@article {pmid40955309,
year = {2025},
author = {Wang, L and Feng, L and Ning, B and Wang, Z and Dai, C and Li, M},
title = {Natural Products from Chinese Medicine Targeting NF-κB Signaling: Emerging Therapeutic Avenues for Neurodegenerative Diseases.},
journal = {Drug design, development and therapy},
volume = {19},
number = {},
pages = {8135-8159},
pmid = {40955309},
issn = {1177-8881},
mesh = {Humans ; *NF-kappa B/metabolism/antagonists & inhibitors ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Biological Products/pharmacology/chemistry ; *Medicine, Chinese Traditional ; Signal Transduction/drug effects ; Animals ; *Drugs, Chinese Herbal/pharmacology/chemistry ; },
abstract = {This review summarizes recent advances in leveraging natural products from Chinese medicine to modulate the nuclear factor kappa B (NF-κB) signaling pathway for the prevention and treatment of neurodegenerative diseases (NDDs), focusing specifically on Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). NF-κB proteins regulate cellular biological activity by binding to promoter regions in the nucleus and transcribing various protein-coding genes. Emerging evidence indicates that NF-κB plays a pivotal role in driving key hallmarks of NDD progression, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and dysregulation of the cell cycle. Natural products from Chinese medicine exert modulatory effects on NF-κB signaling through diverse pharmacological mechanisms, ultimately improving cognitive and motor impairments in preclinical NDDs models. The pleiotropic nature of natural products derived from traditional Chinese medicine (TCM)-which operate through subunit-specific modulation of NF-κB-underscores their potential as next-generation therapeutics. Investigating the intricate regulation of NF-κB by natural products from Chinese medicine will not only enrich our understanding of the pathogenesis of NDDs but also establish a theoretical foundation for the development of new therapeutic drugs for NDDs, providing innovative strategies for prevention and treatment.},
}

Humans
*NF-kappa B/metabolism/antagonists & inhibitors
*Neurodegenerative Diseases/drug therapy/metabolism
*Biological Products/pharmacology/chemistry
*Medicine, Chinese Traditional
Signal Transduction/drug effects
Animals
*Drugs, Chinese Herbal/pharmacology/chemistry

@article {pmid40952592,
year = {2025},
author = {Chen, C and Wang, GQ and Li, DD and Zhang, F},
title = {Microbiota-gut-brain axis in neurodegenerative diseases: molecular mechanisms and therapeutic targets.},
journal = {Molecular biomedicine},
volume = {6},
number = {1},
pages = {64},
pmid = {40952592},
issn = {2662-8651},
support = {No. 82160690//National Natural Science Foundation of China/ ; No. ZK [2021]-014//Science and Technology Foundation of Guizhou Province/ ; No. 2020-39//Collaborative Innovation Center of Chinese Ministry of Education/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/therapy/microbiology/metabolism/etiology ; *Gastrointestinal Microbiome ; *Brain/metabolism ; Animals ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; },
abstract = {The microbiota-gut-brain axis (MGBA) is an intricate bidirectional communication network that links intestinal microbiota with the central nervous system (CNS) through immune, neural, endocrine, and metabolic pathways. Emerging evidence suggests that dysregulation of the MGBA plays pivotal roles in the onset and progression of neurodegenerative diseases. This review outlines the key molecular mechanisms by which gut microbes modulate neuroinflammation, blood-brain barrier integrity, protein misfolding, and neuronal homeostasis. We discuss how microbial metabolites, such as short-chain fatty acids, tryptophan derivatives, and bile acids, interact with host to influence CNS functions. Disease-specific features are described across Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis, emphasizing the distinct and overlapping pathways through which gut dysbiosis may contribute to pathogenesis. We further explore the translational potential of microbiota-targeted therapies, including probiotics, fecal microbiota transplantation, dietary interventions, and small-molecule modulators. While preclinical results are promising, clinical trials reveal considerable variability, highlighting the need for personalized approaches and robust biomarkers. Challenges remain in deciphering causal relationships, accounting for inter-individual variability, and ensuring reproducibility in therapeutic outcomes. Future research should integrate multi-omics strategies, longitudinal human cohorts, and mechanistic models to clarify the role of the MGBA in neurodegeneration. Collectively, understanding the MGBA provides a transformative perspective on neurodegenerative disease mechanisms and offers innovative therapeutic avenues that bridge neurology, microbiology, and precision medicine.},
}

Humans
*Neurodegenerative Diseases/therapy/microbiology/metabolism/etiology
*Gastrointestinal Microbiome
*Brain/metabolism
Animals
Dysbiosis
Probiotics/therapeutic use
*Brain-Gut Axis

