corneal Diseases/diagnostic imaging ; *Biomedical Research/trends ; *Anterior Eye Segment/diagnostic imaging ; },
abstract = {PURPOSE: This study provides a bibliometric analysis of global research on anterior segment optical coherence tomography (AS-OCT) in corneal diseases, mapping key research trajectories, collaborations, and emerging trends.

METHODS: A systematic search in the Web of Science Core Collection on January 1, 2025, retrieved 3634 records (1994-2024). After excluding non-English publications, non-ophthalmology studies, and non-corneal research, 2079 publications were analyzed using VOSviewer and CiteSpace for citation networks, coauthorship trends, and keyword co-occurrence.

RESULTS: AS-OCT research has grown significantly (Mann-Kendall τ = 0.929, P < .001). The United States led in publications (639 papers, 19,594 citations), followed by China (333 papers, 4502 citations). The University of California was the most productive institution. The first AS-OCT study, published in the Archives of Ophthalmology (1994) by Izatt JA et al, marked the field's inception. The most cited article was Huang et al's 1991 Science paper on optical coherence tomography. Recent trends highlight the integration of artificial intelligence, deep learning, and optical coherence elastography in AS-OCT applications. The top 3 contributing journals were Cornea, Journal of Refractive Surgery, and Journal of Cataract and Refractive Surgery. Coauthorship analysis identified Jodhbir S. Mehta and David Huang as central figures in AS-OCT research collaborations.

CONCLUSION: AS-OCT research has expanded significantly, enhancing diagnostics, surgical planning, and disease monitoring. Artificial intelligence-driven analytics and optical coherence elastography are promising future directions. This bibliometric analysis guides advancing AS-OCT research and clinical applications.},
}

*Tomography, Optical Coherence/methods/trends
*Bibliometrics
Humans
*Corneal Diseases/diagnostic imaging
*Biomedical Research/trends
*Anterior Eye Segment/diagnostic imaging

@article {pmid41327179,
year = {2025},
author = {Eshak, D and Arumugam, M},
title = {Nanomaterials: an overview of current trends and future prospects in neurological disorder treatment.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1366},
pmid = {41327179},
issn = {1479-5876},
mesh = {Humans ; *Nervous System Diseases/therapy/drug therapy ; *Nanostructures/therapeutic use/chemistry ; Animals ; Blood-Brain Barrier ; },
abstract = {The World Health Organization (WHO) has identified neurological disorders (NDs) as one of the major health concerns worldwide, resulting in high mortality rates. NDs are conditions affecting the central and peripheral nervous systems, including the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, neuromuscular junctions, and muscles. These neurological diseases include Alzheimer's disease, Parkinson's disease, glioma/brain cancer, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, neuroinfections, ischemic stroke, trauma, hypoxia/anoxia, and depression. Unfortunately, these disorders remain difficult to treat due to the limited ability of conventional drugs to cross the blood-brain barrier (BBB) and achieve significant pharmacological effects in the brain. There is an urgent need to develop methods that can enhance drug efficacy and bypass the BBB. The application of various nanomaterials represents a promising approach to address these neurological disorders. Drugs incorporated with nanomaterials help improve therapeutic outcomes, reduce toxicity, provide better stability, enable targeted delivery, and enhance drug loading capacity. Numerous types and morphologies of inorganic and organic nanomaterials are increasingly employed for treating NDs, including quantum dots, dendrimers, metal nanoparticles, polymeric nanoparticles, liposomes, carbon nanotubes, metal oxide nanoparticles, and micelles. Their exceptional properties such as sensitivity, selectivity, and potential to bypass the BBB make them suitable for both diagnosis and treatment of NDs. In this review article, we briefly summarize the etiology and pathophysiology of various NDs along with current literature highlighting the use of nanomaterials for treating neurological disorders.},
}

Humans
*Nervous System Diseases/therapy/drug therapy
*Nanostructures/therapeutic use/chemistry
Animals
Blood-Brain Barrier

@article {pmid41320876,
year = {2025},
author = {Tang, YB and Zhang, J and Liu, Q},
title = {tRNA-derived small noncoding RNAs: Roles in brain aging and neurodegenerative disorders.},
journal = {Zoological research},
volume = {46},
number = {6},
pages = {1575-1587},
doi = {10.24272/j.issn.2095-8137.2025.349},
pmid = {41320876},
issn = {2095-8137},
mesh = {*Aging/physiology ; *Neurodegenerative Diseases/genetics/metabolism ; Animals ; *Brain/physiology/metabolism ; *RNA, Transfer/metabolism/genetics ; *RNA, Small Untranslated/metabolism/genetics ; Humans ; },
abstract = {Transfer ribonucleic acid-derived small ribonucleic acids (tsRNAs) are an emerging class of regulatory noncoding RNAs produced through the precise cleavage of mature or precursor tRNAs (pre-tRNAs). Once considered degradation byproducts, tsRNAs are now recognized as key modulators of gene expression, epigenetic regulation, and cellular stress responses. In recent years, growing evidence has implicated tsRNAs in the aging process of the brain and in the pathogenesis of age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). These small RNAs are involved in modulating synaptic function, neuronal survival, and neuroinflammation, and their expression profiles are dynamically altered in response to aging and disease-associated stressors. This review summarizes the biogenesis, classification, and molecular and cellular mechanisms of tsRNAs, with an emphasis on their subcellular locations and associated biological functions. We further explore their roles in brain aging and age-related neurodegenerative diseases and the emerging potential of tsRNAs as biomarkers and therapeutic targets for age-related neurological disorders while highlighting current challenges and future directions in this rapidly advancing field.},
}

*Aging/physiology
*Neurodegenerative Diseases/genetics/metabolism
Animals
*Brain/physiology/metabolism
*RNA, Transfer/metabolism/genetics
*RNA, Small Untranslated/metabolism/genetics
Humans

@article {pmid41109516,
year = {2026},
author = {Pandya, K and Kumar, D},
title = {CRISPR/cas genome editing for neurodegenerative diseases: Mechanisms, therapeutic advances, and clinical prospects.},
journal = {Ageing research reviews},
volume = {113},
number = {},
pages = {102922},
doi = {10.1016/j.arr.2025.102922},
pmid = {41109516},
issn = {1872-9649},
mesh = {Humans ; *Gene Editing/methods/trends ; *Neurodegenerative Diseases/genetics/therapy ; *CRISPR-Cas Systems/genetics ; Animals ; *Genetic Therapy/methods/trends ; },
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Spinocerebral Ataxia (SCA), and Huntington's disease (HD) are major global health challenges. Current treatments are only symptomatic and do not address the underlying pathogenic genetic mechanisms. The development of the CRISPR/Cas genome editing technologies, has increased possibilities for targeted repair of pathological mutations. CRISPR/Cas9, Cas12, and Cas13 systems enable targeted editing and transcriptome modulation in various preclinical models. CRISPR/Cas9 disruption of mutant APP, Tau, and LRRK2 genes, reducing toxic protein aggregration in AD models has restored normal genetic function. While correction of CAG nucleotide repeats in HD, and reduction of alpha-synuclein expression in PD. RNA targeting systems like Cas13 offers additional therapeutics potential by selectively degrading disease assciated transcript without altering genomic DNA. Advancements in engineered Cas variants with enhanced specificity, such as SpCas9-HF1, base editors and prime editors, with innovative delivery strategies including adeno-associated virus (AAVs) and nanoparticle-based systems, have improved genome editing. However, challenges remain, including off-target effects, mosaicism, and delivery across the BBB, and long-term safety. Ethical consideration focuses on somatic versus germline editing, equitable access, and regulatory oversight. While somatic editing shows acceptance in treating neurological disorders. Germline interventions face strict regulations due to potential multigeneration impacts. Collectively, these technologies are the vanguard of precision molecular medicine, advancing from symptom management towards potentially curative gene therapies for neurological disorders.},
}

Humans
*Gene Editing/methods/trends
*Neurodegenerative Diseases/genetics/therapy
*CRISPR-Cas Systems/genetics
Animals
*Genetic Therapy/methods/trends

@article {pmid41319477,
year = {2025},
author = {Benussi, A and Vucic, S},
title = {Emergent technologies and applications of TMS and TMS-EEG in clinical neurophysiology for early and differential diagnosis: IFCN handbook chapter.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {182},
number = {},
pages = {2111459},
doi = {10.1016/j.clinph.2025.2111459},
pmid = {41319477},
issn = {1872-8952},
abstract = {This chapter examines how emerging neurophysiological technologies are transforming the early and differential diagnosis of neurological disorders. While imaging and fluid biomarkers have greatly advanced the field, they remain limited by cost, invasiveness, and their inability to directly capture dynamic brain activity. Neurophysiological techniques, particularly transcranial magnetic stimulation (TMS) and TMS combined with EEG, offer a unique, non-invasive means of probing cortical excitability, connectivity, and plasticity with millisecond precision. Recent technological and analytical breakthroughs are moving these approaches from research laboratories into clinical practice. By detecting subtle network dysfunctions that precede structural degeneration, they open the possibility of identifying disease in its prodromal or even presymptomatic stages, when interventions may be most effective. This chapter outlines the principles of advanced TMS paradigms and TMS-EEG and explores their application across a range of conditions, including amyotrophic lateral sclerosis, dementias, and movement disorders. It also highlights how integrating neurophysiological measures with blood-based biomarkers and computational tools, such as machine learning, can enhance diagnostic accuracy and guide individualized treatment strategies. Together, these innovations establish neurophysiology as a cornerstone of precision neurology, linking mechanistic insights to clinical decision-making and enabling earlier diagnosis, improved patient stratification, and more targeted therapeutic interventions.},
}

@article {pmid41314748,
year = {2025},
author = {Quadri, SN and Tiwari, S and Siddiqi, B and Fatima, S and Khan, MA and Abdin, MZ},
title = {Advanced neuroimaging in precision neurology: Tools, trends, and translational impact.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {221-246},
doi = {10.1016/bs.pbr.2025.08.005},
pmid = {41314748},
issn = {1875-7855},
mesh = {Humans ; *Neuroimaging/methods/trends ; *Neurodegenerative Diseases/diagnostic imaging ; *Precision Medicine/methods/trends ; Translational Research, Biomedical ; *Neurology/methods/trends ; Artificial Intelligence ; Machine Learning ; },
abstract = {Advances in neuroimaging are revolutionizing the landscape of precision neurology by enabling high-resolution, multimodal visualization of brain structure, function, and pathology. As traditional, symptom-based frameworks fall short in capturing the biological complexity of neurodegenerative diseases, imaging modalities such as structural MRI, diffusion tensor imaging, functional MRI, PET, and hybrid PET/MRI have emerged as essential tools for early diagnosis, patient stratification, and therapeutic monitoring. These technologies not only reveal hallmark features like hippocampal atrophy and disrupted neural networks but also uncover molecular signatures such as amyloid and tau deposition, synaptic density, and neuroinflammation. Integration with artificial intelligence (AI) and machine learning (ML) further enhances diagnostic precision by decoding subtle imaging patterns, facilitating subtype classification, and predicting disease progression. Despite transformative progress, disparities in access and implementation remain a critical challenge, particularly in low- and middle-income countries. This chapter provides a comprehensive overview of neuroimaging modalities, their diagnostic and prognostic relevance across major neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, ALS, and frontotemporal dementia and the evolving role of hybrid platforms and AI integration in shaping the future of individualized neurological care.},
}

Humans
*Neuroimaging/methods/trends
*Neurodegenerative Diseases/diagnostic imaging
*Precision Medicine/methods/trends
Translational Research, Biomedical
*Neurology/methods/trends
Artificial Intelligence
Machine Learning

@article {pmid41314746,
year = {2025},
author = {Ceballos, MWG and Sy, FFA and Akbar, A and Taofiq, A},
title = {Multi-omics integration in disease research.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {155-189},
doi = {10.1016/bs.pbr.2025.08.012},
pmid = {41314746},
issn = {1875-7855},
mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; *Proteomics/methods ; *Genomics/methods ; *Metabolomics/methods ; Animals ; Multiomics ; },
abstract = {Neurodegenerative diseases, marked by complex molecular mechanisms and diverse clinical features, challenge conventional research approaches. This chapter emphasizes the value of multi-omics integration in understanding the biology of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Genomic studies reveal risk variants such as APOE ε4 in Alzheimer's and rare mutations in familial forms. Transcriptomics highlights gene expression changes, including synaptic dysfunction in early Parkinson's and alternative splicing errors in TARDBP-related ALS. Proteomics identifies key protein aggregates like amyloid beta and alpha-synuclein, along with modifications such as hyperphosphorylated tau that correlate with cognitive decline. Metabolomics uncovers metabolic alterations, including mitochondrial dysfunction in Parkinson's and lipid peroxidation in ALS, which contribute to disease progression. By combining these layers with high-throughput tools like single-cell sequencing, spatial transcriptomics, and mass spectrometry, researchers can reconstruct molecular networks linking genetic risk, gene regulation, protein dysfunction, and metabolic imbalance. This approach enables patient stratification into molecular subtypes, such as neuroinflammatory clusters defined by microglial gene signatures and cytokine expression. Biomarkers from blood and cerebrospinal fluid allow for minimally invasive disease monitoring. Despite challenges such as data heterogeneity and limited standardization, multi-omics approaches support biomarker discovery and therapeutic development. Integrating these datasets with neuroimaging and digital tools enhances diagnostic precision and guides targeted interventions, such as antisense therapies for SOD1-linked ALS. Multi-omics integration is thus a critical foundation for advancing personalized strategies in neurodegenerative disease research.},
}

Humans
*Neurodegenerative Diseases/genetics/metabolism
*Proteomics/methods
*Genomics/methods
*Metabolomics/methods
Animals
Multiomics

@article {pmid41070448,
year = {2025},
author = {ElDabour, MA},
title = {Circumferential clues: strain patterns and arrhythmia risk in pulmonary regurgitation.},
journal = {Cardiology in the young},
volume = {35},
number = {11},
pages = {2332-2333},
doi = {10.1017/S1047951125110032},
pmid = {41070448},
issn = {1467-1107},
mesh = {Humans ; *Pulmonary Valve Insufficiency/physiopathology/complications/surgery ; *Tetralogy of Fallot/surgery/complications/physiopathology ; *Arrhythmias, Cardiac/etiology/physiopathology ; *Heart Ventricles/physiopathology/diagnostic imaging ; Risk Factors ; },
abstract = {Slim et al.'s paper provided an insight into the differences between repaired tetralogy of Fallot and isolated pulmonary regurgitation in their strain. Repaired tetralogy of Fallot had higher right ventricular circumferential strain, while isolated pulmonary regurgitation relied on longitudinal strain more. This allowed the authors to infer that repaired tetralogy of Fallot can withstand more chronic regurgitation before valve replacement is necessary. We highlighted new findings relevant to this paper. Arrhythmia in repaired tetralogy of Fallot is associated with a reduced global circumferential strain of the right ventricle. Specifically, a value of below -14% was associated with a 6.3 times increase in the risk for an arrhythmic event. We believe this would be beneficial for patients when considered for valve replacements, suggesting modification of current valve replacement guidelines to include strain thresholds alongside current volumetric thresholds. However, the data for isolated pulmonary regurgitation remains scarce. Further investigation is needed to provide clearer timelines for valve replacement. We emphasised the importance of exploring the underlying architecture of repaired tetralogy of Fallot patients' hearts and why they could generate more global circumferential strain. We acknowledged the broader effect of this paper and its specific benefit in our country, Egypt. This paper provided insights useful for broader global health impact, especially in low-income countries.},
}

Humans
*Pulmonary Valve Insufficiency/physiopathology/complications/surgery
*Tetralogy of Fallot/surgery/complications/physiopathology
*Arrhythmias, Cardiac/etiology/physiopathology
*Heart Ventricles/physiopathology/diagnostic imaging
Risk Factors

@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 {pmid40231507,
year = {2025},
author = {Tecalco-Cruz, AC and Ramirez-Jarquin, JO and Medina Abreu, KH and Palacios-Serrato, EG and Lopez-Canovas, L and Zepeda-Cervantes, J and Oropeza-Martínez, E},
title = {Molecular Interplay of ISG15/ISGylation in Neuropathologies.},
journal = {CNS & neurological disorders drug targets},
volume = {24},
number = {10},
pages = {723-730},
pmid = {40231507},
issn = {1996-3181},
support = {CCyT-2024-CON-07//CCyT-UACM/ ; },
mesh = {Humans ; *Ubiquitins/metabolism ; Animals ; *Cytokines/metabolism ; *Neurodegenerative Diseases/metabolism ; },
abstract = {ISG15 is a 15 kDa ubiquitin-like protein that covalently associates with its target proteins by a sequential enzymatic process known as ISGylation. Research on protein ISGylation has increased in recent years, and some studies have suggested that ISG15 is involved in neuroprotection and neurodegeneration mechanisms. This review outlines the current state of research on the implications of ISG15/ISGylation in other neuropathies such as malignant tumors, ataxia telangiectasia, ischemia, depression, and neurodegenerative diseases such as Alzheimer's, Parkinson's diseases, multiple sclerosis, and amyotrophic lateral sclerosis. Based on the studies reported to date, ISG15/ ISGylation promotes the progression of brain tumors such as glioblastoma. Moreover, ISG15/ ISGylation seems to play a dual role in neuropathies, demonstrating a neuroprotective effect when there is acute brain damage, but ISG15/ISGylation is associated with reduced neuroprotection when there is chronic damage, such as in neurodegenerative diseases.},
}

Humans
*Ubiquitins/metabolism
Animals
*Cytokines/metabolism
*Neurodegenerative Diseases/metabolism

@article {pmid41314745,
year = {2025},
author = {Fatima, S and Tiwari, S and Siddiqi, B and Quadri, SN and Abdin, MZ},
title = {Biomarkers: From early detection to treatment personalization.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {131-153},
doi = {10.1016/bs.pbr.2025.08.008},
pmid = {41314745},
issn = {1875-7855},
mesh = {Humans ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/diagnosis/therapy/metabolism ; *Precision Medicine/methods ; Early Diagnosis ; },
abstract = {Neurodegenerative disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), present increasing issues associated with the unavoidable aging of the world's population. These challenges are further highlighted by the socioeconomic consequences of these diseases. The identification and use of biomarkers for prompt diagnosis, careful observation, and efficient treatment approaches is essential to overcoming these obstacles. The primary methods for diagnosing neurodegenerative illnesses are invasive procedures like lumbar punctures to measure CSF fluid or functional brain imaging methods. Biomarkers for underlying proteinopathy in blood serum and cerebral fluid have been the focus of recent biological research, particularly in vivo. With their ability to provide novel pathways for early detection, illness progression tracking, and individualized treatment plans, biomarkers have become essential instruments in precision medicine. The classification of biomarkers including fluid, digital imaging, and molecular biomarkers is examined in this chapter, with an emphasis on their function in neurodegenerative diseases. In neurodegenerative illnesses and the aging brain, tau, amyloid-β, α-synuclein, and TDP-43 are commonly seen to be deposited together rather than separately. These may be disregarded, and it might be challenging to determine their clinicopathological significance. An overview of illness pathophysiology, diagnostic implications, and the most recent molecular and ultrastructural categories for neurodegenerative disorders are given in this chapter. Addressing these issues through interdisciplinary research and technological advancements will be crucial for the future of biomarker-driven precision medicine. This chapter provides an in-depth overview of the evolving landscape of biomarkers and their transformative impact on the early detection and personalized treatment of neurodegenerative diseases.},
}

Humans
*Biomarkers/metabolism
*Neurodegenerative Diseases/diagnosis/therapy/metabolism
*Precision Medicine/methods
Early Diagnosis

@article {pmid41314744,
year = {2025},
author = {Gunasekaran, B and Arifin, AH and Yu, WH and Hanafi, S and Rao, KDK and Salvamani, S},
title = {Precision medicine in neurodegenerative diseases: From research to clinical practice.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {1-52},
doi = {10.1016/bs.pbr.2025.08.006},
pmid = {41314744},
issn = {1875-7855},
mesh = {Humans ; *Precision Medicine/methods ; *Neurodegenerative Diseases/therapy/genetics/diagnosis ; Biomarkers ; },
abstract = {The chapter outlines how precision medicine is reshaping the way neurodegenerative diseases (NDs) which includes Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are understood, diagnosed, and treated. It discusses the limitations of current therapies, which mainly address symptoms without altering disease progression. Genetic and molecular factors that influence disease development are described, including distinctions between familial and sporadic forms. The chapter also covers the roles of epigenetic changes, gene expression, protein dysfunction, mitochondrial DNA, and non-coding RNAs in NDs. Biomarkers in blood and cerebrospinal fluid, along with imaging techniques and digital tools, are presented as key elements in early diagnosis and disease monitoring. Patient stratification based on clinical features, molecular profiles, and biomarkers helps guide treatment decisions and improve outcomes. The chapter reviews ongoing developments in genotype-based drug design, gene therapy, pharmacogenomics, and personalized lifestyle strategies. Clinical case studies show how these approaches are being used in practice. The chapter also discusses challenges in applying precision medicine, such as trial design, data integration, unequal access, and regulatory hurdles. Finally, it highlights the future tools like single-cell transcriptomics, digital twins, and global research collaborations that aim to bring precision approaches into everyday care.},
}