@article {pmid40951906,
year = {2025},
author = {Telec, W and Al-Saad, S and Karbowski, L and Kłosiewicz, T and Baszko, A},
title = {Postshock Pacing in Cardiac Arrest: A Concise Review.},
journal = {Emergency medicine international},
volume = {2025},
number = {},
pages = {9067144},
pmid = {40951906},
issn = {2090-2840},
abstract = {Following an administered shock in cardiac arrest, the heart commonly experiences a short phase of inability to efficiently perfuse. Despite being a commonly used feature in the ICD population, postshock pacing (PSP) is yet to be adequately explored for its utility in this pulseless phase. Notably, an overwhelming proportion of available data for transcutaneous pacing in spontaneous cardiac arrest stem from the 1980s and 1990s and revolve largely around nonshockable, as opposed to shockable rhythms. The lack of large-scale clinical trials assessing the efficacy of transcutaneous PSP and the considerable advancements in technology and training facilities since the 1990s indicates a need for reevaluation of current understanding of PSP and its applicability in cardiac arrest. Shedding light into the possible implications of transcutaneous PSP in emergency setting cardiac arrest may not only reshape the current protocols of ALS but also carry the potential of improving survival rates. This concise review serves as a summary of the existing knowledge on the subject of PSP and reveals further possible directions for the development of this therapy.},
}

@article {pmid40949612,
year = {2025},
author = {Gao, L and Wang, J and Bi, Y},
title = {Nanotechnology for Neurodegenerative Diseases: Recent Progress in Brain-Targeted Delivery, Stimuli-Responsive Platforms, and Organelle-Specific Therapeutics.},
journal = {International journal of nanomedicine},
volume = {20},
number = {},
pages = {11015-11044},
pmid = {40949612},
issn = {1178-2013},
abstract = {Neurodegenerative diseases-including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis-are characterized by progressive neuronal loss and complex pathological mechanisms such as protein aggregation, mitochondrial dysfunction, and neuroinflammation. Conventional therapies offer limited efficacy due to the blood-brain barrier (BBB) and lack of targeted delivery. Nanotechnology has emerged as a transformative strategy for precise brain-targeted treatment. This review summarizes recent advances in nanoparticle-based drug delivery systems, including polymeric nanoparticles, liposomes, inorganic nanomaterials, and biomimetic carriers, highlighting their design features, BBB-penetration mechanisms, and disease-specific applications. Emphasis is placed on stimuli-responsive nanocarriers that react to pH, reactive oxygen species, or enzyme activity, enabling site-specific drug release. Additionally, organelle-targeting strategies-particularly those directed at mitochondria and lysosomes-are explored for their role in subcellular precision therapy. The integration of diagnostic and therapeutic modalities in theranostic nanoplatforms is also discussed. By consolidating preclinical progress and emerging technologies, this review offers insights into the future of nanomedicine in treating neurodegenerative diseases and lays the groundwork for clinical translation.},
}

@article {pmid40949164,
year = {2025},
author = {Roczkowsky, A and Rachubinski, RA and Hobman, TC and Power, C},
title = {Peroxisomes as emerging clinical targets in neuroinflammatory diseases.},
journal = {Frontiers in molecular neuroscience},
volume = {18},
number = {},
pages = {1642590},
pmid = {40949164},
issn = {1662-5099},
abstract = {Peroxisomes are membrane-bounded organelles that contribute to a range of physiological functions in eukaryotic cells. In the central nervous system (CNS), peroxisomes are implicated in several vital homeostatic functions including, but not limited to, reactive oxygen species signaling and homeostasis; generation of critical myelin sheath components (including ether phospholipids); biosynthesis of neuroprotective docosahexaenoic acid; breakdown of neurotoxic metabolites (such as very-long chain fatty acids); and, intriguingly, glial activation and response to inflammatory stimuli. Indeed, peroxisomes play a critical role in modulating inflammatory responses and are key regulators of the mitochondrial antiviral signaling (MAVS) protein-mediated response to infections. The importance of peroxisomes in CNS physiology is exemplified by the peroxisome biogenesis disorders (PBDs), a spectrum of inherited disorders of peroxisome assembly and/or abundance, that are characterized in part by neurological manifestations ranging from severe cerebral malformations to vision and hearing loss, depending on the individual disorder. Recently, peroxisome dysfunction has been implicated in neurological diseases associated with neuroinflammation including Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson's disease while also contributing to the pathogenesis of neurotropic viruses including SARS-CoV-2, Human Pegivirus, HIV-1 and Zika virus. In the present review, we examine the diverse roles that peroxisomes serve in CNS health before reviewing more recent studies investigating peroxisome dysfunction in inflammatory brain disorders and also highlight potential peroxisomal targets for diagnostic biomarkers and therapeutic interventions.},
}

@article {pmid40943341,
year = {2025},
author = {Yang, EJ},
title = {The Emerging Role of the Brain-Gut Axis in Amyotrophic Lateral Sclerosis: Pathogenesis, Mechanisms, and Therapeutic Perspectives.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
pmid = {40943341},
issn = {1422-0067},
support = {(KIOM) KSN2224011//KIOM/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Although genetic and environmental factors are established contributors, recent research has highlighted the critical role of the gut-brain axis (GBA) in ALS pathogenesis. The GBA is a bidirectional communication network involving neural, immune, and endocrine pathways that connect the gut microbiota with the central nervous system. Dysbiosis in ALS disrupts this axis, leading to increased intestinal permeability, neuroinflammation, and excitotoxicity. Notably, reductions in butyrate-producing bacteria, alterations in microbial metabolites, and enhanced NLRP3 inflammasome activation have been observed in patients with ALS. These changes may precede motor symptoms, suggesting a potential causative role. Interventions targeting the microbiome, such as dietary modulation, have shown promise in delaying disease onset and reducing inflammation. However, the clinical evidence remains limited. Given that gut dysbiosis may precede neurological symptoms, microbiota-targeted therapies offer a novel and potentially modifiable approach to ALS treatment. Understanding the role of GBA in ALS will open new avenues for early diagnosis and intervention. Further clinical trials are required to clarify the causal links and evaluate the efficacy of microbiome-based interventions. Understanding the brain-gut-microbiota axis in ALS could lead to new diagnostic biomarkers and therapeutic strategies.},
}

@article {pmid40905633,
year = {2025},
author = {Verdés, S and Navarro, X and Bosch, A},
title = {Targeting Amyotrophic Lateral Sclerosis with Gene Therapy: From Silencing Genes to Enhancing Neuroprotection.},
journal = {Human gene therapy},
volume = {36},
number = {17-18},
pages = {1173-1198},
doi = {10.1177/10430342251372898},
pmid = {40905633},
issn = {1557-7422},
abstract = {Gene therapy is emerging as a transformative approach for treating amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disease. While gene replacement has shown a groundbreaking success in spinal muscular atrophy, the complexity of ALS-due to frequent gain-of-function mutations and a heterogeneous etiology-presents significant challenges. Importantly, approximately 90% of ALS cases are sporadic, with unknown genetic mutation, further complicating patient stratification and therapeutic targeting. As a result, gene therapy strategies must often address multiple pathological mechanisms simultaneously. So far, current gene therapy strategies aim to either suppress toxic gene expression or promote neuroprotection, predominantly via viral-mediated delivery systems. This review will provide an overview of emerging preclinical and clinical gene therapy approaches for ALS, focusing on two main strategies: gene silencing and neuroprotection. Gene silencing techniques, including antisense oligonucleotides (ASOs), viral-mediated RNA interference, and gene editing, have demonstrated efficacy in reducing mutant gene expression, particularly in SOD1 and C9orf72 models, although clinical translation has so far yielded limited success. The recent Food and Drug Administration's approval of the ASO therapy Qalsody for SOD1-ALS underscores the clinical potential of these approaches. Neuroprotective strategies aim to enhance motor neuron survival through delivery of trophic factors, often targeting both central and peripheral tissues to harness retrograde transport mechanisms. We will discuss the advantages and limitations of various delivery vectors, targeting specificity, timing of intervention, and translational challenges, alongside current clinical trial data. This review aims to synthesize how these approaches may converge to address the multifaceted nature of ALS and guide the development of next-generation therapeutics.},
}