Humans
*Precision Medicine/methods
*Neurodegenerative Diseases/therapy/genetics/diagnosis
Biomarkers

@article {pmid41314255,
year = {2025},
author = {Odonchimed, S and Imamura, K and Inoue, H},
title = {Neurodegenerative Disease and Autophagy in iPSC models.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {104991},
doi = {10.1016/j.neures.2025.104991},
pmid = {41314255},
issn = {1872-8111},
abstract = {Neurodegenerative diseases are characterized by the gradual deterioration of specific neuronal populations, ultimately resulting in motor, cognitive, or behavioral impairments. Despite the worldwide increase in disease incidence, effective therapies remain unavailable. A common pathological hallmark of neurodegenerative diseases is the accumulation of misfolded protein aggregates, which impair normal cellular function. Accordingly, numerous studies and therapeutic strategies have focused on targeting these toxic aggregates and protein quality control via autophagy, a vital cellular recycling mechanism. Autophagy dysregulation has been implicated in the pathogenesis of several neurodegenerative diseases. Induced pluripotent stem cell (iPSC) technology has emerged as a powerful platform for modeling neurodegenerative diseases, and iPSC-derived models provide human-relevant systems for studying autophagic dysfunction in vitro. In this review, we discuss the key findings of recent studies investigating autophagy in iPSC-based models of neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and other diseases.},
}

@article {pmid41313410,
year = {2025},
author = {Goel, F and Singh, P and Rai, SN and Yadav, DK},
title = {Nrf2/Keap1 Signaling Axis in the Brain: Master Regulator of Oxidative Stress in Neurodegenerative and Psychiatric Disorders.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {197},
pmid = {41313410},
issn = {1559-1182},
mesh = {Humans ; *Kelch-Like ECH-Associated Protein 1/metabolism ; *NF-E2-Related Factor 2/metabolism ; *Signal Transduction/physiology ; *Oxidative Stress/physiology ; *Mental Disorders/metabolism/pathology ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Brain/metabolism/pathology ; },
abstract = {Oxidative stress is a crucial factor in the development of CNS disorders, including neurodegenerative and psychiatric conditions. The Nrf2/Keap1 signaling axis plays a central role in defending against oxidative damage by regulating antioxidant and cytoprotective gene expression. Beyond its antioxidant function, Nrf2 influences neurogenesis, synaptic plasticity, mitochondrial bioenergetics, and glial neuronal interactions, all of which are vital for maintaining neural integrity and cognitive performance. Dysregulation of this pathway through altered dimerization, post-translational modifications, or impaired regulation contributes to the pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, leading to protein aggregation, mitochondrial dysfunction, and neuroinflammation. Emerging evidence also implicates aberrant Nrf2 activity in psychiatric disorders such as depression, schizophrenia, and bipolar disorder, where redox imbalance and neuroimmune activation disrupt neural function. This review summarizes the molecular structure and regulation of the Nrf2/Keap1 pathway, including basal and stress-induced activation, post-translational modifications, and cross-talk with PI3K/Akt, MAPK, and NF-κB signaling. We highlight cell-type-specific roles of Nrf2 in neurons, astrocytes, and microglia, and the gene expression networks that drive CNS antioxidant and detoxification responses. Recent therapeutic strategies include natural and synthetic Nrf2 activators, gene therapy approaches, and nanotechnology-based delivery systems. While the translational potential of Nrf2-targeted interventions is considerable, challenges remain, including risks of overactivation and oncogenicity, lack of reliable biomarkers, and barriers related to blood-brain barrier permeability, dose, timing, and bioavailability. By integrating advances in neuroscience, pharmacology, and molecular medicine, this review emphasizes the promise of Nrf2 as a unifying therapeutic target across diverse CNS pathologies. Future directions include precision modulation through epigenetic regulation and circRNAs, as well as personalized pharmacotherapy. The Nrf2/Keap1 axis represents a multidisciplinary platform for developing multimodal interventions to preserve brain health in neurodegenerative and psychiatric disorders.},
}

Humans
*Kelch-Like ECH-Associated Protein 1/metabolism
*NF-E2-Related Factor 2/metabolism
*Signal Transduction/physiology
*Oxidative Stress/physiology
*Mental Disorders/metabolism/pathology
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Brain/metabolism/pathology

@article {pmid41309196,
year = {2025},
author = {Jamwal, RS and Sharma, B and Minerva, and Gupta, A and Misri, S and Shankaryan, R and Shah, R and Kumar, R},
title = {Protein misfolding and its dual role in neurodegeneration and cancer progression.},
journal = {Advances in protein chemistry and structural biology},
volume = {148},
number = {},
pages = {355-377},
doi = {10.1016/bs.apcsb.2025.10.001},
pmid = {41309196},
issn = {1876-1631},
mesh = {Humans ; *Neoplasms/metabolism/pathology ; *Protein Folding ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Disease Progression ; Unfolded Protein Response ; },
abstract = {Protein misfolding is a fundamental biological process with profound implications for human health and disease. Typically, proteins assume precise three-dimensional structures to perform their functions, a process safeguarded by the proteostasis network, which comprises molecular chaperones, the ubiquitin-proteasome system (UPS), and autophagy. However, genetic mutations, oxidative stress, and environmental insults can disrupt folding, leading to the accumulation of non-functional or toxic conformations. In neurodegenerative diseases such as Huntington's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral Sclerosis (ALS), chronic misfolding results in toxic protein aggregates like amyloid-β, tau, and α-synuclein. These disrupt synaptic function, induce oxidative and nitrosative stress, and trigger apoptosis, ultimately leading to progressive neuronal loss. Dysregulation of the unfolded protein response (UPR) and weakened proteostasis with aging exacerbate disease pathology. In contrast, cancer cells utilize protein misfolding to enhance their survival and progression. Misfolded oncoproteins, such as mutant p53, not only evade degradation but also acquire oncogenic properties. Tumor cells hijack the UPR and chaperone networks, upregulate heat shock proteins, and manipulate oxidative stress responses to withstand hypoxia, nutrient deprivation, and rapid proliferation. Cancer stem cells (CSCs) further adapt to proteotoxic stress, contributing to tumor heterogeneity, therapy resistance, and immune evasion. The dual role of protein misfolding, driving degeneration in neurons while supporting proliferation in tumors, underscores its centrality in disease biology. Future research should focus on identifying early biomarkers of proteostasis imbalance and exploiting shared molecular pathways for the development of novel therapeutic interventions.},
}

Humans
*Neoplasms/metabolism/pathology
*Protein Folding
*Neurodegenerative Diseases/metabolism/pathology
Animals
Disease Progression
Unfolded Protein Response

@article {pmid41303502,
year = {2025},
author = {Hassan, M and Shahzadi, S and Moustafa, AA and Kloczkowski, A},
title = {Neurodegeneration Through the Lens of Bioinformatics Approaches: Computational Mechanisms of Protein Misfolding.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303502},
issn = {1422-0067},
support = {1R01HG012117-04/NH/NIH HHS/United States ; },
mesh = {Humans ; *Computational Biology/methods ; *Neurodegenerative Diseases/metabolism ; *Protein Folding ; Animals ; Protein Aggregates ; Protein Aggregation, Pathological/metabolism ; },
abstract = {Protein and peptide aggregation has become a prominent focus in biomedical research due to its critical role in the development of neurodegenerative diseases (NDs) and its relevance to industrial applications. Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are closely associated with abnormal aggregation processes, highlighting the need for a deeper understanding of their molecular mechanisms. In recent years, a wide range of computational methods, bioinformatics tools, and curated databases have been developed to predict and analyze sequences and structures that are prone to aggregation. These in silico approaches offer valuable insights into the underlying principles of aggregation and contribute to the identification of potential therapeutic targets. This review provides a concise overview of the current bioinformatics resources and computational techniques available for studying protein and peptide aggregation, intending to guide future research efforts in the field of neurodegenerative disease modeling and drug discovery.},
}

Humans
*Computational Biology/methods
*Neurodegenerative Diseases/metabolism
*Protein Folding
Animals
Protein Aggregates
Protein Aggregation, Pathological/metabolism

@article {pmid41302089,
year = {2025},
author = {Anjum, F and Hulbah, MJ and Shamsi, A and Mohammad, T},
title = {Exploring TANK-Binding Kinase 1 in Amyotrophic Lateral Sclerosis: From Structural Mechanisms to Machine Learning-Guided Therapeutics.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/life15111665},
pmid = {41302089},
issn = {2075-1729},
support = {KSRG-2024-446//King Salman Center for Disability Research/ ; },
abstract = {TANK-binding kinase 1 (TBK1) has emerged as one of the most compelling genetic contributors to amyotrophic lateral sclerosis (ALS), with heterozygous loss-of-function and pathogenic missense variants identified in patients across the ALS-frontotemporal dementia (FTD) spectrum. TBK1 participates in various core cellular processes associated with motor neuron vulnerability, including autophagy, mitophagy, and innate immune regulation, indicating that TBK1 is likely a key determinant of ALS pathogenesis. Structurally, TBK1 exhibits a trimodular organization comprising a kinase domain, a ubiquitin-like domain, and a scaffold/dimerization domain. Multiple experimentally resolved conformations and inhibitor-bound complexes provide a foundation for structure-guided therapeutic design. Here, we synthesize current genetic and mechanistic evidence linking TBK1 dysfunction to ALS, emphasizing its dual roles in autophagy and neuroinflammation. We also summarize advances in structure-based and AI-assisted drug discovery approaches targeting TBK1. Finally, we outline key translational challenges, including isoform selectivity, biomarker validation, and central nervous system (CNS) delivery, highlighting TBK1 as a promising yet complex therapeutic target in ALS. By integrating computational modeling, machine learning frameworks, and experimental pharmacology, future research may accelerate the translation of TBK1 modulators into clinically effective therapies.},
}

@article {pmid41300346,
year = {2025},
author = {Yeasmin, A and Torrente, MP},
title = {Histone Post-Translational Modifications and DNA Double-Strand Break Repair in Neurodegenerative Diseases: An Epigenetic Perspective.},
journal = {Biology},
volume = {14},
number = {11},
pages = {},
doi = {10.3390/biology14111556},
pmid = {41300346},
issn = {2079-7737},
support = {1R15NS125394-01/NH/NIH HHS/United States ; },
abstract = {DNA damage is a hallmark of the fatal process of neurodegeneration in the central nervous system (CNS). As neurons are terminally differentiated, they accumulate metabolic and oxidative burdens over their whole life span. Unrepaired DNA develops into DNA double-strand breaks (DSBs), which are repaired through homologous recombination (HR) or non-homologous end joining (NHEJ). Being post-mitotic and unable to normally undergo HR, damage and defective repair is especially burdensome to CNS neurons. Current research has not produced treatment to prevent and halt progression of neurodegeneration. Hence, novel targeting strategies are desperately needed. Recent investigations in histone post-translational modifications (PTMs) reveal new mechanistic insight and highlight unexplored targets to ameliorate neurodegeneration. As various histone PTMs dictate and facilitate DSB repair, they represent an underexploited area in investigating DNA damage and incorrect repair aiding neurodegeneration. Here, we review the histone PTM alterations in several neurodegenerative diseases: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia, Parkinson's Disease, Alzheimer's Diseases, Multiple Sclerosis, and Huntington's Disease. These findings emphasize that histone PTM alterations can enable an aberrant DNA damage response (DDR) leading to neurodegeneration. Further research into the connections between histone PTMs and DNA damage in decaying neurons will illuminate novel targets to dampen the aberrant DDR and promote neuronal survival.},
}

@article {pmid41299417,
year = {2025},
author = {Wang, J and Zhu, M and Smith, RD},
title = {Prevalence, incidence and risk factors of syphilis among men who have sex with men in China from 2013 to 2025: a systematic review and meta-analysis.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-025-12176-8},
pmid = {41299417},
issn = {1471-2334},
abstract = {BACKGROUND: Syphilis has re-emerged in China in recent decades, particularly among men who have sex with men (MSM). We aimed to assess the prevalence, incidence, and associated factors of syphilis among MSM in China.

METHODS: We systematically searched major English (MEDLINE via PubMed, Web of Science, Embase, Scopus, Cochrane Library) and Chinese (CNKI, Wanfang, CBM, VIP, Airiti Library) databases for studies on syphilis prevalence or incidence among MSM in China published from January 1, 2013 to March 1, 2025. Study qualities were evaluated using the Hoy et al.'s risk-of-bias tool and the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to estimate pooled syphilis prevalence (%) and incidence (per 100 person-years, PYs) with 95% confidence intervals (CIs). Meta-regression analyses were performed to assess differences across subgroups.

RESULTS: A total of 441 studies (429 prevalence and 33 incidence) were included. The pooled syphilis prevalence among general MSM was 8.8% (95% CI: 8.3-9.4). Study location (R²=0.13) and study year (R²=0.11) each contributed significantly to the high heterogeneity observed (I² = 98.5%) among the general MSM prevalence studies. MSM with high-risk sexual behaviors or related risk factors exhibited higher prevalence. The pooled incidence among all MSM was 7.8 per 100 PYs (95% CI: 6.0-9.8), with similarly high heterogeneity (I² = 96.4%). Both syphilis prevalence and incidence declined over time.

CONCLUSION: Syphilis prevalence and incidence remain high among high-risk MSM subgroups in China. More rigorous studies and targeted interventions are needed to obtain more accurate estimates and to further reduce syphilis infection rates.},
}

@article {pmid41295414,
year = {2025},
author = {Favari, E and Parolini, C},
title = {Marine Bioactive Components and Chronic Neuroinflammation: Focus on Neurodegenerative Disease.},
journal = {Marine drugs},
volume = {23},
number = {11},
pages = {},
pmid = {41295414},
issn = {1660-3397},
support = {NA//MUR Progetto Eccellenza/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Neuroinflammatory Diseases/drug therapy ; *Aquatic Organisms/chemistry ; Oxidative Stress/drug effects ; Inflammation/drug therapy ; },
abstract = {Advances in neuroscience, immunology, and neuroimmunology have revealed that the nervous and immune systems form a bidirectional integrated network, ranging from regulating inflammation to directing stress responses, pivotal for the maintenance of the brain-body physiology. Like peripheral inflammation, neuroinflammation is a conserved process aimed at activating innate/adaptive immune and non-immune cells to effectively deal with bacteria, viruses, toxins, and injuries, and eventually at removing the microbial pathogens and supporting tissue repair and recovery. A failure of this process or the permanent release of pro-inflammatory mediators causes a condition called "chronic low-grade neuroinflammation" resulting in tissue damage and an increased risk of developing neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Marine-derived bioactive components are able to modulate lipid and glucose metabolism as well as inflammation and oxidative stress. In this review, we describe the neuroinflammatory process and its involvement in the pathogenesis and progression of AD, PD, MS, and ALS. Then, we discuss the potential therapeutic efficacy of select marine-derived bioactive components.},
}

Humans
*Neurodegenerative Diseases/drug therapy
Animals
*Neuroinflammatory Diseases/drug therapy
*Aquatic Organisms/chemistry
Oxidative Stress/drug effects
Inflammation/drug therapy

@article {pmid41294873,
year = {2025},
author = {Wang, S and Feng, Z and Wu, H and Wang, S and Qin, S and Wang, X and Zhou, F and Zheng, K and Huang, X and Liu, X},
title = {The m[6]A Modification in Neurodegenerative Disease: A Cellular Perspective.},
journal = {Cells},
volume = {14},
number = {22},
pages = {},
pmid = {41294873},
issn = {2073-4409},
support = {BK20231347//Natural Science Foundation of Jiangsu Province/ ; 81971179//National Natural Science Foundation of China/ ; Z2019035//Jiangsu Commission of Health/ ; 20KJA320004//Jiangsu Provincial Department of Education/ ; KC23242//Technology Innovation Foundation of Xuzhou City/ ; JBGS202202//Open Competition Grant of Xuzhou Medical University/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; *Adenosine/analogs & derivatives/metabolism/genetics ; Animals ; Neurons/metabolism ; },
abstract = {N6-methyladenosine (m[6]A) is the most abundant internal RNA modification in eukaryotes and plays a critical role in gene expression regulation by influencing RNA stability, splicing, nuclear export, and translation. Emerging evidence suggests that dysregulation of m[6]A contributes to neuroinflammation, neurotoxicity, and synaptic dysfunction-key features of neurodegenerative diseases. This review aims to examine the role of m6A modification in neurodegenerative diseases from a cell-type-specific perspective. We systematically reviewed recent studies investigating m[6]A modifications in neurons and glial cells. Data from transcriptomic, epitranscriptomic, and functional studies were analyzed to understand how m[6]A dynamics influence disease-related processes. Findings indicate that m[6]A modifications regulate neuroinflammation and immune responses in microglia, modulate astrocytic support functions, affect myelination through oligodendrocytes, and alter m[6]A patterns in neurons, impacting synaptic plasticity, stress responses, and neuronal survival. These cell-type-specific roles of m[6]A contribute to the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). Understanding m[6]A-modulated mechanisms in specific neural cell types may facilitate the development of targeted interventions for neurodegenerative diseases.},
}

Humans
*Neurodegenerative Diseases/genetics/metabolism/pathology
*Adenosine/analogs & derivatives/metabolism/genetics
Animals
Neurons/metabolism

@article {pmid41294805,
year = {2025},
author = {Xu, H and Zhou, K and Xia, L and Ren, K and Xu, Y},
title = {In-Depth Study of Low-Complexity Domains: From Structural Diversity to Disease Mechanisms.},
journal = {Cells},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/cells14221752},
pmid = {41294805},
issn = {2073-4409},
support = {31972537//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Protein Domains ; Animals ; Neurodegenerative Diseases/metabolism ; Intrinsically Disordered Proteins/chemistry/metabolism ; },
abstract = {Low-complexity domains (LCDs) are protein regions characterized by a simple amino acid composition and low sequence complexity, as they are typically composed of repeats or a limited set of a few amino acids. Historically dismissed as "garbage sequences", these regions are now acknowledged as critical functional elements. This review systematically explores the structural characteristics, biological functions, pathological roles, and research methodologies associated with LCDs. Structurally, LCDs are marked by intrinsic disorder and conformational dynamics, with their amino acid composition (e.g., G/Y-rich, Q-rich, S/R-rich, P-rich) dictating structural tendencies (e.g., β-sheet formation, phase separation ability). Functionally, LCDs mediate protein-protein interactions, drive liquid-liquid phase separation (LLPS) to form biomolecular condensates, and play roles in signal transduction, transcriptional regulation, cytoskeletal organization, and nuclear pore transportation. Pathologically, LCD dysfunction-such as aberrant phase separation or aggregation-is implicated in neurodegenerative diseases (e.g., ALS, AD), cancer (e.g., Ewing sarcoma), and prion diseases. We also summarize the methodological advances in LCD research, including biochemical (CD, NMR), structural (cryo-EM, HDX-MS), cellular (fluorescence microscopy), and computational (MD simulations, AI prediction) approaches. Finally, we highlight current challenges (e.g., structural heterogeneity, causal ambiguity of phase separation) and future directions (e.g., single-molecule techniques, AI-driven LCD design, targeted therapies). This review provides a comprehensive perspective on LCDs, illuminating their pivotal roles in cellular physiology and disease, and offering insights for future research and therapeutic development.},
}

Humans
Protein Domains
Animals
Neurodegenerative Diseases/metabolism
Intrinsically Disordered Proteins/chemistry/metabolism

@article {pmid41294799,
year = {2025},
author = {Medigovic, G and Rachamala, HK and Dutta, SK and Pal, K},
title = {Structural and Functional Perspectives of Optineurin in Autophagy, Immune Signaling, and Cancer.},
journal = {Cells},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/cells14221746},
pmid = {41294799},
issn = {2073-4409},
support = {W81XWH-21-1-0678//Department of Defense Congressionally Directed Medical Research Program/ ; R56HL160545//The National Heart, Lung, and Blood Institute/ ; },
mesh = {Humans ; *Autophagy ; *Neoplasms/immunology/metabolism/pathology ; *Membrane Transport Proteins/chemistry/metabolism ; *Signal Transduction ; *Cell Cycle Proteins/chemistry/metabolism ; Animals ; *Transcription Factor TFIIIA/metabolism/chemistry/genetics ; },
abstract = {Optineurin (OPTN) is a multifunctional adaptor protein that regulates diverse cellular processes, including inflammatory signaling, autophagy, vesicular trafficking, and immune responses. This multifaceted role of OPTN is made possible by the presence of a complex structure comprising multiple domains that interact with different proteins to exert various functions important for modulating key signaling processes. Mutations in OPTN are linked with several human pathologies including glaucoma, Paget's disease of bone, Crohn's disease, and neurodegenerative diseases such as amyotrophic lateral sclerosis, and dementia. Emerging evidence suggests that OPTN has a complex and context-dependent role in cancer biology as well. It is upregulated in pancreatic ductal adenocarcinoma and hepatocellular carcinoma but downregulated in lung and colorectal cancers, indicating its dual role as a potential oncogene or tumor suppressor depending on the cellular environment. Additionally, OPTN plays a critical role in preventing immune evasion in colorectal cancer by maintaining interferon-gamma receptor 1 (IFNGR1) expression and supporting dendritic cell-mediated T-cell priming, thereby enhancing antitumor immune responses. Despite its significance in oncogenic pathways and immune regulation, the therapeutic potential of targeting OPTN in cancer remains largely unexplored. This review aims to provide a comprehensive understanding of OPTN's pleiotropic functions, highlighting its role in autophagy, inflammation, immune surveillance, and cancer progression. By elucidating its diverse regulatory mechanisms, we seek to encourage further research into the therapeutic implications of OPTN in cancer treatment and immunotherapy.},
}

Humans
*Autophagy
*Neoplasms/immunology/metabolism/pathology
*Membrane Transport Proteins/chemistry/metabolism
*Signal Transduction
*Cell Cycle Proteins/chemistry/metabolism
Animals
*Transcription Factor TFIIIA/metabolism/chemistry/genetics

@article {pmid41291690,
year = {2025},
author = {Mac Conghail, L and Parker, S and Matthews, A and Burke, S},
title = {Examining the roles, relationships and power dynamics shaping universal health system policy processes in high- and upper-middle-income countries: a scoping review.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-025-13773-8},
pmid = {41291690},
issn = {1472-6963},
support = {SPHeRE/2018/1/HRBI_/Health Research Board/Ireland ; },
abstract = {BACKGROUND: Policies for universal health systems aim to provide equitable access to quality healthcare. However, achieving this remains a complex goal in high and upper-middle-income countries. Despite widespread efforts, universal health system reforms vary significantly, shaped by historical, political, and economic contexts. Understanding the policy process, including the roles of various actors and institutions, is essential to improving policy effectiveness and achieving equitable health systems. This scoping review examines the literature on policy processes, stakeholder influences, and contextual factors shaping policies for universal health system reforms.

METHODS: A systematic search of peer-reviewed and grey literature from 2014 to 2024 was conducted using five academic databases and Google Scholar. Seventy-four studies focused on policies for universal health systems in high and upper-middle-income countries. Data was examined in two phases. First, a descriptive analysis explored the geographic and economic contexts of the studies and their representation across stages of the policy cycle, including agenda-setting, formulation, adoption implementation, and evaluation. Topp et al.'s framework was then used to examine the influence of key actors, focusing on their relationships, power sources, and societal expressions of power.

RESULTS: The review revealed significant geographical disparities, representing only 30% of eligible countries. Most studies focused on early policy stages, with limited attention to implementation and evaluation. A predominance of qualitative research facilitated contextual insights, yet the underrepresentation of quantitative and mixed methods approaches restricted opportunities for integrated analysis. Crises and ideological shifts were drivers of policy momentum, catalysing changes in universal health system reforms. Governments played a central role, supported or contested by civic groups, professional associations, and academia. Media often influenced public discourse and policy perceptions, amplifying or challenging reform narratives. Persistent challenges included fragmented systems, equity-efficiency tensions, and definitional ambiguities, undermining policy coherence and sustainability.

CONCLUSIONS: The review underscores the need for a broader 'universal' framework for understanding health system reform and prioritising equity, quality, and sustainability. Adaptive health systems, robust institutions, and standardised frameworks to address political, economic, and ideological barriers are crucial. Future research must evaluate equity impacts, refine policy design, and explore mechanisms to align reforms with universal health system principles and goals.},
}

@article {pmid41291238,
year = {2025},
author = {Li, H and Yu, C and Markovic, T and Nestler, EJ and Dong, Y},
title = {Chemical strategies for brain delivery of genomic therapy.},
journal = {Nature reviews. Chemistry},
volume = {},
number = {},
pages = {},
pmid = {41291238},
issn = {2397-3358},
abstract = {Genomic therapy has emerged as a transformative strategy for the prevention, diagnosis and treatment of a wide array of diseases, including Alzheimer's disease, amyotrophic lateral sclerosis and other CNS-related diseases. Recent developments in chemical strategies and delivery platforms have enhanced the potential of genomic therapies for brain disorders. In this Review, we summarize such strategies, focusing on advances in delivery platforms such as lipid nanoparticles, polymers and oligonucleotide conjugates to facilitate the brain delivery of DNA-based or RNA-based therapeutics into the CNS. We present an overview of the chemical structures and functional moieties of lipids, polymers and oligonucleotides used in these platforms. Lastly, we provide an outlook on future chemical directions to further improve the delivery of genomic medicines to the brain.},
}

@article {pmid41289739,
year = {2025},
author = {Dakroub, F and Awada, B and Abdelhady, S and Shaito, AA and Eid, AH and Walker, J and Mondello, S and Bondi, CO and Moro, F and Elgendy, B and Wang, KK and Zanier, ER and Mechref, Y and Kobeissy, F},
title = {Edaravone: Advances on cytoprotective effects, pharmacological properties, and mechanisms of action.},
journal = {Pharmacological reviews},
volume = {78},
number = {1},
pages = {100101},
doi = {10.1016/j.pharmr.2025.100101},
pmid = {41289739},
issn = {1521-0081},
abstract = {Neurological diseases often lead to life-altering consequences, underscoring the urgent need for therapies that can reverse or mitigate their effects. Effective management of neurological disorders necessitates a thorough understanding of the common pathological mechanisms driving their onset and progression. Mitochondrial dysfunction and oxidative stress stand out as critical contributors to neuronal damage, implicated in traumatic brain injury, stroke, and amyotrophic lateral sclerosis. Disruptions in energy metabolism lead to the accumulation of reactive oxygen species and elevate the level of neural injury. Moreover, these imbalances disrupt cellular homeostasis and activate apoptotic pathways, further exacerbating neuronal loss and ultimately worsening the clinical prognosis. In this context, edaravone (Eda), a Food and Drug Administration-approved free radical scavenger, has emerged as a compelling candidate for the treatment of neuropathologies. This review provides a comprehensive overview of Eda, detailing its chemical structure and pharmacokinetic profile, with a focus on strategies to enhance its delivery to the central nervous system by modulating blood-brain barrier permeability or employing delivery systems that facilitate central nervous system penetration. Moreover, the review examines Eda's pharmacodynamic properties, including the signaling pathways it influences. The neurotherapeutic potential of Eda is further examined through in vitro and in vivo models of neurological disease. Insights from clinical trials are discussed to bridge the gap between preclinical findings and patient outcomes. Finally, the review highlights the synergistic effects of combining Eda with other pharmacological agents or therapeutic interventions, underscoring its promise as a versatile and indispensable treatment for neurological disorders. SIGNIFICANCE STATEMENT: Edaravone, a Food and Drug Administration-approved free radical scavenger, shows broad neuroprotective potential by mitigating oxidative stress and mitochondrial dysfunction across diverse neurological disorders, including stroke, amyotrophic lateral sclerosis, and traumatic brain injury. By synthesizing preclinical and clinical evidence, this review highlights edaravone's pleiotropic therapeutic actions, identifies translational challenges, and underscores its promise as a versatile treatment strategy for neurodegenerative and acute and chronic brain conditions.},
}

@article {pmid41287286,
year = {2025},
author = {Prema, SS and Shanmugamprema, D},
title = {Empowering Parent-Focused Involvement in Early Detection and Treatment of Eating Disorders.},
journal = {European eating disorders review : the journal of the Eating Disorders Association},
volume = {},
number = {},
pages = {},
doi = {10.1002/erv.70060},
pmid = {41287286},
issn = {1099-0968},
abstract = {OBJECTIVE: To critically appraise Sidari et al.'s pilot evaluation of the Strong Foundations programme - a 6-week pre-treatment, family-centred intervention that reconceptualises the waitlist as an active window for support, and to assess whether scalable caregiver interventions can improve clinical outcomes and treatment engagement.

METHOD: Critical synthesis of the pilot study's design, implementation, and outcomes. The programme delivered structured psychoeducation to parents alongside specialist medical oversight for adolescents during the pre-treatment period. We summarise reported process and clinical indicators, assess methodological strengths and limitations, and explore adaptations such as digital delivery, peer co-facilitation and primary care integration within stepped-care frameworks.

RESULTS: Participating parents reported increased caregiving confidence and understanding of treatment pathways. Adolescents demonstrated preliminary improvements in BMI, affective symptoms and eating-disorder psychopathology. Strengths included focus on an overlooked treatment interval and integrated medical support; limitations included small sample size, absence of a control condition, selection bias, and brief follow-up. Proposed adaptations may increase scalability while preserving family-centred elements.

CONCLUSIONS: Reframing waitlists as active therapeutic intervals via brief, caregiver-focused interventions are promising for improving early outcomes, uptake and retention. Larger, controlled trials of condensed and digitally enabled formats are needed to establish effectiveness, cost-effectiveness, implementation feasibility and generalisability.},
}

@article {pmid41283496,
year = {2025},
author = {D'Alatri, L and Marchese, MR and Tizio, A and Galli, J},
title = {Pathophysiology and Etiology of Brainstem-Related Dysphagia.},
journal = {Audiology research},
volume = {15},
number = {6},
pages = {},
pmid = {41283496},
issn = {2039-4330},
abstract = {BACKGROUND: Brainstem-related dysphagia represents a complex and severe form of neurogenic dysphagia (ND) arising from lesions that disrupt the central pattern generator (CPG) for swallowing located in the medulla oblongata.

METHODS: This paper explores the physiological basis of swallowing and its disruption in various brainstem pathologies.

RESULTS: The clinical presentation and electrophysiological evaluation of dysphagia are discussed, with a focus on volitional and spontaneous swallowing (SS) and the use of electromyography (EMG)-based assessment techniques.

CONCLUSIONS: Finally, therapeutic strategies are reviewed, including conventional rehabilitative methods, neuromuscular electrical stimulation, non-invasive brain stimulation, and invasive procedures such as neurobotulinum toxin-A (BoNT-A) injections, balloon dilation, and CP myotomy.},
}

@article {pmid41283303,
year = {2025},
author = {Bartoshyk, P and O'Caoimh, R},
title = {Update on Disease-Modifying Pharmacological Treatments for Frontotemporal Dementia (FTD): A Scoping Review of Registered Trials.},
journal = {NeuroSci},
volume = {6},
number = {4},
pages = {},
pmid = {41283303},
issn = {2673-4087},
abstract = {Frontotemporal dementia (FTD) represents a cluster of adult-onset neurodegenerative diseases resulting from a combination of genetic and epigenetic factors. Currently, treatment is symptomatic and there are no licensed disease-modifying therapies available. The aim of this review was to provide an overview of ongoing or recently completed clinical studies targeting disease modification in FTD. A structured search of interventional trials of pharmacological compounds was conducted on three clinical trial registries (National Library of Medicine Clinical Trials, European Union Clinical Trials, and the Australian New Zealand Clinical Trials registries) up to September 2025. Twelve interventional trials were found. Half targeted autosomal-dominant progranulin (GRN) mutations (n = 6) and half examined therapies targeting neuroinflammatory-induced sporadic FTD (n = 6). The interim results of the early-phase (1/2) randomized controlled trials (RCTs), comprising three ongoing gene replacement studies (PROCLAIM, ASPIRE-FTD, upliFT-D) and one immune-modulating monoclonal antibody (INFRONT, now in phase 3)-all targeting the FTD-GRN mutation-show safety, tolerability, and effectiveness in restoring progranulin levels. Two recently completed phase 2 RCTs for sporadic FTD targeting neuroinflammation, the PEA-FTD and C9orf72 ALS/FTD trials, show disease-modifying potential. While interim results from six trials suggest clear mechanistic efficacy, prospective high-quality later-phase RCTs are required to ascertain long-term clinical efficacy. Since familial FTD encompasses less than half of the people with this disease, it is important to continue exploring the underlying pathophysiology, neuroimmunology, and treatment of epigenetic-induced sporadic FTD.},
}

@article {pmid40721287,
year = {2025},
author = {Vyas, J and Johns, JR and Trivedi, A and Ali, FM and Ingram, JR and Salek, S and Finlay, AY},
title = {Systematic review of the use of the Dermatology Life Quality Index in routine clinical practice: evidence from 287 articles across 56 countries.},
journal = {Clinical and experimental dermatology},
volume = {50},
number = {12},
pages = {2456-2465},
doi = {10.1093/ced/llaf343},
pmid = {40721287},
issn = {1365-2230},
mesh = {Humans ; *Quality of Life ; *Skin Diseases/psychology ; *Dermatology ; },
abstract = {BACKGROUND: Although quality of life instruments are widely used in research, it is challenging to find evidence of their use in routine clinical use. The most widely used measure for skin disease burden is the Dermatology Life Quality Index (DLQI), and its scores have validated clinical meaning.

OBJECTIVES: To identify evidence of the use of the DLQI in routine clinical practice and explore the nature of its use.

METHODS: The study followed PRISMA guidelines, and the protocol was registered with PROSPERO. MEDLINE (Ovid), Embase, Scopus and CINAHL (EBSCO) databases were systematically searched for articles describing studies using the DLQI in routine clinical practice. Studies were excluded if participants were aged < 16 years and if there were predetermined treatment interventions, as in a clinical trial. Information was extracted on publications' authors' opinions on the use of the DLQI in their routine practice.

RESULTS: In total, 2178 publications were screened and 287 articles met the inclusion criteria, reporting on 112 diseases and describing 66 434 patients from 56 countries, using the DLQI in at least 29 languages. Of the studies, 121 (42.2%) were reported as retrospective and 63 (22.0%) as observational. Fifty-two (18.1%) stated DLQI data were retrieved from patient records, 29 (10.1%) as 'real life', 39 (13.6%) reported 'real-world data' and 47 (16.4%) used consecutive patient recruitment. In total, 264 (92.0%) studies were conducted in a single country; 96 (33.4%) were multicentred studies, whereas 171 (59.6%) were conducted at a single site. There were 93 (32.4%) that were conducted in hospitals, 66 (23.0%) specified outpatient clinics, 38 (13.2%) tertiary care, 33 (11.5%) clinics, 4 (1.4%) in the community, 18 (6.3%) in other settings and 35 (12.2%) were unspecified. The most common diseases in the study settings were psoriasis (106 studies, 36.9%), atopic dermatitis (32, 11.1%), urticaria (24, 8.4%), hidradenitis suppurativa (22, 7.7%) and vitiligo (17, 5.9%). Thirty studies (10.5%) used Hongbo et al.'s (J Invest Dermatol 2005; 125:659-64) DLQI score banding.

CONCLUSIONS: The DLQI was widely used in routine care locations internationally, informing clinical decisions and monitoring of treatment. The DLQI was embedded into some clinics' continuing routine practice.},
}

Humans
*Quality of Life
*Skin Diseases/psychology
*Dermatology

@article {pmid41282495,
year = {2025},
author = {Araújo, B and Serrenho, I and Valente da Silva, A and Marceta, BM and Baltazar, G},
title = {Mesenchymal stem cells in neurological disorders: Insights from clinical trials.},
journal = {Regenerative therapy},
volume = {30},
number = {},
pages = {1024-1035},
pmid = {41282495},
issn = {2352-3204},
abstract = {Mesenchymal stem cells (MSCs) exhibit unique properties that make them promising candidates for cell therapy, particularly in neurological disorders. They can be derived from various tissues, with bone marrow, adipose tissue, umbilical cord, and placenta being the most common sources. Evidence suggests that the tissue of origin significantly influences MSC characteristics, including secretome composition, proliferation rate, and adhesion capacity. Clinical trials have demonstrated the safety and therapeutic potential of MSCs in conditions such as spinal cord injury, multiple sclerosis, and stroke. MSC therapy has been associated with improvements in motor, sensory, and cognitive functions, as well as enhanced quality of life. Mechanistically, MSCs promote neuroprotection, reduce inflammation, and modulate immune responses. In spinal cord injury, intrathecal administration of adipose- and bone marrow-derived MSCs has led to significant functional recovery, with single high-dose treatments often yielding better outcomes than multiple lower doses. In amyotrophic lateral sclerosis, bone marrow-derived MSCs have shown potential in slowing disease progression, though higher doses do not always result in greater benefits. In multiple sclerosis, high doses of umbilical cord-derived MSCs improved quality of life and prevented disease progression, whereas lower doses of bone marrow-derived MSCs provided limited functional benefits. While MSC therapy is considered safe, patient responses vary, and a definitive correlation between administered dose and therapeutic effects remains elusive. The small number of studies using comparable protocols impedes comparison of other relevant factor, limits the drawing of conclusions and underscore the importance of developing standardized protocols to optimize MSC-based treatments and maximize their clinical efficacy.},
}

@article {pmid41277874,
year = {2025},
author = {Ferreira-Junior, JR and de Lima Camandona, V and Barros, MH},
title = {From Yeast to Therapeutics: Modeling Neurodegenerative Diseases in Saccharomyces cerevisiae.},
journal = {Yeast (Chichester, England)},
volume = {},
number = {},
pages = {},
doi = {10.1002/yea.70008},
pmid = {41277874},
issn = {1097-0061},
support = {//This study was supported by grants and fellowships from Fundacao de Amparo a Pesquisa de Sao Paulo (FAPESP 2024/01152-3; 2023/14056-0), Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico (CNPq 305054/2022-8), and Coordenacao de Aperfeicoamento de Pessoal de Nıvel Superior-Brasil (CAPES-Finance Code 001)./ ; },
abstract = {Here, we review the use of Saccharomyces cerevisiae as a powerful model organism for studying cellular processes implicated in neurodegenerative disorders, including stress responses, proteostasis impairment, and vesicle trafficking defects. Over the last two decades, baker's yeast models have been developed for complex diseases such as Parkinson's, Alzheimer's, Huntington's, and Amyotrophic lateral sclerosis (ALS). Yeast cells expressing human proteins, such as amyloid-β, α-synuclein, huntingtin, and TDP-43, have become crucial tools for high-throughput drug screening aimed at counteracting disease progression. These yeast models have unveiled key components involved in the metabolism and toxicity of these proteins, enabling the identification of interacting partners and novel factors within each pathway. Importantly, these pathways were subsequently shown to be conserved in mammalian models. Furthermore, drug candidates identified using yeast models have provided significant leads for drug discovery, highlighting their potential for developing treatments for these neurodegenerative diseases.},
}

@article {pmid41277110,
year = {2025},
author = {Lu, J and Di Florio, DN and Boya, P and Maday, S and Springer, W and Chu, CT},
title = {Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-43},
doi = {10.1080/15548627.2025.2581217},
pmid = {41277110},
issn = {1554-8635},
abstract = {The human brain is one of the most metabolically active tissues in the body, due in large part to the activity of trillions of synaptic connections. Under normal conditions, macroautophagy/autophagy at the synapse plays a crucial role in synaptic pruning and plasticity, which occurs physiologically in the absence of disease- or aging-related stressors. Disruption of autophagy has profound effects on neuron development, structure, function, and survival. Neurons are dependent upon maintaining high-quality mitochondria, and alterations in selective mitochondrial autophagy (mitophagy) are heavily implicated in both genetic and environmental etiologies of neurodegenerative diseases. The unique spatial and functional demands of neurons result in differences in the regulation of metabolic, autophagic, mitophagic and biosynthetic processes compared to other cell types. Here, we review recent advances in autophagy and mitophagy research with an emphasis on studies involving primary neurons in vitro and in vivo, glial cells, and iPSC-differentiated neurons. The synaptic functions of genes whose mutations implicate autophagic or mitophagic dysfunction in hereditary neurodegenerative and neurodevelopmental diseases are summarized. Finally, we discuss the diagnostic and therapeutic potentials of autophagy-related pathways.Abbreviations: AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; APP: amyloid beta precursor protein; ASD: autism-spectrum disorder; BDNF: brain-derived neurotrophic factor; BPAN: β-propeller protein associated neurodegeneration; CR: caloric restriction; ΔN111: deleted N-terminal region 111 residues; DLG4/PSD95: discs large MAGUK scaffold protein 4; ER: endoplasmic reticulum; FTD: frontotemporal dementia; HD: Huntington disease; LIR: LC3-interacting region; LRRK2: leucine rich repeat kinase 2; LTD: long-term depression; LTP: long-term potentiation; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OMM: outer mitochondrial membrane; PD: Parkinson spectrum diseases; PGRN: progranulin; PINK1: PTEN induced kinase 1; PRKA/PKA: protein kinase cAMP-activated; PtdIns3P: phosphatidylinositol-3-phosphate; p-S65-Ub: ubiquitin phosphorylated at serine 65; PTM: post-translational modification; TREM2: triggering receptor expressed on myeloid cells 2.},
}

@article {pmid41276866,
year = {2025},
author = {Raoufinia, R and Alyari, G and Nia, AT and Abbaszadegan, MR and Mahmoudi, A and Shafaeibajestan, S and Saburi, E and Tavakol-Afshari, J and Hassani, M and Jamali, F and Salari, S and Boroumand, AR and Rahimi, HR},
title = {Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies.},
journal = {Stem cell research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13287-025-04781-w},
pmid = {41276866},
issn = {1757-6512},
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the selective loss of motor neurons (MNs), leading to progressive muscle weakness, atrophy, and ultimately paralysis. This review provides a comprehensive overview of the molecular mechanisms underlying ALS pathogenesis, the genetic mutations associated with both familial and sporadic forms of the disease, and the latest therapeutic strategies aimed at mitigating disease progression. mutations in genes such as C9orf72, SOD1, TARDBP, and FUS have been implicated in ALS, with an intricate interplay of protein misfolding, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation contributing to motor neuron degeneration. While current FDA-approved treatments such as Riluzole and Edaravone offer only modest benefits and do not significantly halt disease progression. Emerging therapies, including gene therapies (e.g., antisense oligonucleotides (ASOs) and CRISPR/Cas9, stem cell-based approaches, and neurotrophic factor supplementation, are demonstrating promising results in preclinical and early-phase clinical trials. novel approaches aim to target, modulate, and promote regeneration, renewed hope for future ALS treatments. However, several challenges remain, including effective delivery methods, safety concerns, and the inherent complexity of ALS pathology, ongoing research continues to explore these innovative interventions with the goal of improving clinical outcomes for patients. This review highlights the importance of personalized therapeutic approaches and underscores the necessity of continued innovation in ALS research, with the ultimate goal of developing disease-modifying therapies and, potentially, a cure for this fatal condition.},
}