@article {pmid40943213,
year = {2025},
author = {Liu, D and Yu, S and Ji, B and Peng, Q and Gao, J and Zhang, J and Guo, Y and Hu, M},
title = {Molecular Mechanisms of Herbicide Resistance in Rapeseed: Current Status and Future Prospects for Resistant Germplasm Development.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
doi = {10.3390/ijms26178292},
pmid = {40943213},
issn = {1422-0067},
support = {2023ZD0404203//Science and Technology Innovation 2030 Major Program/ ; 31901503//National Natural Science Foundation of China/ ; CARS-12//Agriculture Research System of China/ ; CX (23) 1001//Jiangsu Provincial Agricultural Science and Technology Independent Innovation Fund/ ; BE2021405//Jiangsu Province Key Research and Development Project/ ; },
abstract = {Rapeseed (Brassica napus) is a globally important oilseed crop whose yield and quality are frequently limited by weed competition. In recent years, there have been significant advances in our understanding of herbicide-resistance mechanisms in rapeseed and in the development of herbicide-resistant rapeseed germplasm. Here, we summarize the molecular mechanisms of resistance to three herbicides: glyphosate, glufosinate, and acetolactate synthase (ALS) inhibitors. We discuss progress in the identification of new resistance genes and the development of herbicide-resistant rapeseed germplasm, from the initial identification of natural mutants to artificial mutagenesis screening, introduction of exogenous resistance genes, and gene editing. In addition, we describe how synthetic biology and directed protein evolution will contribute to precision-breeding efforts in the near future. This is the first review to systematically integrate non-target resistance mechanisms and the potential applications of multi-omics and AI technologies for breeding of herbicide-resistant rapeseed, together with strategies for managing the risks associated with gene flow, the evolution of herbicide-resistant weeds, and the occurrence of volunteer plants resulting from deployment of herbicide-resistant rapeseed. By synthesizing current knowledge and future trends, this review provides guidance for safe, effective, and innovative approaches to the sustainable development of herbicide-resistant rapeseed.},
}

@article {pmid40943143,
year = {2025},
author = {Calcagnile, M and Alifano, P and Damiano, F and Pontieri, P and Del Giudice, L},
title = {A Perspective on the Role of Mitochondrial Biomolecular Condensates (mtBCs) in Neurodegenerative Diseases and Evolutionary Links to Bacterial BCs.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
doi = {10.3390/ijms26178216},
pmid = {40943143},
issn = {1422-0067},
support = {project 'NutrAge' (project nr. 7022)//CNR-DISBA/ ; FOE-2019 DBA.AD003.139//CNR/ ; },
abstract = {Biomolecular condensates (BCs), formed through liquid-liquid phase separation (LLPS), are membraneless compartments that dynamically regulate key cellular processes. Beyond their canonical roles in energy metabolism and apoptosis, Mitochondria harbor distinct BCs, including mitochondrial RNA granules (MRGs), nucleoids, and degradasomes, that coordinate RNA processing, genome maintenance, and protein homeostasis. These structures rely heavily on proteins with intrinsically disordered regions (IDRs), which facilitate the transient and multivalent interactions necessary for LLPS. In this review, we explore the composition and function of mitochondrial BCs and their emerging involvement in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. We provide computational evidence identifying IDR-containing proteins within the mitochondrial proteome and demonstrate their enrichment in BC-related functions. Many of these proteins are also implicated in mitochondrial stress responses, apoptosis, and pathways associated with neurodegeneration. Moreover, the evolutionary conservation of phase-separating proteins from bacteria to mitochondria underscores the ancient origin of LLPS-mediated compartmentalization. Comparative analysis reveals functional parallels between mitochondrial and prokaryotic IDPs, supporting the use of bacterial models to study mitochondrial condensates. Overall, this review underscores the critical role of mitochondrial BCs in health and disease and highlights the potential of targeting LLPS mechanisms in the development of therapeutic strategies.},
}

@article {pmid40940798,
year = {2025},
author = {Li, L and Zheng, X and Ma, H and Zhu, M and Li, X and Sun, X and Feng, X},
title = {TREM2 in Neurodegenerative Diseases: Mechanisms and Therapeutic Potential.},
journal = {Cells},
volume = {14},
number = {17},
pages = {},
doi = {10.3390/cells14171387},
pmid = {40940798},
issn = {2073-4409},
abstract = {Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), represent significant global health challenges, affecting millions and straining healthcare systems. These disorders involve progressive neuronal loss and cognitive decline, with incompletely elucidated underlying mechanisms. Chronic neuroinflammation is increasingly recognized as a critical contributor to disease progression. The brain's resident immune cells, microglia, are central to this inflammatory response. When overactivated, microglia and other immune cells, such as peripheral macrophages, can exacerbate inflammation and accelerate disease development. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily that demonstrates high expression on microglia in the central nervous system. TREM2 serves a vital role in regulating phagocytosis, synaptic pruning, and energy metabolism. This review examines the functions of TREM2 in neurodegenerative diseases and its potential as a therapeutic target, aiming to inform future treatment strategies.},
}