@article {pmid41273627,
year = {2025},
author = {Wang, W and Tan, S and Zuo, X and Gao, X and Ma, L and Sun, R and Liang, G and Yin, L and Pu, Y and Zhang, J},
title = {Brain Organoids in Neurodegenerative Disease Modeling: Advances, Applications and Future Perspectives.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {142},
pmid = {41273627},
issn = {1559-1182},
mesh = {*Organoids/pathology ; Humans ; *Neurodegenerative Diseases/pathology ; *Brain/pathology ; Animals ; Disease Models, Animal ; *Models, Biological ; },
abstract = {Neurodegenerative diseases (NDDs) represent incurable and debilitating conditions characterized by progressive deterioration of neurological function. Investigating neurodegeneration remains a critical global challenge in aging societies. Brain organoids-self-organizing three-dimensional structures derived from human pluripotent stem cells-recapitulate cell types and cytoarchitectures of the developing human brain. This in vitro model system has advanced our bridge between conventional two-dimensional cultures and in vivo models. Brain organoids emulate early neural tube formation, neuroepithelial differentiation, and whole-brain regionalization. Furthermore, region-specific organoid models now facilitate mechanistic investigation into acquired and inherited NDDs' pathogenesis, alongside drug discovery and toxicity screening. In this review, we (i) delineate the epidemiology and pathobiology of major NDDs, (ii) analyze limitations of current animal models, (iii) critically evaluate brain organoid generation methodologies, and (iv) focus on organoid applications in modeling Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS).},
}

*Organoids/pathology
Humans
*Neurodegenerative Diseases/pathology
*Brain/pathology
Animals
Disease Models, Animal
*Models, Biological

@article {pmid41272780,
year = {2025},
author = {Kumar, A and Shukla, S and Rai, A and Pathak, P and Narayan, KP},
title = {Concurrent nanotherapeutics and regulatory updates for the management of amyotrophic lateral sclerosis: a focused review for orphan drug (Tofersen).},
journal = {Orphanet journal of rare diseases},
volume = {20},
number = {1},
pages = {598},
pmid = {41272780},
issn = {1750-1172},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; Genetic Therapy/methods ; Orphan Drug Production ; *Oligonucleotides/therapeutic use ; United States Food and Drug Administration ; },
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder affecting nerve cells in the brain and spinal cord. With a global incidence of 1.9 to 6 per 100,000 people, ALS is slightly more common in men and prevalent in individuals over 60. However, this review provides a concise update on the regulatory landscape and therapeutic advancements in managing ALS, focusing on the recent approval of Tofersen, the first gene therapy specifically targeting SOD1 mutation-related ALS.

RESULTS: It highlights Tofersen unique role as an orphan drug approved by the US FDA, emphasizing its mechanism of action, gene silencing and its impact on reducing neurodegeneration. Additionally, the review synthesizes data from ongoing clinical trials, pharmacovigilance reports, and case studies to comprehensively understand Tofersen's safety, efficacy and market exclusivity. Beyond this, it explores the emerging potential of nanotherapeutic approaches to ALS treatment, identifying critical research gaps and future directions.

CONCLUSION: Integrating regulatory updates, clinical evidence, and innovative therapeutic strategies, the review uniquely contributes to the ALS literature by bridging current treatment realities with potential future therapies, aiming to inform researchers, clinicians, and policymakers on optimizing ALS management.},
}

*Amyotrophic Lateral Sclerosis/drug therapy
Humans
Genetic Therapy/methods
Orphan Drug Production
*Oligonucleotides/therapeutic use
United States Food and Drug Administration

@article {pmid41269421,
year = {2025},
author = {Asadinejad, H and Taherkhani, S and Golboos, SM and Azizi, Y and Mohammadkhanizadeh, A},
title = {Targeting Neurodegeneration with SGLT2is: From Molecular Mechanisms to Clinical Implications.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {119},
pmid = {41269421},
issn = {1559-1182},
mesh = {Humans ; *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; },
abstract = {Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a class of antidiabetic drugs that have demonstrated significant cardiovascular and renal benefits. Accumulating evidence suggests that SGLT2is also exert neuroprotective effects and may influence the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). SGLT2is modulate glucose metabolism, reduce oxidative stress, suppress inflammation, and enhance mitochondrial function. Beyond glycemic control, they show potential therapeutic effects in ameliorating the metabolic dysregulation associated with neurodegenerative pathologies. Current preclinical and clinical evidence including metabolic regulation, anti-inflammatory actions, and neuroprotective effects mediated through SGLT2is associated molecular pathways have been critically evaluated to delineate their therapeutic potential in neurodegenerative disorders. Although preclinical studies have shown promising results, more clinical trials are needed. This review highlights key research gaps and proposes future translational applications.},
}

Humans
*Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology
Animals
*Neurodegenerative Diseases/drug therapy/metabolism
*Neuroprotective Agents/therapeutic use/pharmacology

@article {pmid41268324,
year = {2025},
author = {Thakur, DK and Padole, S and Sarkar, T and Arumugam, S and Chattopadhyay, S},
title = {Liquid-Liquid Phase Separation: Mechanisms, Roles, and Implications in Cellular Function and Disease.},
journal = {FASEB bioAdvances},
volume = {7},
number = {11},
pages = {e70054},
pmid = {41268324},
issn = {2573-9832},
abstract = {Liquid-liquid phase separation is a basic biophysical process that creates essential membraneless organelles that support different cellular activities, including chromatin organization and gene expression. The malfunction of liquid-liquid phase separation (LLPS) plays a critical role in numerous diseases, such as neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), which involve TDP-43 and Tau, various cancers that utilize SPOP and YAP/TAZ proteins, and viral infections where pathogens use LLPS to replicate and avoid immune detection. This review brings together the fast-growing knowledge about LLPS across multiple scientific fields. The paper examines the physiological functions of LLPS along with its disease pathogenesis mechanisms and presents various experimental techniques (e.g., advanced microscopy, FRAP, FCS) for its investigation. It introduces new therapeutic approaches such as PTM modulation, small molecules like 1,6-hexanediol and Lipoamide, and advanced genetic tools including CRISPR and PROTACs like PSETAC, which also explores diagnostic applications. The thorough integration of knowledge presented here is essential to connect separate scientific findings while propelling research forward and turning LLPS discoveries into new biomedical developments.},
}

@article {pmid41263806,
year = {2025},
author = {Kalkowski, K},
title = {[Genetic and Molecular Pathomechanisms of Amyotrophic Lateral Sclerosis and Therapeutic Perspectives – Current State of Knowledge].},
journal = {Postepy biochemii},
volume = {71},
number = {3},
pages = {252-259},
doi = {10.18388/pb.2021_599},
pmid = {41263806},
issn = {0032-5422},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/therapy ; Humans ; Genetic Therapy ; Superoxide Dismutase-1/genetics ; C9orf72 Protein/genetics ; Mutation ; RNA-Binding Protein FUS/genetics ; DNA-Binding Proteins/genetics ; Protein Serine-Threonine Kinases/genetics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease leading to progressive degeneration of motor neurons, muscle weakness and respiratory failure. Despite intensive research, the pathomechanisms of ALS have not been fully elucidated. This article presents the current state of knowledge on the genetic and molecular mechanisms of this disease, with a focus on mutations in the SOD1, C9ORF72, TARDBP, FUS, TBK1 genes, as well as recent discoveries in this area. Key pathogenetic processes are discussed, including disruption of RNA homeostasis, oxidative stress, mitochondrial dysfunction and protein aggregation. In addition, current therapeutic strategies are reviewed, including both registered drugs, such as riluzole and edaravone, and modern approaches, such as gene therapy, antisense oligonucleotides, immunotherapy and gene editing technologies, including CRISPR/Cas9. Special attention was given to clinical trials and their potential impact on future treatment options for ALS.},
}

*Amyotrophic Lateral Sclerosis/genetics/therapy
Humans
Genetic Therapy
Superoxide Dismutase-1/genetics
C9orf72 Protein/genetics
Mutation
RNA-Binding Protein FUS/genetics
DNA-Binding Proteins/genetics
Protein Serine-Threonine Kinases/genetics

@article {pmid41260310,
year = {2025},
author = {Alberti, C and Parente, V and Corti, S and Sansone, VA},
title = {From molecular convergence to clinical divergence: Comparative pathogenic mechanisms and therapeutic trajectories in C9orf72-ALS/FTD and myotonic dystrophy.},
journal = {Neurobiology of disease},
volume = {217},
number = {},
pages = {107192},
doi = {10.1016/j.nbd.2025.107192},
pmid = {41260310},
issn = {1095-953X},
abstract = {Short tandem repeat expansions in C9orf72, DMPK, and CNBP genes cause amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) and myotonic dystrophy types 1 and 2 (DM1/DM2), respectively. Despite distinct clinical phenotypes, these disorders share convergent molecular mechanisms with tissue-specific vulnerability, offering a framework to inform precision therapeutic strategies. Shared pathogenic features include nuclear RNA foci sequestering RNA-binding proteins that disrupt splicing, and repeat-associated non-AUG translation generating toxic dipeptide repeat proteins. In C9orf72, GGGGCC repeats form RNA-driven condensates, including protein-free condensates, via G-quadruplex formation. Evidence also implicates autophagy-lysosome and mitochondrial dysfunction, suggesting a potential "two-hit" loss/gain-of-function model. Clinically, C9orf72 expansions primarily affect motor neurons and frontotemporal circuits, with ALS progression typically occurring over 2-5 years. Conversely, myotonic dystrophy manifests as a muscle-predominant multisystem disorder progressing over decades. Genomic instability contributes to disease variability, with anticipation and parent-of-origin effects strongest in DM1, not confirmed in DM2 and controversial in C9orf72. Sequence interruptions modulate repeat stability and phenotype, influencing diagnostic interpretation. Therapeutic development has yielded contrasting outcomes. Antisense oligonucleotides targeting C9orf72 achieved target engagement and reduced dipeptide repeat proteins but failed clinically, potentially due to sense-strand selectivity and persistence of TDP-43 pathology. In contrast, RNA-targeting conjugates for DM1 (delpacibart etedesiran and DYNE-101) received FDA Breakthrough Therapy designation. Therapeutic success depends on tissue accessibility and addressing both shared and circuit-specific pathogenic cascades. While nuclear RNA targets appear druggable in myotonic dystrophy, the bidirectional transcription and compartmentalized pathology of C9orf72 ALS/FTD may require multi-targeted approaches for precision medicine.},
}

@article {pmid41258317,
year = {2025},
author = {Wang, S and Zhang, X and Zhang, },
title = {Charting the landscape and evolution of research on cell death in acute lymphoblastic leukemia: a comprehensive bibliometric analysis (1990-2024).},
journal = {Discover oncology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s12672-025-04102-w},
pmid = {41258317},
issn = {2730-6011},
abstract = {BACKGROUND: The interplay between regulated cell death pathways and Acute Lymphoblastic Leukemia (ALL) pathobiology profoundly influences disease progression and therapeutic responses.

OBJECTIVE: This study performs a comprehensive bibliometric analysis to delineate the historical trajectory, current status, and emerging research frontiers concerning cell death in ALL from 1990 to 2024.

METHODS: This bibliometric analysis maps global research on cell death in ALL (1990-2024) using 4,111 publications from the Web of Science Core Collection using search terms related to cell death and ALL. VOSviewer and CiteSpace were utilized to analyze publication trends, geographical and institutional distributions, international collaborations, journal and author productivity and impact, co-citation networks (references, authors, journals), and keyword co-occurrence, clusters, and citation bursts.

RESULTS: Publications grew slowly (1990-1992), expanded rapidly (1993-2015, peak in 2015), then moderated. The United States dominated research output (33.69% publications, 68.41 citations/paper) and collaborated strongly with China, Italy, and the UK. The University of Texas System was the most productive institution (153 articles). Blood ranked first in publications (236) and co-citations (3403). Uckun authored the most papers (31), while Pui was the most co-cited author (736 co-citations). Keyword clusters revealed evolving foci: from apoptosis (1990s) to BH3-only proteins (2000s), with current frontiers in ​ferroptosis, CAR-T cells, and drug resistance. Terwilliger et al.'s review showed the strongest citation burst.

CONCLUSION: This study dilineates the intellectual landscape of cell death research in ALL, highlighting ferroptosis, immunotherapy integration, and resistance mechanisms as critical future directions to improve therapeutic outcomes.},
}

@article {pmid41251254,
year = {2025},
author = {Staehr-Rye, AK and Küchen, SHL and Salvesen, L and Blicher, J and Strange, DG and Svenstrup, K},
title = {[Chronic respiratory insufficiency in amyotrophic lateral sclerosis].},
journal = {Ugeskrift for laeger},
volume = {187},
number = {44},
pages = {},
doi = {10.61409/V03250140},
pmid = {41251254},
issn = {1603-6824},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/therapy/physiopathology ; *Respiratory Insufficiency/therapy/etiology/physiopathology ; Respiration, Artificial/methods ; Chronic Disease ; Noninvasive Ventilation ; Quality of Life ; },
abstract = {Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by progressive loss of motor neurons in the brain and spinal cord. As the disease progresses, respiratory function becomes increasingly compromised. Supporting respiratory function is the treatment with the greatest potential impact on life expectancy and should align with the patient's wishes to ensure quality of life. Optimal secretion management is essential for effective non-invasive mechanical ventilation therapy, as argued in this review. Home invasive mechanical ventilation is reserved for a small subset of patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/therapy/physiopathology
*Respiratory Insufficiency/therapy/etiology/physiopathology
Respiration, Artificial/methods
Chronic Disease
Noninvasive Ventilation
Quality of Life

@article {pmid41250117,
year = {2025},
author = {Kulcsárová, K and Piel, JHA and Schaeffer, E},
title = {Environmental toxins in neurodegeneration - a narrative review.},
journal = {Neurological research and practice},
volume = {7},
number = {1},
pages = {93},
pmid = {41250117},
issn = {2524-3489},
abstract = {As the global incidence of neurodegenerative disorders rises at a rate beyond what can be attributed solely to population aging, the role of modifiable risk factors has come into research spotlight to inform preventive strategies. While many lifestyle interventions can be implemented at an individual level, addressing environmental pollutants that drive neurodegeneration requires a collective effort involving both public and political engagement. This narrative review summarizes current evidence on the role of selected environmental toxins-pesticides, solvents, air pollution, and heavy metals-in the development of Parkinson's Disease, Alzheimer's Disease, and Amyotrophic Lateral Sclerosis. Drawing from epidemiological and experimental studies, we highlight associations between these exposures and neurodegeneration, as well as potential converging pathophysiological mechanisms such as neuroinflammation and proteinopathy. Understanding these links may help inform public health measures aimed at reducing the burden of these diseases.},
}

@article {pmid41099526,
year = {2025},
author = {Lami, R},
title = {From biocides to biology: multispecies biofilms as a sustainable, self-regenerating, and effective antifouling strategy.},
journal = {Applied and environmental microbiology},
volume = {91},
number = {11},
pages = {e0160925},
doi = {10.1128/aem.01609-25},
pmid = {41099526},
issn = {1098-5336},
mesh = {*Biofilms/drug effects/growth & development ; *Disinfectants/pharmacology ; *Biofouling/prevention & control ; Bacteria/drug effects ; },
abstract = {Finding antifouling strategies that are effective and environmentally safe remains a central challenge for maritime operations and ecosystem protection. Amador et al.'s article in Applied and Environmental Microbiology (91:e01392-25, 2025, https://doi.org/10.1128/aem.01392-25) proposes a bioinspired, applied-microbial-ecology solution: deliberately shaping pioneer biofilm communities, so they form a physical barrier against macrofouler settlement, avoiding biocides and low-adhesion inert coatings. Though focused on the ocean, this paradigm could inform broader anti-biofilm interventions across microbiology, reframing control as ecological steering rather than chemical suppression or materials-based design.},
}

*Biofilms/drug effects/growth & development
*Disinfectants/pharmacology
*Biofouling/prevention & control
Bacteria/drug effects

@article {pmid41248812,
year = {2025},
author = {Di Nunzio, M and Mignogna, ML and Bacigaluppi, M and Panina-Bordignon, P and Ragonese, P and Muzio, L and Summa, V and Martino, G},
title = {The role of dopaminergic signalling from physiology to neuroprotection in acute and chronic disorders.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107194},
doi = {10.1016/j.nbd.2025.107194},
pmid = {41248812},
issn = {1095-953X},
abstract = {The dopaminergic system plays a central role in neuromodulation, involving motor control, reward, and cognition, and exerting its effects through five G protein-coupled receptors (DRD1-DRD5) with distinct tissue distributions and signalling mechanisms. While dopaminergic alterations are known to be associated to neuropsychiatric and movement disorders such as schizophrenia, Parkinson's disease, and Huntington's disease, growing evidence highlights a broader role in neurological and neurodegenerative conditions. This review explores the dopaminergic system's pathophysiological involvement in acute and chronic diseases such as stroke, spinal cord (SCI), traumatic brain (TBI) injury, and amyotrophic lateral sclerosis (ALS). Beyond characterizing its dysfunction, we aim to examine how this disrupted signalling contributes to the neurodegeneration underlying the neurological and neurodegenerative disorders discussed here, along with the associated pathophysiological factors of inflammation and altered plasticity. We further discuss emerging data supporting the potential of dopamine-based interventions not only to modulate disease mechanisms, but also to confer neuroprotection and reduce tissue damage in both acute and progressive neurodegeneration, while also considering sex-related dopamine alterations. By integrating findings across diverse conditions, we underscore the importance of advancing dopaminergic research beyond classical disease models into novel therapeutic territory.},
}

@article {pmid41246746,
year = {2025},
author = {Bethea, JP and Sharma, H and Doberstein, N and Shenker, T and Gregory, B and Hoffman, R and Aizenman, D and Guirguis, G and Hoffmann, J and Tazani, S and Harris, Z and Costin, J},
title = {Application of Osteopathic Manipulative Treatment (OMT) in Neurodegenerative Disorders: A Scoping Review.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e94748},
doi = {10.7759/cureus.94748},
pmid = {41246746},
issn = {2168-8184},
abstract = {Neurodegenerative diseases are comprised of a host of chronic conditions that impair the central nervous system. Osteopathic manipulative treatment (OMT) consists of many non-invasive modalities that can be used to treat a wide variety of ailments and conditions. OMT is reported to increase the range of motion and lymphatic flow, as well as decrease pain in a wide array of disorders. However, the efficacy of using OMT in neurodegenerative disorders has not been well established. The objective of this scoping review is to map the evidence that pertains to the application of OMT in treating neurodegenerative disorders and identify the gaps in the literature on this subject. This study was designed according to the Joanna Briggs Institute (JBI) guidelines for scoping reviews to gather information on OMT's potential efficacy in managing Parkinson's disease (PD), Alzheimer's disease (AD) dementia, amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Peer-reviewed literature was collected through the Excerpta Medica database (EMBASE), Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE), and Web of Science. The criteria were limited to papers in English published between 1999 and 2023. The following search string was utilized: "osteopathic manipulative treatment" OR "osteopathic manipulation" AND "neurodegenerative disorders" OR "Alzheimer's disease" OR "dementia" OR "amyotrophic lateral sclerosis" OR "Parkinson's disease" OR "Huntington's chorea". One hundred and forty-three articles were identified following final screening and critical appraisal, with eleven articles selected for analysis in this study. Data from the selected articles demonstrated that OMT can possibly attenuate symptoms in patients diagnosed with neurodegenerative diseases. Studies in rats showed that OMT techniques were found to alter cholinergic neuronal genes, improve spatial learning and memory, reduce amyloid β protein levels, modulate synaptic transmission, and increase levels of the cytokines IL-1, IL-10, IL-13, RANTES, IL-17A, and EOTAXIN effects in AD dementia. ALS patients demonstrated a high level of satisfaction with OMT and did not report any adverse effects, though there was no decrease in pain or increased quality of life reported. PD patients reported improved postural stability, balance, and gait after OMT. No results were returned regarding OMT's effects on HD. Preliminary results in human PD and ALS patients who received OMT as an adjunct to traditional treatment regimens showed promising results, though few studies were found that address the topic, and the sample sizes of the studies that were found were small. There were no studies of the effects of OMT on human patients with AD or HD found, though preclinical studies in rats supported their trial in subsequent human studies. While current research on the impact of OMT on these neurodegenerative diseases is promising, there remain large gaps in the literature. Further research is necessary to support the use of and long-term efficacy of OMT in neurodegenerative diseases.},
}

@article {pmid41246229,
year = {2025},
author = {Şahin, TÖ and Cemali, Ö and Özdemir, M and Ayten, Ş and Ağagündüz, D},
title = {Flavonoids and phenolic compounds: a promising avenue for neurodegenerative disease therapy.},
journal = {Turkish journal of biology = Turk biyoloji dergisi},
volume = {49},
number = {5},
pages = {635-659},
doi = {10.55730/1300-0152.2767},
pmid = {41246229},
issn = {1303-6092},
abstract = {BACKGROUND/AIM: Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and ALS are characterized by a progressive loss of nerve cells, for which no definitive cure currently exists. These conditions share common pathological mechanisms, including chronic neuroinflammation, oxidative stress, protein aggregation, and mitochondrial dysfunction. Flavonoids and other plant-derived phenolic compounds have recently attracted attention for the treatment of such conditions due to their antiinflammatory and antioxidant properties. This review explores the neuroprotective mechanisms of flavonoids and evaluates their potential for the prevention and treatment of neurodegenerative diseases.

MATERIALS AND METHODS: A literature search of the Web of Science, PubMed, and ScienceDirect databases was conducted to evaluate the therapeutic potential of flavonoids and phenolic compounds against neurodegenerative diseases. The search terms included "polyphenols", "flavonoids", and related compounds, along with "Alzheimer's", "Parkinson's", "Huntington's", and "Amyotrophic lateral sclerosis". Eligible studies included clinical trials, randomized controlled trials, and in vitro and in vivo research published in English. Priority was given to studies from the last decade, although older but significant publications were also included.

RESULTS: The findings of multiple studies report the ability of flavonoid compounds such as quercetin, myricetin, apigenin, and epigallocatechin gallate (EGCG) to modulate critical signaling pathways, reduce oxidative stress, prevent the accumulation of neurotoxic proteins, and support mitochondrial function. These bioactive molecules have exhibited significant potential in slowing disease progression and preserving neuronal integrity. Their therapeutic application, however, has been limited by their poor bioavailability, low stability, and rapid metabolism.

CONCLUSION: Flavonoids have shown promise as naturally derived agents with multi-targeted activity against neurodegenerative processes. Enhancing their absorption and stability through novel delivery systems and structural modifications could significantly improve their clinical efficacy. When administered early or as a complementary therapy, flavonoids can be considered a safe and effective approach to the management of neurodegenerative diseases.},
}

@article {pmid41245603,
year = {2025},
author = {Almalki, S and Salama, M and Taylor, MJ and Ahmed, Z and Tuxworth, RI},
title = {FUS-related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review.},
journal = {Frontiers in molecular neuroscience},
volume = {18},
number = {},
pages = {1671910},
doi = {10.3389/fnmol.2025.1671910},
pmid = {41245603},
issn = {1662-5099},
abstract = {Mutations in Fused in Sarcoma (FUS) are associated with neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This systematic review examined the connections between DNA damage in the central nervous system (CNS), dysfunction of DNA repair processes and the FUS proteinopathy. Twelve peer-reviewed publications were analyzed, investigating this question across a range of models, including immortalized cell lines, ALS-FTD patient-derived induced pluripotent stem cells, mouse tissues and post-mortem samples from ALS-FTD patients. The studies also explored the impact of inducing DNA damage using several agents, including calicheamicin and etoposide, on FUS pathology. Our findings indicated that accumulated DNA damage was documented in all twelve studies, with a key finding being the disruption of interactions between FUS and the DNA damage response (DDR). FUS interactions with various DDR and DNA repair proteins involved in sensing DNA damage and executing the major repair pathways were impaired, resulting in elevated levels of DNA damage in both the nucleus and mitochondria. Therefore, FUS is an essential protein for the preservation of genomic integrity and this loss of genome stability is likely to be a key contributor to the neurodegeneration in ALS-FTD.},
}

@article {pmid41239797,
year = {2025},
author = {Garg, N and Dhankhar, S and Dhariya, A and Parkash, C and Chauhan, S and Singh, TG},
title = {Role of Liposomes in the Treatment of Neurodegenerative Disorders: A Comprehensive Review.},
journal = {Central nervous system agents in medicinal chemistry},
volume = {25},
number = {4},
pages = {496-512},
pmid = {41239797},
issn = {1875-6166},
mesh = {Humans ; *Liposomes/metabolism/chemistry ; *Neurodegenerative Diseases/drug therapy/metabolism ; Animals ; *Drug Delivery Systems/methods ; *Neuroprotective Agents/administration & dosage/therapeutic use ; Blood-Brain Barrier/metabolism/drug effects ; },
abstract = {The complex etiology and limited therapy options of neurodegenerative illnesses pose daunting challenges to modern medicine. Nonetheless, novel treatment approaches have exciting new possibilities because of developments in nanotechnology. Liposomes have garnered a lot of interest as a potential treatment for neurological illnesses due to the fact that they are able to adapt to their role as nanocarriers. This review article discusses various uses of liposomes, including their ability to help treat neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease, as well as their diagnostic and neuroprotective uses. Liposomes allow for the targeted delivery of medicines to specific brain areas with minimal systemic side effects since they encapsulate and carry therapeutic molecules across the blood-brain barrier. Due to the fact that they are biocompatible, have surface features that can be adjusted, and have the ability to co-deliver many drugs, liposomes are excellent candidates for combination therapy and personalized medicine procedures. In spite of this, there is a growing body of research that suggests liposomes could serve as a versatile platform for the improvement of neurodegenerative disease treatment. This is a positive sign for the future results of patients and their quality of life.},
}

Humans
*Liposomes/metabolism/chemistry
*Neurodegenerative Diseases/drug therapy/metabolism
Animals
*Drug Delivery Systems/methods
*Neuroprotective Agents/administration & dosage/therapeutic use
Blood-Brain Barrier/metabolism/drug effects

@article {pmid40972307,
year = {2026},
author = {Singh, S and Mohammed, AS and DeJonge, J and Puskoor, AV and Desai, R and Ghani, MU and Ghantasala, P and Fattal, PG and Sareen, N},
title = {Impact of moderate to severe tricuspid regurgitation on long-term clinical outcomes in heart failure: A systematic review and meta-analysis of 456,353 patients.},
journal = {Heart & lung : the journal of critical care},
volume = {75},
number = {},
pages = {90-97},
doi = {10.1016/j.hrtlng.2025.09.015},
pmid = {40972307},
issn = {1527-3288},
mesh = {Humans ; *Tricuspid Valve Insufficiency/complications/mortality/physiopathology ; *Heart Failure/mortality/complications/physiopathology ; Severity of Illness Index ; Global Health ; Hospitalization/statistics & numerical data ; Time Factors ; },
abstract = {INTRODUCTION: Tricuspid regurgitation (TR) may have detrimental effects on heart failure (HF) patients clinically. We aimed to study the impact of severity of TR on the long-term outcomes in patients with HF.

OBJECTIVES: To understand the association between moderate-to-severe TR and long-term clinical outcomes, including mortality and HF-related hospitalizations, in adults with HF.

METHODS: We screened PubMed, SCOPUS, and Google Scholar databases up to May 2024 using appropriate keywords. Pooled odds ratios (OR) and confidence intervals (95 % CI) were estimated using a binary random effects model. Heterogeneity was assessed using I2 statistics, and a leave-one-out analysis was performed.

RESULTS: Ten studies with 456,353 HF patients were included. The mean age was 71.2 years. Severe TR showed a significant association with higher odds of 1-year mortality (OR=1.25 [1.02-1.52], p = 0.03; I2=78.15 %), 2-year mortality (OR=1.63 [1.28-2.09], p < 0.01; I2=0 %), HF hospitalization (OR=1.39 [1.14-1.71], p < 0.01; I2=61.58 %), and composite events (OR=1.44 [1.10-1.88], p < 0.01; I2=73.46 %). However, it showed no association with cardiovascular deaths (OR=1.35 [0.82-2.24], p = 0.24; I2=78.31 %). Upon performing a leave-one-out sensitivity analysis, we found that excluding Adamo et al.'s 2024 study changed the overall OR to 1.34 (95 % CI: 1.29, 1.39), indicating its influence on the estimate.

CONCLUSION: Severe TR is associated with a higher risk of 1-year and 2-year mortality, HF hospitalizations, and composite events among HF patients. Therefore, HF patients with comorbid TR should be promptly screened and managed [Figure 1].},
}

Humans
*Tricuspid Valve Insufficiency/complications/mortality/physiopathology
*Heart Failure/mortality/complications/physiopathology
Severity of Illness Index
Global Health
Hospitalization/statistics & numerical data
Time Factors

@article {pmid41239791,
year = {2025},
author = {Bassi, P and Rana, S and Sapra, V and Raina, A and Kumar, P and Devi, S},
title = {Exploring Novel Therapeutic Avenues: Drug Repurposing for Neurodegenerative Movement Disorders.},
journal = {Current drug research reviews},
volume = {17},
number = {3},
pages = {375-393},
pmid = {41239791},
issn = {2589-9783},
mesh = {Humans ; *Drug Repositioning/methods ; *Neurodegenerative Diseases/drug therapy ; Animals ; *Movement Disorders/drug therapy ; },
abstract = {Neurodegenerative movement disorders, encompassing conditions such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, represent a significant burden on individuals, families, and healthcare systems globally. Traditional drug discovery approaches for these disorders have encountered challenges, including high costs and lengthy timelines. Drug repurposing has emerged in recent years as a promising approach to expedite the discovery of new treatments by leveraging existing drugs approved for other indications. This review explores the landscape of drug repurposed for neurodegenerative movement disorders, highlighting promising candidates, underlying mechanisms, and clinical implications. The rationale behind repurposing, including the advantages of utilizing existing pharmacological agents with established safety profiles and known pharmacokinetics, along with techniques utilized for repurposing (computational and experimental), have been elaborated. Several studies on the potential of pre-existing drugs such as isradipine, tetracycline, ambroxol, metformin, deferiprone, simvastatin, etc., which have been repurposed for neurodegenerative movement disorders, including Parkinson's disease, Huntington's disease, Alzheimer's disease, Multiple Sclerosis, etc. have been discussed. Further, the current scenario and future prospective of drug repurposing have also been touched upon.},
}

Humans
*Drug Repositioning/methods
*Neurodegenerative Diseases/drug therapy
Animals
*Movement Disorders/drug therapy

@article {pmid41238318,
year = {2025},
author = {Soriani, MH and Blasco, H and Corcia, P and Danel-Brunaud, V and Desmaison, A and Pradat, PF and Querin, G and Vourch, P and Guy, N},
title = {Markers of presymptomatic amyotrophic lateral sclerosis: State of the art, practical implications and perspectives.},
journal = {Revue neurologique},
volume = {181},
number = {9},
pages = {893-908},
doi = {10.1016/j.neurol.2025.07.008},
pmid = {41238318},
issn = {0035-3787},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy/blood ; *Biomarkers/analysis/blood ; C9orf72 Protein/genetics ; Superoxide Dismutase-1/genetics ; Mutation ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an identified genetic origin in 10-15% of cases, mainly involving C9orf72 and SOD1 mutations. The increasing number of genetically confirmed ALS cases has led to a growing identification of asymptomatic mutation carriers. While riluzole remains the standard treatment, mutation-specific therapies such as tofersen, that was recently approved in SOD1-ALS, are emerging. In this context, the identification of presymptomatic biomarkers is crucial for monitoring genetically at-risk individuals. Plasma neurofilament light chain can increase up to 3.5years before symptom onset in C9orf72 carriers. Metabolic and neuroimaging alterations together with cognitive or behavioral changes, that are sometimes detectable decades prior to diagnosis, have also been observed. These biomarkers may support early surveillance and intervention strategies. The present review provides an overview of current evidence on presymptomatic biomarkers in ALS mutation carriers and their potential role in genetic counseling, monitoring, and early therapeutic decisions.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/genetics/therapy/blood
*Biomarkers/analysis/blood
C9orf72 Protein/genetics
Superoxide Dismutase-1/genetics
Mutation

@article {pmid38879765,
year = {2025},
author = {Sharma, A and Kakkar, A and Khanna, M and Devi, S},
title = {Arbutin's Potential in Neuroprotection: A Promising Role in Mitigating Neurodegenerative Diseases.},
journal = {Current drug research reviews},
volume = {17},
number = {3},
pages = {343-351},
pmid = {38879765},
issn = {2589-9783},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Neuroprotective Agents/pharmacology/therapeutic use/pharmacokinetics ; *Arbutin/pharmacology/therapeutic use/pharmacokinetics ; Animals ; Oxidative Stress/drug effects ; Blood-Brain Barrier/metabolism ; Neuroprotection/drug effects ; },
abstract = {Naturally occurring glycosylated hydroquinone Arbutin, has drawn interest due to its possible function in reducing the risk of neurodegenerative diseases such as Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. Arbutin is well-known for its anti-inflammatory and antioxidant properties, which are essential in preventing oxidative stress and neuroinflammation. Research has shown that arbutin might alter important physiological pathways connected to protein misfolding, synapse function, and neuronal survival processes linked to the development of neurodegenerative diseases. Arbutin can also penetrate the blood- -brain barrier, which increases its therapeutic potential. Arbutin's neuroprotective properties and promise as a therapeutic agent for neurodegenerative illnesses are summarized in this review, which also emphasizes the need for further study into the molecular processes behind these effects.},
}

Humans
*Neurodegenerative Diseases/drug therapy
*Neuroprotective Agents/pharmacology/therapeutic use/pharmacokinetics
*Arbutin/pharmacology/therapeutic use/pharmacokinetics
Animals
Oxidative Stress/drug effects
Blood-Brain Barrier/metabolism
Neuroprotection/drug effects

@article {pmid41238313,
year = {2025},
author = {Rival, M and Thouvenot, E},
title = {Tracing Neurological Diseases in the presymptomatic phase: moving forward a detection panel.},
journal = {Revue neurologique},
volume = {181},
number = {9},
pages = {821-828},
doi = {10.1016/j.neurol.2025.08.004},
pmid = {41238313},
issn = {0035-3787},
mesh = {Humans ; Biomarkers/analysis ; *Nervous System Diseases/diagnosis ; Neurodegenerative Diseases/diagnosis ; Early Diagnosis ; Disease Progression ; *Prodromal Symptoms ; Asymptomatic Diseases ; },
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) often exhibit a prolonged presymptomatic phase during which neuropathological changes silently progress. Recent advances in biomarker research have revealed molecular and imaging signatures that precede clinical onset by years, offering a critical window for early intervention. This review synthesizes current knowledge on the most promising presymptomatic biomarkers across these conditions, highlighting their biological origins, diagnostic performance, and clinical utility. Particular emphasis is placed on the development and validation of biomarker panels, which combine multiple markers to enhance diagnostic sensitivity and specificity, enabling more accurate detection of disease in its earliest stages. Minimally invasive approaches, such as blood-based assays, are also discussed for their potential to facilitate widespread screening and longitudinal monitoring. As these biomarkers begin to integrate into clinical workflows, particularly in AD and MS, international collaboration will be essential to standardize methodologies and ensure equitable implementation. Ultimately, presymptomatic biomarkers hold transformative potential for shifting neurology toward a proactive and precision-based paradigm.},
}

Humans
Biomarkers/analysis
*Nervous System Diseases/diagnosis
Neurodegenerative Diseases/diagnosis
Early Diagnosis
Disease Progression
*Prodromal Symptoms
Asymptomatic Diseases

@article {pmid41238191,
year = {2025},
author = {Yang, Y and Wang, Q and Wang, Z and Wang, Y and Liu, B and Zhang, Y and Mao, X and Sun, H},
title = {The Role of Fatty Acids in Neurodegenerative Diseases: Mechanistic Insights and Therapeutic Strategies.},
journal = {Journal of lipid research},
volume = {},
number = {},
pages = {100944},
doi = {10.1016/j.jlr.2025.100944},
pmid = {41238191},
issn = {1539-7262},
abstract = {Fatty acids (FAs) play multifaceted roles in neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). This review systematically summarizes current understanding of fatty acid metabolism and its diverse implications in NDD pathology. Short-chain fatty acids (SCFAs), primarily generated by gut microbiota, regulate neuroinflammation, gut-brain communication, and blood-brain barrier (BBB) integrity via epigenetic modifications and immune modulation. Medium-chain fatty acids (MCFAs) exhibit therapeutic potential by improving energy metabolism and neuromuscular function, particularly in ALS models. Long-chain polyunsaturated fatty acids (PUFAs), notably docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), contribute to neuronal membrane integrity, synaptic plasticity, and antioxidant defense, mitigating oxidative stress and neuroinflammation. Conversely, saturated and certain n-6 fatty acids may exacerbate neurodegeneration through pro-inflammatory and oxidative pathways. Emerging evidence highlights fatty acid involvement in key pathological processes such as lipid peroxidation, mitochondrial dysfunction, ferroptosis, and BBB disruption. Therapeutically, targeted supplementation, dietary modification, microbiome manipulation, and advanced nanotechnology-based delivery systems are promising strategies. Nevertheless, precise therapeutic efficacy depends critically on disease stage, dosage, genetic background, and individual metabolic context. Integrating personalized medicine with precision nutritional strategies and novel drug-delivery platforms offers promising avenues to translate fatty acid-based interventions into clinical practice, potentially improving patient outcomes in the aging global population.},
}

@article {pmid41238102,
year = {2025},
author = {Long, J and Liu, S and Shi, Y and Zhang, C and Qin, L and Ai, Q},
title = {Targeting lipid metabolism in neurodegenerative diseases: From experimental to clinical.},
journal = {Metabolism: clinical and experimental},
volume = {},
number = {},
pages = {156436},
doi = {10.1016/j.metabol.2025.156436},
pmid = {41238102},
issn = {1532-8600},
abstract = {The human brain, despite accounting for only 2 % of total body weight, exhibits an exceptionally high lipid content (approximately 20 % of its mass), highlighting the critical role of lipid metabolism in maintaining neural homeostasis and function. Neurodegenerative diseases-including Alzheimer's disease (AD), Parkinson's disease (PD), stroke, Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)-are characterized by progressive neuronal dysfunction and myelin degeneration. These conditions predominantly affect aging populations and represent a growing global health challenge. While aging remains the primary risk factor, compelling evidence now underscores the involvement of dysregulated lipid metabolism in their pathogenesis. However, the precise mechanisms linking dynamic lipid metabolic alterations to disease progression remain incompletely elucidated. This review systematically examines the multifaceted contributions of lipid metabolism to neurodegenerative processes and critically assesses emerging therapeutic strategies that target lipid pathways for the treatment of neurodegenerative disorders.},
}

@article {pmid41234489,
year = {2025},
author = {Chan, JM and Romano, C and Lee, AY and Wang, S and Lombardo, D and Kamdar, F and Dora, M and Khan, S and Mammen, P and Kimonis, V},
title = {Cardiomyopathy in valosin-containing protein multisystem proteinopathy: Evaluation, diagnosis, and management.},
journal = {American heart journal plus : cardiology research and practice},
volume = {60},
number = {},
pages = {100644},
pmid = {41234489},
issn = {2666-6022},
abstract = {Valosin-containing protein (VCP)-associated multisystem proteinopathy is a rare, autosomal dominant disease that affects skeletal muscle, bone, central nervous system, and the heart. While VCP mutations are well established as causing inclusion body myopathy, Paget's disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis, their role in cardiomyopathy remains underrecognized. This review aims to evaluate the pathophysiology, diagnostic approach, and management of VCP-associated cardiomyopathy to provide a framework for clinical care and future research. Emerging evidence from animal models and human case studies suggests that VCP dysfunction disrupts cardiomyocyte homeostasis, impairs protein degradation, and alters mitochondrial function, leading to maladaptive cardiac remodeling and susceptibility to dilated or hypertrophic cardiomyopathy. Echocardiographic studies in patients with VCP variants reveal a significant prevalence of diastolic dysfunction, conduction abnormalities, and variable degrees of systolic impairment. Despite these findings, there are no standardized guidelines for the diagnosis and management of VCP-associated cardiomyopathy. Current treatment strategies are extrapolated from heart failure guidelines, incorporating neurohormonal blockades with angiotensin-converting enzyme inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. Our review highlights the need for systematic screening protocols, genotype-phenotype correlation studies, and the development of targeted therapies. Future research should focus on identifying biomarkers for early detection, elucidating the molecular mechanisms underlying cardiac dysfunction, and assessing the efficacy of novel treatment strategies. Recognizing VCP-associated cardiomyopathy as a distinct clinical entity will facilitate earlier diagnosis, improve patient outcomes, pave the way for disease-specific therapeutic interventions and insights into the mechanism for isolated cardiomyopathy.},
}

@article {pmid41229731,
year = {2025},
author = {Nasir, AR and Delpirou Nouh, C},
title = {TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and current and prospective biomarkers.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1671419},
pmid = {41229731},
issn = {1662-5102},
abstract = {Though usually described as isolated models, neurodegenerative diseases exist in a significant proportion of cases as mixed pathologies, particularly in older adults. The presence of co-pathologies may influence phenotypes and progression, and the correct classification in vivo has proven to be challenging, particularly without proper biomarker panels. Recent breakthroughs in biomarkers, enabling earlier detection in Alzheimer's disease and, more recently, in synuclein-related diseases, are promising as a first step toward the wider detection of all other abnormal proteins involved in neurodegenerative diseases. Over the past decade, the growing body of research on TDP-43 pathology has led to considering TDP-43 as a potential major contributor to the neurodegenerative process. TDP-43's normal function is essential for neuronal survival and the regulation of RNA processing and cellular stress response; abnormal TDP-43 protein leads to altered cell function and survival. TDP-43 is notably the neuropathological hallmark of amyotrophic lateral sclerosis (ALS) as well as some form of frontotemporolobar degeneration (FTLD). Tauopathies, divided in primary or secondary tauopathies cover other forms of FTLD including Pick disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) but also non-FTLD diseases like Alzheimer's disease (AD) which can be classified as secondary tauopathy. As the importance of copathology is more and more recognized, TDP-43 is also frequently observed in conjunction with other proteinopathies, possibly with a synergistic or additive effect, although the exact mechanism is still unclear. In Alzheimer's disease, the limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) co-occurrence with Alzheimer's disease neuropathologic changes (ADNC) lead to a more rapid course. Although there are currently no approved and validated biomarkers for its early detection, several promising tools, including neuroimaging and biofluid biomarkers, are under development, offering hope for the earlier detection of TDP-43 pathology in vivo. Accurate identification of the underlying proteinopathies and pathological processes could lead to better diagnosis and classification, more precise selection of clinical trial candidates, and ultimately, disease-specific tailored treatments.},
}

@article {pmid41227379,
year = {2025},
author = {Spedding, M},
title = {Does Amyotrophic Lateral Sclerosis (ALS) Have Metabolic Causes from Human Evolution?.},
journal = {Cells},
volume = {14},
number = {21},
pages = {},
doi = {10.3390/cells14211734},
pmid = {41227379},
issn = {2073-4409},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/genetics ; Animals ; *Biological Evolution ; Mixed Function Oxygenases/metabolism/genetics ; },
abstract = {As so many drugs have failed in ALS a new approach is needed. The author proposes that recent human genetic variants may play major roles in the disease, changing metabolism. Evolution of hominins was accelerated 3-2.5 Mya, by cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) becoming a unitary pseudogene after a pathogenic infection, changing the sialome, and hence metabolism, brain development and neuromuscular junctions (NMJs). This was when hominins evolved to run in Africa and develop bigger brains. Deletion of CMAH in mice allows them to run for longer (~50%). The enzyme CMAH is critical for the sialome, particularly the neurotrophin GM1, a critical hub for viral infection and for NMJ stability, but which is lost from NMJs at the beginning of denervation, probably due a 10-fold increase in spinal cord glucosylceramidases (non-lysosomal GBA2). A GBA2 inhibitor, ambroxol, is currently in phase II for ALS. Human-specific GM1 may be critical for human evolution, lactate metabolism and ALS. Lipid/lactate metabolism changed to support these evolutionary changes and lactate is a major body/brain fuel, but compromised in ALS patients and a marker of disease progression. Recent progress in sports science involving lactate metabolism and human performance may also be relevant to ALS therapies, and incidence.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/genetics
Animals
*Biological Evolution
Mixed Function Oxygenases/metabolism/genetics

@article {pmid41226260,
year = {2025},
author = {Cutter, LR and Ren, AR and Banerjee, IA},
title = {Advances in Naturally and Synthetically Derived Bioactive Sesquiterpenes and Their Derivatives: Applications in Targeting Cancer and Neurodegenerative Diseases.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {21},
pages = {},
pmid = {41226260},
issn = {1420-3049},
support = {N/A//Henry Luce Foundation/ ; N/A//Fordham University/ ; },
mesh = {Humans ; *Sesquiterpenes/chemistry/pharmacology/therapeutic use/chemical synthesis ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neoplasms/drug therapy/metabolism ; Animals ; *Biological Products/chemistry/pharmacology/therapeutic use ; *Antineoplastic Agents/pharmacology/chemistry ; Antioxidants/chemistry/pharmacology ; },
abstract = {Sesquiterpenes are a diverse class of natural products that have garnered considerable interest for their potent bioactivity and structural variability. This review highlights advances in the derivatization of various sesquiterpene lactones, quinones, and alcohols, particularly in targeting cancer and neurodegenerative diseases. The structural modifications discussed include the incorporation of triazole, arylidene, or thiol moieties with eudesmane, guaiane, and germacranolide-type sesquiterpenes, among others. In addition, the conjugation with chemotherapeutics, as well as the development of nanoscale therapeutics, is also discussed. Such modifications have expanded the pharmacological potential, enabling improved specificity, cytotoxicity profiles, and sensitization toward tumor cells. Additionally, sesquiterpenes such as parthenolide (20), pterosinsade A (176), and cedrol (186) have demonstrated potential in mitigating neurodegeneration via anti-inflammatory and antioxidant signaling pathway-modulation mechanisms, with potential applications in Alzheimer's, Parkinson's, and ALS diseases. Mechanistic insights into redox signaling modulation, NF-κB inhibition, ROS regulation, and disruption of aggregation underscore their multifaceted modes of action. This review highlights the translational promise of sesquiterpene derivatives as dual-action agents for potential drug development in a plethora of diseases that are caused by inflammation and free-radical damage. It provides a framework for future rational design of multifunctional drug candidates and therapeutics.},
}

Humans
*Sesquiterpenes/chemistry/pharmacology/therapeutic use/chemical synthesis
*Neurodegenerative Diseases/drug therapy/metabolism
*Neoplasms/drug therapy/metabolism
Animals
*Biological Products/chemistry/pharmacology/therapeutic use
*Antineoplastic Agents/pharmacology/chemistry
Antioxidants/chemistry/pharmacology

@article {pmid41224659,
year = {2025},
author = {Moss, KR and Darvishi, FB and Badawi, Y and Fish, LA and Funke, JR and Pedersen, TH and Robitaille, R and Arnold, WD and Burgess, RW and Meriney, SD and Nishimune, H and Saxena, S},
title = {The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {45},
number = {46},
pages = {},
doi = {10.1523/JNEUROSCI.1353-25.2025},
pmid = {41224659},
issn = {1529-2401},
mesh = {Humans ; *Neuromuscular Junction/pathology/physiopathology/physiology ; *Aging/pathology/physiology ; Animals ; *Neuromuscular Diseases/physiopathology/pathology ; Schwann Cells ; },
abstract = {The neuromuscular junction (NMJ) is a specialized synapse essential for effective motor neuron-muscle communication and is increasingly recognized as a vulnerable site in aging and neuromuscular disease. While traditionally considered a final common pathway for motor deficits, accumulating evidence demonstrates that NMJ dysfunction is an early and critical driver of disease onset and progression in conditions such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. This review highlights shared and disease-specific mechanisms contributing to NMJ impairment, including presynaptic, postsynaptic, and perisynaptic Schwann cell defects in these diseases. We also discuss age-related changes at the NMJ, emphasizing its role in sarcopenia and muscle weakness in older adults. Furthermore, we explore emerging molecular drivers of NMJ dysfunction uncovered through studies in congenital myasthenic syndromes, autoimmune disorders, and advanced omics approaches. By integrating insights across diseases and aging, we underscore the potential for shared therapeutic strategies aimed at stabilizing NMJ function. Promising interventions targeting presynaptic neurotransmitter release, postsynaptic excitability, and perisynaptic Schwann cells are discussed as avenues to improve neuromuscular transmission and maintain muscle strength. Finally, we discuss the challenges and opportunities in translating these mechanistic insights into clinical therapies and highlight how novel human neuromuscular organoid models and advanced molecular profiling can bridge this gap. Together, these insights establish the NMJ as a critical, modifiable target for preserving motor function across neuromuscular diseases and aging.},
}

Humans
*Neuromuscular Junction/pathology/physiopathology/physiology
*Aging/pathology/physiology
Animals
*Neuromuscular Diseases/physiopathology/pathology
Schwann Cells

@article {pmid41219095,
year = {2025},
author = {Pu, S and Sawyer, A and Levinson, C and Putrino, D and Kirke, DN},
title = {Exploring Voice Banking as an Alternative Augmentative Communication Strategy for Individuals with Dysphonia, Aphonia, and Dysarthria: A Scoping Review.},
journal = {Journal of voice : official journal of the Voice Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jvoice.2025.10.018},
pmid = {41219095},
issn = {1873-4588},
abstract = {OBJECTIVES: This scoping review sought to: (i) review studies involving people diagnosed with dysphonia, aphonia, and dysarthria who have used voice banking technology in a hospital or community setting, and (ii) understand the scope of research surrounding existing voice banking technology and software in the clinical setting.

METHODS: This scoping review was conducted according to the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews. An electronic search of databases, including Ovid MEDLINE(R), Embase (Ovid), APA PsycINFO (Ovid), and CINAHL was conducted. Title, abstract, and full text screening were completed using Covidence (Veritas Health Innovation, Melbourne, Australia) by two reviewers.

RESULTS: After deduplication, 1336 studies underwent title and abstract screening. Of these, the full texts of 65 studies were reviewed, and 23 were included. Three distinct topics were identified in the search: (i) message banking, in which discrete messages or phrases are recorded for later use, without the ability to create novel phrases outside of those previously recorded; (ii) voice banking, in which all the necessary phonemes in the target language are captured, with the goal of generating a personalized synthetic voice that can generate novel phrases; (iii) and voice conversion or voice reconstruction, in which pathologic voices or speech are "converted" into a personalized synthetic voices.

DISCUSSION AND CONCLUSION: This scoping review summarized the evidence for voice banking technology use in people diagnosed with dysphonia and dysarthria and sought to understand the research landscape of existing types of voice banking technology and software use in a clinical setting. The included papers were highly heterogeneous in terms of the population and type (research vs clinical program vs review/other). There is a pressing need for the publication of clinical programs and models facilitating the adoption of voice banking, especially within populations affected by conditions such as amyotrophic lateral sclerosis and laryngectomy, to address existing gaps and foster broader implementation and accessibility.},
}

@article {pmid40920400,
year = {2025},
author = {Urso, D and Giannoni-Luza, S and Brayne, C and Ray, N and Logroscino, G},
title = {Incidence and Prevalence of Frontotemporal Dementia: A Systematic Review and Meta-Analysis.},
journal = {JAMA neurology},
volume = {82},
number = {11},
pages = {1144-1152},
pmid = {40920400},
issn = {2168-6157},
mesh = {Humans ; *Frontotemporal Dementia/epidemiology ; Incidence ; Prevalence ; },
abstract = {IMPORTANCE: Comprehensive incidence and prevalence rates of frontotemporal dementia are currently not available.

OBJECTIVE: To estimate the incidence and prevalence of frontotemporal dementia and its clinical variants in the overall population and age subgroups.

We systematically searched PubMed, EMBASE, and Scopus between January 1, 1990, and October 22, 2024, for population-based studies estimating the incidence and/or prevalence of FTD.

DATA EXTRACTION AND SYNTHESIS: Studies and data were screened and extracted independently by 2 investigators in accordance with PRISMA guidelines. Incident and prevalent cases together with the population at risk were pooled using random-effects meta-analysis. Differences in heterogeneity by FTD variants and populations at risk were estimated.

MAIN OUTCOMES AND MEASURES: Prevalent and incident cases as numerator were based on well-defined clinical criteria. Denominators were derived either from census population data or from author-defined populations at risk.

RESULTS: From 1854 screened articles, 32 eligible population-based studies were identified. Sixteen were on prevalence and 22 on incidence reporting FTD measures, including those with estimates for the whole population and for specific age subgroups. Pooled crude incidence for FTD was 2.28 (95% CI, 1.55-3.36) per 100 000 person-years and prevalence, 9.17 (95% CI, 3.59-23.42) per 100 000 people. The behavioral-variant FTD pooled crude incidence was 1.20 (95% CI, 0.67-2.16) per 100 000 person-years and prevalence, 9.74 (95% CI, 2.90-32.73) per 100 000 people. The primary progressive aphasia variant pooled crude incidence was 0.52 (95% CI, 0.35-0.79) per 100 000 person-years and prevalence, 3.67 (95% CI, 3.05-4.43). FTD incidence among individuals younger than 65 years was 1.84 (95% CI, 0.79-4.30) per 100 000 person-years and prevalence, 7.47 (95% CI, 4.13-13.49) per 100 000 people. The denominator based on census data showed less heterogeneity than the population at risk defined by the authors (I2: for incidence, 91.6% vs 97.6%, respectively, and for prevalence, 98.8% vs 99.2%, respectively).

CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, estimates indicate that FTD is comparable in frequency to dementia with Lewy bodies and occurs at higher rates than progressive supranuclear palsy, corticobasal syndrome, and amyotrophic lateral sclerosis. These results provide a foundation for future research and public health strategy, especially for underrepresented populations, to better comprehend the global burden of FTD. Our findings provide robust pooled estimates of the incidence and prevalence of FTD and its subtypes, offering a foundation for future research and public health planning.},
}

Humans
*Frontotemporal Dementia/epidemiology
Incidence
Prevalence

@article {pmid40778462,
year = {2025},
author = {Schvey, NA and Tanofsky-Kraff, M},
title = {Commentary on: The Prevalence of Eating Disorders and Disordered Eating in Adults Seeking Obesity Treatment: A Systematic Review With Meta-Analyses by Melville et al.},
journal = {The International journal of eating disorders},
volume = {58},
number = {11},
pages = {2062-2065},
doi = {10.1002/eat.24522},
pmid = {40778462},
issn = {1098-108X},
mesh = {Humans ; *Feeding and Eating Disorders/epidemiology ; *Obesity/therapy/epidemiology ; Prevalence ; Adult ; },
abstract = {Melville et al.'s 2025 systematic review and meta-analysis highlight the prevalence of eating disorders and disordered eating among adults seeking obesity treatment. Findings showed that the prevalence of binge-eating disorder in obesity treatment-seeking samples exceeds community norms. Results corroborate prior research suggesting that high body weight and eating pathology frequently co-occur and that individuals seeking weight management may be a high-risk population for both sub- and full-threshold eating disorders. Although concerns persist that weight loss efforts may promote or worsen eating disorder symptoms, research indicates that structured, evidence-based interventions typically have neutral or positive effects on disordered eating outcomes. However, rigorous and consistent screening for eating disorders among individuals with high weight is lacking. Importantly, obesity and eating disorders share many common etiological factors, suggesting that integrated intervention is both feasible and highly beneficial. Despite this, the fields of obesity and eating disorders remain siloed. This bifurcation disproportionately impacts youth and adolescents who are at high risk for the onset of both conditions. Currently, standards of care fail to include screening for eating disorders, particularly in youth with high weight, who may be overlooked or misdiagnosed due, in part, to weight-based stigma. Universal, developmentally sensitive screening tools and comprehensive assessment of eating disorder risk factors are urgently needed in pediatric primary care settings. As evidence mounts for concurrent treatment models of high weight and eating disorders, integration across science and clinical care is vital to improve outcomes for youth affected by both conditions.},
}

Humans
*Feeding and Eating Disorders/epidemiology
*Obesity/therapy/epidemiology
Prevalence
Adult

@article {pmid41214238,
year = {2025},
author = {Mushtaq, U and Ahmad, B and Khanday, FA and Ahmad, M},
title = {CHI3L1: An Emerging Player in Neuroinflammation and Neurodegeneration.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {23},
pmid = {41214238},
issn = {1559-1182},
abstract = {Neuroinflammation is now being identified as the major factor in the development of various neurological disorders. It is a vital process in neurons and the brain that maintains homeostasis under normal and healthy conditions. However, in hyperactivated states, neuroinflammation can also go awry when microglia and astrocytes enter a toxic, reactive state that can release chemicals that damage neurons. When innate immune cells encounter pathogens, infection, cell debris, or misfolded proteins, they release certain chemokines and cytokines to eliminate the intruding particles and protect the brain. However, persistent inflammatory reactions are harmful and can lead to neurodegeneration by continuously releasing toxic chemicals and proteins. Chitinase-3-like protein 1 (CHI3L1), a secretory protein, is emerging as a key inflammatory molecule that is strongly upregulated during neuroinflammation and has been implicated in the pathogenesis of many diseases. The brain's activated astrocytes are the main source of CHI3L1 and are a dependable biomarker for inflammatory pathologies affecting the central nervous system (CNS), including neurodegeneration and autoimmune diseases. The protein has been implicated in many neurological disorders, including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, and others, mediating neuroinflammation and neurodegeneration. CHI3L1 has contrasting functions in the CNS and other tissues. While the protein promotes cell proliferation and migration in various non-neuronal cancers, at the same time, it simultaneously promotes neurodegeneration and apoptosis in the CNS. This paper reviews the current developments in our knowledge of the pathogenic role of the CHI3L1 protein in various neurological disorders.},
}

@article {pmid41213329,
year = {2025},
author = {Adachi, M and Banno, H and Inoue, H},
title = {Drug discovery research with the iPSC models of neurodegenerative diseases.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {104985},
doi = {10.1016/j.neures.2025.104985},
pmid = {41213329},
issn = {1872-8111},
abstract = {Induced pluripotent stem cells (iPSCs) are widely used in research because they can be used to create models of diseases with the same genomic background as in patients. Recently, it has become recognized that the use of iPSCs for screening can promote drug discovery research. Additionally, research is being conducted to develop high-quality models for drug discovery and to link translational research with clinical studies. The present work focuses on neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), and broadly introduces the latest research using iPSCs, from disease mechanism studies to drug discovery research. In addition, clinical trials based on research with iPSCs have been conducted: bosutinib, ropinirole and ezogabine for ALS, WVE-004 and BIIB078 for ALS with frontotemporal dementia (ALS/FTD), and bromocriptine for familial AD. Finally, we also wish to mention screening studies utilizing artificial intelligence (AI).},
}

@article {pmid41213077,
year = {2025},
author = {Cai, S and Liu, Y and Liu, B and Liao, H and Li, K},
title = {Hexokinase as a Central Hub in Neurodegeneration: From Metabolic Dysfunction to Therapeutic Innovation.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.0891},
pmid = {41213077},
issn = {2152-5250},
abstract = {Neurodegenerative diseases represent an escalating global health crisis affecting more than 55 million people worldwide; however, underlying mechanisms remain unclear, and therapeutic breakthroughs are elusive. Emerging evidence indicates that hexokinase (HK), the rate-limiting glycolytic enzyme, functions as a master regulator orchestrating neuronal survival through metabolic‒mitochondrial coupling. This review consolidates emerging paradigms revealing that HK maintains neuronal viability through its obligate interaction with mitochondrial VDAC1, forming a metabolic checkpoint that integrates energy status with survival signaling. Disease-specific HK dysfunction patterns precede clinical manifestations and drive pathological cascades across primary neurodegenerative conditions. Pathological proteins characteristic of neurodegeneration-amyloid-β in AD, α-synuclein in PD, mutant SOD1 in ALS, and huntingtin in HD-converge to disrupt the HK-VDAC1 axis through distinct molecular mechanisms, triggering mitochondrial permeabilization, bioenergetic collapse, and inflammatory activation. This uncoupling event promotes VDAC1 oligomerization, enabling the cytosolic release of mtDNA, which in turn activates the NLRP3 inflammasome while depleting antioxidant capacity, establishing self-perpetuating neuroinflammatory cycles. The literature reveals that HK functions as a molecular rheostat, determining neuronal fate through glucose-6-phosphate-mediated feedback control, modulation of growth factor signaling, and regulation of apoptosis/survival pathways. Therapeutic targeting of HK through peptide interventions, enzymatic modulation, and gene therapy demonstrates robust neuroprotective effects across multiple disease models. Meanwhile, combination strategies addressing metabolic-inflammatory networks show synergistic efficacy. These insights position HK as a convergent therapeutic nexus offering unprecedented opportunities for precision intervention in neurodegeneration, with potential for early diagnostic applications and preventive strategies that could transform treatment paradigms for conditions affecting millions worldwide.},
}

@article {pmid41212342,
year = {2025},
author = {Zhong, R and Yang, H and Li, X and Wang, F and Zhai, L and Gao, J},
title = {Mitochondria-Mediated Mechanisms of Ferroptosis in Neurological Diseases.},
journal = {Neurochemical research},
volume = {50},
number = {6},
pages = {354},
pmid = {41212342},
issn = {1573-6903},
support = {202403070986//Health Science and Technology Project of Shandong Province/ ; RZ1900011598//post-doctoral foundation of Qingdao University/ ; },
abstract = {Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, is increasingly recognized as a critical contributor to the pathogenesis of various neurological disorders. Mitochondria, the powerhouses of cells, play dual roles as both initiators and mediators of ferroptosis by integrating lipid peroxidation cascades, oxidative stress responses, and iron homeostasis dysregulation. This review first comprehensively explores the multifaceted mechanisms by which mitochondria mediate ferroptosis in neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Friedreich's ataxia (FRDA), amyotrophic lateral sclerosis (ALS), epilepsy, stroke, and brain injury, with a focus on mitochondrial lipid peroxidation and iron metabolism dysregulation. Building on these mechanistic insights, we further discuss emerging evidence suggesting that targeting mitochondrial pathways may represent a promising therapeutic strategy for mitigating ferroptosis-associated neuronal damage. By synthesizing these findings, our review establishes a conceptual foundation for developing innovative neuroprotective interventions through precise modulation of mitochondrial function within ferroptotic pathways.},
}

@article {pmid41207217,
year = {2025},
author = {Wu, Y and Huang, S and Sha, Q and Yu, J},
title = {Emerging and Re-emerging viruses as triggers of human endogenous retrovirus activation: Implications for aging and age-related pathologies.},
journal = {Molecular aspects of medicine},
volume = {106},
number = {},
pages = {101422},
doi = {10.1016/j.mam.2025.101422},
pmid = {41207217},
issn = {1872-9452},
abstract = {The human genome contains a substantial legacy of ancient retroviral infections known as Human Endogenous Retroviruses (HERVs), composing 8 % of our DNA. In healthy young individuals, these elements are kept dormant by robust epigenetic mechanisms, primarily DNA methylation and repressive H3K9me3 histone marks. However, this epigenetic silencing deteriorates with age, leading to the reactivation of HERVs, particularly the youngest HERV-K subfamily. This report posits that this HERV awakening is not a passive byproduct of aging but an active, transmissible driver of pathology. The reactivation of HERVs leads to the production of retrovirus-like particles (RVLPs) that can induce senescence in healthy neighboring cells, propagating a contagious aging phenomenon. Furthermore, the accumulation of HERV-derived dsRNA and reverse-transcribed DNA triggers chronic innate immune responses through pathways including cGAS-STING and IFIH1-MAVS, fueling the systemic, low-grade inflammation characteristic of inflammaging, catalytically accelerated by exogenous viral infections. Pathogens such as SARS-CoV-2, Epstein-Barr Virus (EBV), and Herpes Simplex Virus (HSV-1) can directly transactivate HERVs via their own viral proteins, overwhelming the already compromised epigenetic controls in an aging host. This mechanistic link between viral triggers and endogenous retroviral activity is strongly implicated in a range of age-related diseases, including neurodegenerative disorders such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS), where the HERV-K envelope protein is directly neurotoxic. It is also linked to autoimmune diseases like Multiple Sclerosis and various cancers. This report synthesizes these findings and identifies a novel mechanistic link between viral activity, chronic inflammation, and the onset of age-related diseases.},
}

@article {pmid41205733,
year = {2025},
author = {Hendricus Maes, KJ and Briedé, JJ},
title = {Repurposing immunomodulatory drugs targeting microglia for amyotrophic lateral sclerosis.},
journal = {Brain research},
volume = {},
number = {},
pages = {150032},
doi = {10.1016/j.brainres.2025.150032},
pmid = {41205733},
issn = {1872-6240},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that progressively affects upper and lower motor neurons, leading to symptoms including dysarthria, muscle weakness, and paralysis. The disease is multifactorial, with a variety of contributing pathways, including excitotoxicity, oxidative stress, and neuroinflammation. Current treatments target only two of these pathways with limited efficacy, highlighting the need for alternative approaches. Increasing evidence highlights the involvement of immune dysregulation, particularly microglial-mediated neuroinflammation, in ALS pathology. Fortunately, many immunomodulatory drugs acting on microglia are already available for other diseases, indicating promising opportunities for drug repurposing. This literature review provides an overview of existing drugs under investigation for ALS, including those that have failed, and highlights new microglia-targeting candidates with repurposing potential. Compounds such as ibudilast, fingolimod, and modafinil have shown encouraging initial clinical results, whereas others were well-tolerated but underpowered or failed to demonstrate efficacy. New candidates, such as azithromycin, naltrexone, montelukast, doxycycline, tofacitinib, quercetin, belinostat, and several kinase inhibitors, have demonstrated positive preclinical results, supporting their advancement toward clinical evaluation. Overall, these findings emphasize the potential of microglia-targeting therapies for ALS. To realize this potential, future studies must include larger cohorts, assess effects across disease stages and patient subgroups, and examine sex differences. This is essential to address patient heterogeneity and improve personalized treatment in ALS.},
}

@article {pmid41203507,
year = {2025},
author = {Zhang, YP and Kedia, S and Klenerman, D},
title = {Rethinking neurodegeneration through a co-proteinopathy lens.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2025.10.006},
pmid = {41203507},
issn = {1878-108X},
abstract = {Neurodegenerative diseases have long been considered distinct proteinopathies: amyloid-β and tau in Alzheimer's disease, α-synuclein in Parkinson's disease, and TDP-43 in amyotrophic lateral sclerosis. This single-protein paradigm has guided therapeutic development for decades; yet clinical outcomes remain modest. Mounting evidence, however, reveals that protein aggregates rarely occur in isolation; instead, they coexist, colocalise, and modulate each other's pathogenicity. Here, we propose a co-proteinopathy framework that views neurodegeneration as an interactive network of misfolded proteins rather than as isolated disorders. Adopting this framework demands multiplexed quantification of protein aggregates and disease models that better reflect the biological complexity of human neurodegeneration. The co-proteinopathy perspective offers a more realistic foundation for next-generation approaches to neurodegeneration research and treatment.},
}

@article {pmid41201719,
year = {2025},
author = {Gautam, P and Vishwakarma, RK and Nath, M and Nath, G and Pathak, A},
title = {Microbiota Dysbiosis in Amyotrophic Lateral Sclerosis: A Systematic Review of Human Studies.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {10},
pmid = {41201719},
issn = {1559-1182},
mesh = {*Amyotrophic Lateral Sclerosis/microbiology/complications ; Humans ; *Dysbiosis/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration. Despite intensive research, its pathogenesis remains poorly understood. Recent insights suggest a pivotal role of the gut microbiota in modulating neuroinflammation and neurodegeneration via the gut-brain axis. This systematic review aims to synthesize clinical evidence on gut microbiota dysbiosis in ALS, exploring microbial and metabolic alterations and their associations with disease progression and severity. A comprehensive literature search was conducted across PubMed, Embase, Scopus, Web of Science, and other databases up to May 10, 2024, adhering to PRISMA 2020 guidelines. Eighteen eligible human studies were selected based on predefined inclusion criteria. Data on microbial diversity, taxonomic shifts, metabolite profiles, and clinical correlations were extracted and assessed using a modified Newcastle-Ottawa Scale. Most studies reported altered microbial diversity, reduced butyrate-producing bacteria (e.g., Faecalibacterium, Roseburia), and increased pro-inflammatory taxa (e.g., Escherichia coli, Bacteroides) in ALS. Integrated microbiome-metabolome analyses revealed disruptions in SCFAs, bile acids, and lipid metabolism, some correlating with ALSFRS-R scores and cognitive impairment. Although some studies showed minimal or no differences, the overall evidence supports a link between dysbiosis and ALS pathophysiology. Probiotic trials demonstrated limited efficacy, highlighting the need for targeted, patient-specific interventions. Gut microbiota dysbiosis is increasingly recognized as a contributor to ALS progression. However, methodological variability, small sample sizes, and limited longitudinal data restrict definitive conclusions. Future research should employ standardized, multi-omics approaches and larger cohorts to clarify causal links and develop microbiome-informed diagnostics and therapies for ALS.},
}

*Amyotrophic Lateral Sclerosis/microbiology/complications
Humans
*Dysbiosis/microbiology/complications
*Gastrointestinal Microbiome/physiology

@article {pmid41196032,
year = {2025},
author = {Mansoor, N and Heiman-Patterson, T and Feldman, EL and Wicks, P and Benatar, M and Vieira, F and Glass, J and Levine, T and Bertorini, T and Barkhaus, P and Mascias Cadavid, J and Jackson, C and Jhooty, S and Brown, A and Pattee, G and Sane, H and Mcdermott, CJ and Carter, G and Beauchamp, M and Wang, O and Ratner, D and Bedlack, R and Li, X},
title = {ALSUntangled #81: Pyridostigmine (mestinon[®]).},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2025.2582830},
pmid = {41196032},
issn = {2167-9223},
abstract = {Pyridostigmine (Mestinon[®], Bausch Health, Canada Inc.) increases acetylcholine availability at the neuromuscular junction, enhancing transmission. Preclinical studies suggest that neuromuscular junction dysfunction develops early in ALS, and pyridostigmine may temporarily improve neuromuscular transmission. However, altered neuromuscular junction transmission has uncertain benefits in ALS progression. Pyridostigmine does not have other plausible mechanisms that truly modify ALS pathophysiology. People with ALS (PALS) who have positive acetylcholine receptor autoantibodies and no myasthenia symptoms are unlikely to respond to pyridostigmine treatment. Clinical trials on pyridostigmine in PALS are lacking, but two clinical trials of other similar anticholinesterase agents did not effectively slow ALS progression. Muscarinic cholinergic side effects, including gastrointestinal symptoms, are common. Given the lack of mechanistic plausibility and efficacy, we do not support the use of pyridostigmine for slowing ALS progression.},
}

@article {pmid41194800,
year = {2025},
author = {Su, Z and Xiang, L},
title = {Targeting ER stress in skeletal muscle through physical activity: a strategy for combating neurodegeneration-associated muscle decline.},
journal = {Frontiers in molecular neuroscience},
volume = {18},
number = {},
pages = {1639114},
pmid = {41194800},
issn = {1662-5099},
abstract = {The pathophysiology of neurodegenerative diseases is largely driven by ER stress, contributing to cellular dysfunction and inflammation. Chronic ER stress in skeletal muscle is associated with a deterioration in muscle function, particularly in diseases such as ALS, PD, and AD, which are often accompanied by muscle wasting and weakness. ER stress triggers the UPR, a cellular process designed to restore protein homeostasis, but prolonged or unresolved stress can lead to muscle degeneration. Recent studies indicate that exercise may modulate ER stress, thereby improving muscle health through the enhancement of the adaptive UPR, reducing protein misfolding, and promoting cellular repair mechanisms. This review examines the influence of exercise on the modulation of ER stress in muscle cells, with a particular focus on how physical activity influences key pathways contributed to mitochondrial function, protein folding, and quality control. We discuss how exercise-induced adaptations, including the activation of stress-resilience pathways, antioxidant responses, and autophagy, can help mitigate the negative effects of ER stress in muscle cells. Moreover, we examine the potential therapeutic implications of exercise in neurodegenerative diseases, where it may improve muscle function, reduce muscle wasting, and alleviate symptoms associated with ER stress. By integrating findings from neurobiology, muscle physiology, and cellular stress responses, this article highlights the therapeutic potential of exercise as a strategy to modulate ER stress and improve muscle function in neurodegenerative diseases.},
}

@article {pmid41194479,
year = {2025},
author = {Das, S and Patel, M and Khandelwal, S and Rawat, R and Shukla, S and Kumari, AP and Singh, K and Kumar, A},
title = {From Mutations to Microbes: Investigating the Impact of the Gut Microbiome on Repeat Expansion Disorders.},
journal = {Journal of neurochemistry},
volume = {169},
number = {11},
pages = {e70278},
doi = {10.1111/jnc.70278},
pmid = {41194479},
issn = {1471-4159},
mesh = {*Gastrointestinal Microbiome/physiology/genetics ; Humans ; Animals ; *Mutation/genetics ; Dysbiosis/genetics ; *DNA Repeat Expansion/genetics ; },
abstract = {Repeat expansion disorders (REDs) are a diverse array of genetic disorders characterized by the expansion of specific DNA sequences. These expansions are frequently dynamic and are susceptible to further expansion across generations. They contribute to disease progression by leading symptoms to become more severe and manifest earlier in subsequent generations. Despite a substantial understanding of their molecular mechanisms, the exact etiology of REDs remains tricky. Emerging evidence indicates that gut microbiome dysbiosis significantly impacts REDs by regulating various biochemical pathways. Alterations in microbial diversity and composition have been observed across multiple REDs; however, a comprehensive understanding of the complete scenario remains a significant challenge. To elucidate these dynamic interactions, future research should utilize multifaceted approaches. This review focuses on the key modifications in the gut microbiome that contribute to the pathogenesis of REDs and discusses potential gut microbiome-targeted therapeutic strategies that could be effectively employed to treat these disorders.},
}

*Gastrointestinal Microbiome/physiology/genetics
Humans
Animals
*Mutation/genetics
Dysbiosis/genetics
*DNA Repeat Expansion/genetics

@article {pmid41192771,
year = {2025},
author = {Shima, S and Kondo, T and Inoue, H},
title = {iPSC-derived neural organoids in dementia research: recent advances and future directions.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {104980},
doi = {10.1016/j.neures.2025.104980},
pmid = {41192771},
issn = {1872-8111},
abstract = {Neural organoids are self-assembled three-dimensionally shaped aggregates generated from pluripotent stem cells for the purpose of generating brain-like structures. Organoids derived from patient induced pluripotent stem cells (iPSCs) can recapitulate the features of the disease from molecular to functional levels, which are not fully reproduced by other culture systems or in vivo models. Neural organoids have been applied to model dementia including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis/frontotemporal dementia, and they have recapitulated aspects of their complex pathophysiology, including neuronal network dysfunction and accumulation of pathogenic proteins. Although there are some challenges for the research using neural organoids, including their heterogeneity and the lack of cells of non-neural lineage, researchers have tried to overcome these limitations and have demonstrated their utility in conjugation with gene editing technologies and the assembly system of organoids and specific types of cells. This article reviews current research on iPSC-derived organoids for dementia, discussing both the technical hurdles and the potential for translational applications.},
}

@article {pmid41165282,
year = {2025},
author = {Roedl, K and Genbrugge, C},
title = {Managing cardiac arrest in the intensive care unit.},
journal = {Current opinion in critical care},
volume = {31},
number = {6},
pages = {729-734},
doi = {10.1097/MCC.0000000000001319},
pmid = {41165282},
issn = {1531-7072},
mesh = {Humans ; *Heart Arrest/therapy/epidemiology/etiology/mortality ; *Intensive Care Units ; *COVID-19/epidemiology ; *Cardiopulmonary Resuscitation/methods ; SARS-CoV-2 ; *Critical Care/methods ; },
abstract = {PURPOSE OF REVIEW: This review aims to explore the distinct clinical characteristics, epidemiology, treatment approaches, and research needs concerning cardiac arrest in the intensive care unit (ICU-CA), a specific subset of in-hospital cardiac arrest (IHCA). While IHCA remains a major cause of mortality, recent data indicate improved outcomes, with a notable variation in incidence and survival depending on the location, particularly within the ICU setting.

RECENT FINDINGS: Recent studies underscore that ICU-CA differs significantly from general IHCA in etiology, monitoring, and treatment environment. Although incidence rates vary widely (4-78 per 1000 ICU admissions), recent data suggest a stabilization. Causes of ICU-CA often involve noncardiac factors such as septic shock and respiratory failure. Treatment is typically guided by general advanced life support (ALS) protocols, but ICU-specific resources such as real-time monitoring, invasive pressure measurements, transesophageal echocardiography, and the potential for extracorporeal cardiopulmonary resuscitation offer unique advantages. The COVID-19 pandemic highlighted the vulnerability of ICU patients, with respiratory causes dominating and extremely poor outcomes reported.

SUMMARY: In summary, ICU-CA represents a distinct clinical entity requiring tailored research. Future directions should prioritize international registries, validation of predictive models using artificial intelligence, and clarification of do-not-resuscitate practices to improve outcomes and resource allocation in this critically ill population.},
}

Humans
*Heart Arrest/therapy/epidemiology/etiology/mortality
*Intensive Care Units
*COVID-19/epidemiology
*Cardiopulmonary Resuscitation/methods
SARS-CoV-2
*Critical Care/methods

@article {pmid41191158,
year = {2025},
author = {Pal, B and Panda, S and Bashir, B and Vishwas, S and Chaitanya, M and Hussain, MS and Gupta, G and Kumbhar, P and Gupta, S and Singh, SK},
title = {Nanomedicine-enabled neuroprotection: therapeutic role of berberine in neurodegenerative diseases.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {49},
pmid = {41191158},
issn = {1573-4978},
mesh = {Humans ; *Berberine/therapeutic use/pharmacology ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Nanomedicine/methods ; Animals ; *Neuroprotection/drug effects ; Nanoparticles/chemistry ; Oxidative Stress/drug effects ; Blood-Brain Barrier/metabolism/drug effects ; },
abstract = {Neurodegenerative diseases (NDs), including Alzheimer's, Amyotrophic lateral sclerosis, Huntington's, and Parkinson's, present an increasingly widespread health burden globally with limited curative or treatment modalities, mostly having symptomatic attenuation. Berberine (BBR) is an isoquinoline alkaloid that occurs naturally and has been proposed as a potential neuroprotectant, since it has been found to exert multiple effects to modulate most of the pathological hallmarks of NDs, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and protein aggregation. Although it shows promise, the practical utilization of BBR is marred by low oral bioavailability, high rate of oxidation, and low blood-brain barrier permeability. To combat these issues, recent developments in nanotechnology, especially in the use and creation of lipidic, inorganic, and polymeric nano-particles, have dramatically altered the pharmacokinetics and pharmacodynamics of BBR. This article summarizes recent advances in BBR-based nanoformulations and emphasizes the translational potential of BBR-based nanopreparations to improve treatment response in NDs. It also describes the molecular foundation of the neuroprotective effects of BBR and its possible place in clinical practice. Future nanocarrier development and investigation of BBR mechanisms will be essential to the development of the next generations of therapeutics in NDs.},
}

Humans
*Berberine/therapeutic use/pharmacology
*Neurodegenerative Diseases/drug therapy/metabolism
*Neuroprotective Agents/therapeutic use/pharmacology
*Nanomedicine/methods
Animals
*Neuroprotection/drug effects
Nanoparticles/chemistry
Oxidative Stress/drug effects
Blood-Brain Barrier/metabolism/drug effects

@article {pmid41190025,
year = {2025},
author = {Alhassan, HH and Janiyani, K and Surti, M and Adnan, M and Patel, M},
title = {The dual role of glycogen synthase kinase-3 beta (GSK3β) in neurodegenerative pathologies: interplay between autophagy and disease progression.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1693805},
pmid = {41190025},
issn = {1663-9812},
abstract = {Glycogen Synthase Kinase-3 Beta (GSK3β), a multifunctional serine/threonine kinase, plays a central role in cellular signaling pathways and autophagy regulation, processes critical to neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis (ALS). Dysregulation of autophagy leads to the toxic accumulation of misfolded proteins and damaged organelles, contributing to neuronal loss in these disorders. This review explores the mechanistic interplay between GSK3β and autophagy, highlighting its modulation through key pathways, including mTOR, AMPK and Bcl-2 and its direct impact on autophagy-related proteins such as Beclin-1 and LC3. This review systematically discusses the disease-specific roles of GSK3β in autophagy dysregulation and protein aggregation, providing evidence from recent studies on neurodegenerative models. Additionally, therapeutic approaches targeting GSK3β are evaluated, including preclinical and clinical trials of GSK3β inhibitors and combination therapies with autophagy modulators, emphasizing their potential for improving neuroprotection and cellular homeostasis. Despite its promise, challenges such as off-target effects and pathway complexity remain significant. This review highlights the importance of GSK3β as both a therapeutic target and a biomarker, offering avenues for future research into selective GSK3β modulators that enhance autophagy and mitigate ND progression.},
}

@article {pmid41189652,
year = {2025},
author = {Guo, H and Yang, Z and Zhang, G and Lv, L and Zhao, X},
title = {Meta analysis of the diagnostic efficacy of transformer-based multimodal fusion deep learning models in early Alzheimer's disease.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1641548},
pmid = {41189652},
issn = {1664-2295},
abstract = {INTRODUCTION: This study aims to systematically evaluate the diagnostic efficacy of Transformer-based multimodal fusion deep learning models in early Alzheimer's disease (AD) through a Meta-analysis, providing a scientific basis for clinical applications.

METHODS: Following PRISMA guidelines, databases such as PubMed and Web of Science were searched, and 20 eligible clinical studies (2022-2025) involving 12,897 participants were included. Study quality was assessed using the modified QUADAS-2 tool, statistical analyses were performed with Stata 16.0, effect sizes were pooled via random-effects models, and subgroup analyses, sensitivity analyses, and publication bias tests were conducted.

RESULTS: Results showed that Transformer-based multimodal fusion models exhibited excellent overall diagnostic performance, with a pooled AUC of 0.924 (95% CI: 0.912-0.936), sensitivity of 0.887 (0.865-0.904), specificity of 0.892 (0.871-0.910), and accuracy of 0.879 (0.858-0.897), significantly outperforming traditional single-modality methods. Subgroup analyses revealed that: Three or more modalities achieved a higher AUC (0.935 vs. 0.908 for two modalities, p =0.012). Intermediate fusion strategies (feature-level, AUC=0.931) significantly outperformed early (0.905) and late (0.912) fusion (p <0.05 for both). Multicenter data improved AUC (0.930 vs. 0.918 for single-center, p =0.046), while sample size stratification (<200 vs. ≥200 cases) showed no significant difference (p =0.113). Hybrid Transformer models (Transformer +CNN) trended toward higher AUC (0.928 vs. pure Transformer 0.917, p =0.068) but did not reach statistical significance.

DISCUSSION: Notable studies included Khan et al.'s (2024) Dual-3DM[3]AD model (AUC=0.945 for AD vs. MCI) and Gao et al.'s (2023) generative network (AUC=0.912 under data loss), validating model robustness and feature complementarity. Sensitivity analysis confirmed stable results (AUC range: 0.920-0.928), and Egger's test (p =0.217) and funnel plot symmetry indicated no significant publication bias. Limitations included a high proportion of single-center data and insufficient model interpretability. Future research should focus on multicenter data integration, interpretable module development, and lightweight design to facilitate clinical translation. Transformer-based multimodal fusion models demonstrate exceptional efficacy in early AD diagnosis, with multimodal integration, feature-level fusion, and multicenter data application as key advantages. They hold promise as core tools for AD "early diagnosis and treatment" but require further optimization for cross-cohort generalization and clinical interpretability.},
}

@article {pmid41187881,
year = {2025},
author = {Ge, TQ and Wang, P and Guan, PP},
title = {Targeting the C5-C5aR1 axis: A promising therapeutic strategy for Alzheimer's disease and amyotrophic lateral sclerosis by unlocking neuroprotection.},
journal = {Biochemical pharmacology},
volume = {243},
number = {Pt 1},
pages = {117518},
doi = {10.1016/j.bcp.2025.117518},
pmid = {41187881},
issn = {1873-2968},
abstract = {C5aR1 is a G protein-coupled receptor (GPCR) which is involved in exacerbating neurodegenerative diseases, including Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS). This review highlights the critical role of the C5-C5aR1 axis, in the pathogenesis of neurodegenerative diseases such as AD and ALS. In AD and ALS, abnormal protein aggregates activate the complement system (CS), leading to increased production of C5a. C5a activates C5aR1 on microglia, triggering the release of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) that induce synaptic loss. Concurrently, the C5-C5aR1 axis impairs microglial phagocytic capacity, promoting damage-associated molecular patterns (DAMPs) accumulation and forming a vicious cycle of inflammation and complement activation. Additionally, excessive complement molecule assembles into the terminal complement complex (TCC), which exerts direct neurotoxic effects and drives neuronal apoptosis. Preclinical studies show that C5aR1 antagonists, such as PMX205, mitigate disease progression in AD and ALS animal models by reducing neuroinflammation and preserving synaptic function. These findings underscore the C5-C5aR1 axis as a promising target for neurodegenerative disease therapy and highlight the need for further development of potential antagonists of C5aR1.},
}

@article {pmid41117139,
year = {2025},
author = {Pedro, KM and Alvi, MA and Goulart, GR and Fehlings, MG},
title = {Riluzole as a pharmacological therapy for spinal cord injury: where does this therapy stand?.},
journal = {Current opinion in neurology},
volume = {38},
number = {6},
pages = {625-634},
doi = {10.1097/WCO.0000000000001434},
pmid = {41117139},
issn = {1473-6551},
mesh = {*Riluzole/therapeutic use/pharmacology ; Humans ; *Spinal Cord Injuries/drug therapy ; *Neuroprotective Agents/therapeutic use/pharmacology ; Animals ; },
abstract = {PURPOSE OF REVIEW: Spinal cord injury (SCI) remains a disabling condition associated with long term neurological impairment, functional disability, and reduced quality of life. Despite decades of research, pharmacological interventions with proven clinical efficacy remain limited. This review critically evaluates the current evidence supporting riluzole as a neuroprotective agent for acute traumatic and nontraumatic SCI. We synthesize findings from preclinical and clinical studies, assess the progress towards clinical translation, and outline key challenges and research opportunities for future implementation.

RECENT FINDINGS: Riluzole, an FDA-approved agent for amyotrophic lateral sclerosis (ALS), inhibits voltage-gated sodium channels and modulates glutaminergic transmission, two mechanisms central to the pathogenesis of secondary injury in SCI and in nerve cell degeneration in nontraumatic forms of SCI, including degenerative cervical myelopathy (DCM). Preclinical studies consistently demonstrate functional and histopathological improvements following riluzole administration. Phase I/II trials have provided evidence for its safety and tolerability in acute SCI patients, while the RISCIS and CSM-PROTECT trials, two landmark multicenter randomized controlled studies, along with their secondary analyses, revealed promising multidomain improvements in motor function, independence, and quality of life indices. Sub-studies have also established pharmacokinetic and pharmacodynamic frameworks for individualized dosing, and early biomarker analysis suggests potential for predictive stratification.

SUMMARY: Riluzole represents a promising candidate for neuroprotection in traumatic and nontraumatic SCI. The consistency of favorable trends across multiple domains and strong support from preclinical studies highlight riluzole's value in orphan diseases such as SCI. Future directions should focus on refining the therapeutic window, optimizing PK/PD modeling, and identifying patient subgroups most likely to benefit. Its implementation in a multimodal treatment paradigm for acute SCI will be crucial for optimizing management protocols in this highly disabling condition.},
}

*Riluzole/therapeutic use/pharmacology
Humans
*Spinal Cord Injuries/drug therapy
*Neuroprotective Agents/therapeutic use/pharmacology
Animals

@article {pmid40960157,
year = {2025},
author = {Wang, J and Dai, L and Zhang, Z},
title = {Protein aggregation in neurodegenerative diseases.},
journal = {Chinese medical journal},
volume = {138},
number = {21},
pages = {2753-2768},
pmid = {40960157},
issn = {2542-5641},
mesh = {Humans ; *Neurodegenerative Diseases/metabolism ; alpha-Synuclein/metabolism ; Amyloid beta-Peptides/metabolism ; tau Proteins/metabolism ; *Protein Aggregation, Pathological/metabolism ; DNA-Binding Proteins/metabolism ; Animals ; *Protein Aggregates/physiology ; },
abstract = {Neurodegenerative diseases constitute a group of chronic disorders characterized by the progressive loss of neurons. Major neurodegenerative conditions include Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Pathologically, these diseases are marked by the accumulation of aggregates formed by pathological proteins such as amyloid-β, tau, α-synuclein, and TAR DNA-binding protein 43. These proteins assemble into amyloid fibrils that undergo prion-like propagation and dissemination, ultimately inducing neurodegeneration. Understanding the biology of these protein aggregates is fundamental to elucidating the pathophysiology of neurodegenerative disorders. In this review, we summarize the molecular mechanisms underlying the aggregation and transmission of pathological proteins, the processes through which these protein aggregates trigger neurodegeneration, and the interactions between different pathological proteins. We also provide an overview of the current diagnostic approaches and therapeutic strategies targeting pathological protein aggregates.},
}

Humans
*Neurodegenerative Diseases/metabolism
alpha-Synuclein/metabolism
Amyloid beta-Peptides/metabolism
tau Proteins/metabolism
*Protein Aggregation, Pathological/metabolism
DNA-Binding Proteins/metabolism
Animals
*Protein Aggregates/physiology

@article {pmid40794569,
year = {2025},
author = {Benatar, M and Staffaroni, AM and Wuu, J and McDermott, MP and Quintana, M and Swidler, J and Andersen, G and Huey, ED and Turner, MR and Macklin, EA and Berry, JD and McMillan, CT and Gendron, T and Onyike, C and Rosen, H and Heuer, HW and Grignon, AL and Dave, KD and Balas, C and Gleixner, A and Satlin, A and Dunn, B and Dacks, P and Boxer, AL},
title = {Design considerations for C9orf72 disease prevention trials.},
journal = {Brain : a journal of neurology},
volume = {148},
number = {11},
pages = {3844-3855},
doi = {10.1093/brain/awaf290},
pmid = {40794569},
issn = {1460-2156},
support = {//Association for Frontotemporal Degeneration/ ; //ALS Association/ ; },
mesh = {Humans ; *C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics/prevention & control ; *Frontotemporal Dementia/genetics/prevention & control ; *Clinical Trials as Topic/methods ; DNA Repeat Expansion/genetics ; Research Design ; },
abstract = {The idea that it might be possible to prevent some forms of amyotrophic lateral sclerosis and frontotemporal dementia has finally come of age. The hexanucleotide repeat expansion in the C9orf72 gene accounts for ∼10% of all amyotrophic lateral sclerosis and 10%-15% of all frontotemporal dementia diagnoses, with the two clinical syndromes co-manifesting in a significant number of patients. As a result, clinically unaffected carriers of pathogenic C9orf72 repeat expansions are currently the largest identifiable population at significantly elevated risk for both amyotrophic lateral sclerosis and frontotemporal dementia, and in whom it might be possible to prevent the emergence of clinically manifest disease. Strategies for the design of disease prevention trials among clinically unaffected C9orf72 carriers have begun to emerge separately in the amyotrophic lateral sclerosis and frontotemporal dementia fields. However, recognition of the need to define neurodegenerative diseases based on biology underscores the need to consider all potential clinical manifestations of a C9orf72 repeat expansion together, rather than the traditional siloed approach of focusing on only amyotrophic lateral sclerosis or only frontotemporal dementia. Indeed, emerging clinical and biological markers that might be used to quantify pre-symptomatic disease progression and to predict the short-term risk of phenoconversion to clinically manifest disease are shared across the phenotypic spectrum. Given the anticipated progress in the development of therapeutic strategies to target the C9orf72 repeat expansion, and the enthusiasm for prevention trials among the unaffected C9orf72 repeat expansion carrier population, now is the time to begin work on the design of disease prevention trials. To this end, The Association for Frontotemporal Degeneration and The ALS Association supported a multi-stakeholder workshop (in Washington D.C., June 2024) to unify efforts to design a prevention trial for the population at elevated genetic risk for the phenotypic spectrum of C9orf72 disease. Here we describe recommendations emanating from this workshop for the selection of outcome measures, delineation of eligibility criteria, optimal use of biomarkers and digital health technologies, potential analytic frameworks and relevant regulatory considerations related to C9orf72 disease prevention trials. We also emphasize the importance of the amyotrophic lateral sclerosis and frontotemporal dementia communities working together in partnership with the C9orf72 repeat expansion carrier community, the regulatory authorities and the broader drug development community.},
}

Humans
*C9orf72 Protein/genetics
*Amyotrophic Lateral Sclerosis/genetics/prevention & control
*Frontotemporal Dementia/genetics/prevention & control
*Clinical Trials as Topic/methods
DNA Repeat Expansion/genetics
Research Design

@article {pmid41186720,
year = {2025},
author = {Aijaz, M and Ahmad, M and Ahmad, S and Afzal, M and Kothiyal, P},
title = {The gut-brain axis: role of gut microbiota in neurological disease pathogenesis and pharmacotherapeutics.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41186720},
issn = {1432-1912},
abstract = {The gut-brain axis is a highly complex, bidirectional communication link between the gut and the central nervous system (CNS), mainly through neural, endocrine, immunological, and metabolic pathways. This review outlines the growing contribution of gut microbiota in the remediation of neurological health and also emphasizes the controlling role of gut microbiota on the synthesis of neurotransmitters. Emerging evidence indicates that dysbiosis of the gut is related to a variety of neurodegenerative and neuropsychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), autism spectrum disorders (ASD), depression, and glioblastoma. Mechanistic understandings show that gut microbes critically contribute to neuroimmune and blood-brain barrier (BBB) signaling. The peripheral association of gut microflora, networked with inflammasome activation, nuclear factor kappa B (NF-κB), and type-I IFN pathways highlights their role in CNS inflammation. Microbiota-targeted interventions with probiotics, prebiotics, synbiotics, antibiotics, dietary modifications, and fecal microbiota transplantation are examined for their therapeutic potential. These strategies appear to be promising to reinstate microbial balance, enhance neuroplastic responses, and ameliorate the disease symptoms. The review highlights personalized microbiome-based algorithms, underpinned by integrated multi-omics technologies and machine-learning-driven diagnostics. Future research should address underlying microbial mechanisms and perform large, randomized controlled trials in order to establish microbiota-based therapies for neurological disorders.},
}

@article {pmid41184709,
year = {2025},
author = {Kiecka, A and Szczepanik, M},
title = {Dietary modulation of the gut microbiome as a supportive strategy in the treatment of amyotrophic lateral sclerosis - a narrative review.},
journal = {Pharmacological reports : PR},
volume = {},
number = {},
pages = {},
pmid = {41184709},
issn = {2299-5684},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease leading to permanent damage to the central and peripheral motor neurons. Currently, there is no effective treatment for ALS, and therapy focuses solely on slowing the progression of the disease. Recent studies show that gut microbiota plays an important role in the development of neurodegenerative diseases. Altered gut microbiota has also been found in ALS. These changes have prompted the search for alternative forms of ALS treatment, focusing on changing the microbial composition of the gut. It has been noted that diet, probiotics, prebiotics and vitamins can all influence the course of ALS. Another interesting issue is fecal microbiota transplantation, which is already used in the treatment of certain intestinal diseases and could potentially be useful in the treatment of ALS. This review summarizes current knowledge on the impact of gut microbiota on the neurodegenerative process in ALS, with particular emphasis on the role of diet and probiotics. It also discusses potential mechanisms and highlights future research directions in this emerging field.},
}

@article {pmid41183377,
year = {2025},
author = {Morris, AC and Seker, A and Telesia, L and Wickersham, A and Ching, BC and Roy, R and Epstein, S and Matcham, F and Sonuga-Barke, E and Downs, J},
title = {Adherence to Actigraphic Devices in Elementary School-Aged Children: Systematic Review and Meta-Analysis.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e79718},
doi = {10.2196/79718},
pmid = {41183377},
issn = {1438-8871},
mesh = {Humans ; Child ; *Actigraphy/instrumentation ; *Patient Compliance/statistics & numerical data ; Child, Preschool ; Female ; Schools ; Male ; },
abstract = {BACKGROUND: Consistent wear is essential for valid and reliable actigraphy data. Adherence to actigraphy may be challenging in primary school children due to developmental and design considerations, yet no quantitative synthesis of adherence in this age group exists.

OBJECTIVE: The aim of this study was to provide the first pooled estimate of actigraphy adherence in primary school-aged children and examine the impact of individual, device, and study-specific factors on adherence.

METHODS: We searched seven electronic databases for studies reporting adherence to actigraphy in primary school-aged children. Searches were conducted in Embase, MEDLINE, PsycINFO, Social Policy and Practice via OVID, Education Resources Information Center, British Education Index, and CINAHL via EBSCO using database-specific search strategies conducted between January 2018 and January 24, 2023. Forward and backward citation searches were completed on the Web of Science Core Collection and Google Scholar. Gray literature searches were undertaken in PsycEXTRA and Healthcare Management Information Consortium. Empirical studies reporting quantitative data on adherence to community-based actigraphy in children aged 5-11 years (or if ≥50% of the average age fell within this range) were included. Eligible studies were written in English and could be published or unpublished. Risk of bias was assessed using an 8-item checklist adapted from Berger et al's actigraphy reporting standards. All included studies were narratively synthesized, and adherence data were pooled in a proportional meta-analysis. Adherence was calculated as the proportion of children meeting wear-time criteria to be included in the analysis compared to the number of children invited to use the device at baseline. Meta-regression was used to examine the impact of individual, device, and study-specific factors on adherence. Prediction intervals were calculated to estimate the range of adherence expected across future studies.

RESULTS: Data were extracted from 235 studies (N=148,161); of these, 135 studies (n=64,541) provided adherence data for proportional meta-analysis. Pooled adherence, measured across 1-140 days, was 81.6% (95% CI 78.7%-84.4%; I2=98.8%). The prediction intervals (42.8%-100%) indicated substantial variability in adherence estimates across studies. Meta-regression suggested that individual characteristics contributed to observed heterogeneity as children with a physical health diagnosis (b=0.236, 95% CI 0.009-0.464; P=.04) and those with neurodevelopmental or mental health diagnosis (b=0.395, 95% CI 0.125-0.665; P=.004) demonstrated higher adherence than undiagnosed children, though these effects were of modest magnitude. No significant effects were found for age, placement, protocol length, protocol deviation, or incentivization. Reporting quality was poor, with only 3.4% of studies satisfying all criteria.

CONCLUSIONS: This review demonstrates generally high actigraphy adherence in primary school-aged children, particularly those with health conditions. However, observed variability indicates that adherence was much lower in some contexts, underscoring that the reported pooled adherence cannot be assumed across future actigraphy applications within this age group. Future research should use standardized adherence reporting and should plan for adherence variability.},
}

Humans
Child
*Actigraphy/instrumentation
*Patient Compliance/statistics & numerical data
Child, Preschool
Female
Schools
Male

@article {pmid41182353,
year = {2025},
author = {Cai, Y and Huang, S and Dong, Y and Li, S and Jin, X},
title = {PIWI-Interacting RNAs in brain health and disease: biogenesis, mechanisms, and therapeutic horizons.},
journal = {Psychopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41182353},
issn = {1432-2072},
support = {81971083//National Natural Science Foundation of China/ ; 25JCLZJC00190//Tianjin Natural Science Foundation Project/ ; },
abstract = {PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs originally identified for their role in transposon silencing in germ cells, have recently been recognized as pivotal regulators of gene expression in the central nervous system. Beyond their canonical functions in genome defense, emerging evidence highlights piRNAs as key modulators of neuronal development, synaptic plasticity, axonal regeneration, and neuroimmune interactions-processes central to brain function and dysfunction. This review provides a comprehensive overview of piRNA biogenesis, molecular mechanisms, and regulatory pathways relevant to neurobiology. We focus on the growing body of evidence implicating piRNA dysregulation in major neurological and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, glioma, autism spectrum disorder, and schizophrenia. Importantly, we discuss the neuropharmacological implications of piRNA pathways as novel targets for therapeutic intervention and their potential utility as biomarkers for early diagnosis and treatment stratification. By integrating mechanistic insights with emerging translational evidence, this review highlights piRNAs as promising molecular targets in the development of next-generation neurotherapeutics aimed at modifying disease progression and improving brain health.},
}

@article {pmid41180593,
year = {2025},
author = {Civita, E and Nicolella, V and Fiorenza, M and Cosimato, V and Castaldo, G and Morra, VB and Moccia, M and Terracciano, D},
title = {Advancing Clinical Use of Neurofilament Light Chain: Translational Insights From Research to Routine Practice.},
journal = {Biomarker insights},
volume = {20},
number = {},
pages = {11772719251364018},
pmid = {41180593},
issn = {1177-2719},
abstract = {Neurofilament Light Chain (NfL) has emerged as a promising biomarker for neurological diseases. NfL, a structural component of axons, is released into cerebrospinal fluid (CSF) and blood following neuro-axonal damage. Highly sensitive immunometric assays have enabled its reliable quantification in blood, facilitating non-invasive monitoring. Several studies demonstrated strong correlations between NfL levels and the risk of developing different neurological diseases and, in individuals already living with a neurological disease, with the risk of worsening. However, interpretation is affected by factors like age, BMI, renal function, and comorbidities. NfL is already utilized as a diagnostic and prognostic biomarker in clinical practice, particularly in specialized centers and research settings, although no FDA-cleared assay is currently available for routine use. Recent research has highlighted that NfL may represent the first of a new generation of neurological biomarkers, with many more ready to come, such as glial fibrillary acidic protein (GFAP), further improving diagnostic and prognostic accuracy. Despite its promising role in the landscape of biomarkers, challenges remain to implement NfL in daily clinical practice, including standardization of assays, defining reference values, and ensuring methodological consistency. Addressing these limitations will be essential for integrating NfL into routine clinical practice, ultimately advancing precision medicine in neurology.},
}

@article {pmid41180498,
year = {2025},
author = {Shamsi, A and Alrouji, M and AlOmeir, O and Tasqeruddin, S and Dinislam, K and Zuberi, A},
title = {CRISPR-Cas9: bridging the gap between aging mechanisms and therapeutic advances in neurodegenerative disorders.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1681891},
pmid = {41180498},
issn = {1662-5102},
abstract = {Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, ALS, and spinocerebellar ataxia are becoming more prevalent as populations age, posing major global health challenges. Despite decades of research, effective treatments that halt or reverse these conditions remain elusive. Aging is the most significant risk factor in the development of these diseases, intertwining with molecular processes like DNA damage, mitochondrial dysfunction, and protein aggregation. Recent advances in gene-editing technologies, particularly CRISPR-Cas9, are beginning to shift the therapeutic landscape. This revolutionary tool allows for precise correction of genetic mutations associated with neurodegeneration, offering the potential for disease modification rather than symptom management alone. In this review, we explore how CRISPR-Cas9 is being leveraged to target key genes implicated in various neurodegenerative conditions and how it may overcome barriers posed by aging biology. We also examine the delivery systems and safety challenges that must be addressed before clinical application. With continued progress, CRISPR-Cas9 could mark a turning point in our ability to treat or even prevent age-related neurological decline.},
}

@article {pmid41179113,
year = {2025},
author = {Luo, Y and Xu, Z and Li, Z},
title = {Advances in Induced Pluripotent Stem Cell Reprogramming and Its Application in Amyotrophic Lateral Sclerosis: A Review.},
journal = {FASEB bioAdvances},
volume = {7},
number = {11},
pages = {e70065},
pmid = {41179113},
issn = {2573-9832},
abstract = {Since Yamanaka's landmark achievement in reprogramming somatic cells into induced pluripotent stem cells (iPSCs) using the four key transcription factors-OCT4, SOX2, KLF4, and c-Myc (OSKM)-iPSC technology has made significant strides. Notable advancements include refining reprogramming factors, delivery systems, somatic cell selection, and optimization of reprogramming conditions, along with developing chemical reprogramming methods. With their unparalleled proliferative capacity and near-pluripotent differentiation potential, iPSCs have become invaluable tools for investigating neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Neuronal models derived from ALS patient-specific iPSCs, particularly iPSC-derived motor neurons (iPSC-MNs), offer a robust platform to recapitulate disease-specific pathology and investigate the molecular mechanisms underpinning ALS, thereby accelerating the discovery of novel therapeutic strategies. This review highlights the evolution of iPSC technology and its transformative applications in ALS modeling, drug discovery, and therapeutic development.},
}