@article {pmid40940752,
year = {2025},
author = {Lee, JH and Chang, W and Min, SS and Song, DY and Yoo, HI},
title = {Beyond Support Cells: Astrocytic Autophagy as a Central Regulator of CNS Homeostasis and Neurodegenerative Diseases.},
journal = {Cells},
volume = {14},
number = {17},
pages = {},
doi = {10.3390/cells14171342},
pmid = {40940752},
issn = {2073-4409},
support = {2023//Eulji University/ ; RS-2024-00438628//Korea Health Industry Development Institute/Republic of Korea ; },
abstract = {Autophagy is a fundamental catabolic pathway critical for maintaining cellular homeostasis in the central nervous system (CNS). While neuronal autophagy has been extensively studied, growing evidence highlights the crucial roles of astrocytic autophagy in CNS physiology and pathology. Astrocytes regulate metabolic support, redox balance, and neuroinflammatory responses. These functions are closely linked to autophagic activity. The disruption of astrocytic autophagy contributes to synaptic dysfunction, chronic inflammation, myelin impairment, and blood-brain barrier instability. Dysregulation of astrocytic autophagy has been implicated in the pathogenesis of multiple neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. This review summarizes the molecular mechanisms of autophagy in astrocytes and delineates its role in intercellular communication with neurons, microglia, oligodendrocytes, and endothelial cells. Furthermore, we will discuss current pharmacological approaches targeting astrocytic autophagy, with particular attention to repurposed agents such as rapamycin, lithium, and caloric restriction mimetics. Although promising in preclinical models, therapeutic translation is challenged by the complexity of autophagy's dual roles and cell-type specificity. A deeper understanding of astrocytic autophagy and its crosstalk with other CNS cell types may facilitate the development of targeted interventions for neurodegenerative diseases.},
}

@article {pmid40938039,
year = {2025},
author = {Baroni, A and Moulton, C and Cristina, M and Sansone, L and Belli, M and Tasciotti, E},
title = {Nano- and Microplastics in the Brain: An Emerging Threat to Neural Health.},
journal = {Nanomaterials (Basel, Switzerland)},
volume = {15},
number = {17},
pages = {},
pmid = {40938039},
issn = {2079-4991},
support = {[Ricerca corrente]//Italian Ministry of Health/ ; },
abstract = {Nano- and microplastics (NMPs), with nanoplastics posing higher risks due to their smaller size and greater capacity for cellular and subcellular penetration, are being referred to as ubiquitous environmental neurotoxicants, due to their ability to pass through biological barriers, including the blood-brain barrier (BBB) and nasal olfactory epithelium, and to remain lodged in neural tissue. Upon uptake, such particles disturb neuronal homeostasis by multiple converging pathways, including oxidative stress, mitochondrial dysfunction, pathological protein aggregation, and chronic neuroinflammation, all closely involved with the molecular signatures of neurodegenerative disorders (Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis-ALS). In addition to their neurotoxicity, recent findings suggest that NMPs could disturb synaptic communication and neuroplasticity, thereby compromising the brain's capacity to recover from an injury, a trauma, or neurodegeneration, thus impacting the progression of the disease, our ability to treat it and eventually the efficacy of rehabilitation approaches. Despite these findings, our understanding remains hampered by analytical issues, the scarcity of standard detection methods, and a total lack of longitudinal studies in humans. This review combines multidisciplinary evidence on brain-plastic interactions and calls for accelerated advances in our ability to monitor bioaccumulation in humans, and to integrate neurotoxicology paradigms in the assessment of this underappreciated but growing threat to brain health.},
}

@article {pmid40931498,
year = {2025},
author = {Alemán-Villa, KM and Armienta-Rojas, DA and Camberos-Barraza, J and Rábago-Monzón, ÁR and Camacho-Zamora, A and Osuna-Ramos, JF and Magaña-Gómez, JA and Guadrón-Llanos, AM and Calderón-Zamora, L and Norzagaray-Valenzuela, CD and Valdez-Flores, MA and Picos-Cárdenas, VJ and De la Herrán-Arita, AK},
title = {Neuroinflammation across the spectrum of neurodegenerative diseases: mechanisms and therapeutic frontiers.},
journal = {Neuroimmunomodulation},
volume = {},
number = {},
pages = {1-33},
doi = {10.1159/000548021},
pmid = {40931498},
issn = {1423-0216},
abstract = {Neuroinflammation has emerged as a central and dynamic component of the pathophysiology underlying a wide range of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Far from being a secondary consequence of neuronal damage, inflammatory processes (mediated by microglia, astrocytes, peripheral immune cells, and associated molecular mediators) actively shape disease onset, progression, and symptomatology. This review synthesizes current knowledge on the cellular and molecular mechanisms that govern neuroinflammatory responses, emphasizing both shared and disease-specific pathways. We examine how innate and adaptive immune interactions contribute to neuronal vulnerability and neurodegenerative cascades, and explore the reciprocal communication between systemic and central immune compartments. Particular attention is given to emerging therapeutic strategies aimed at modulating neuroinflammation, including immunomodulatory drugs, glial-targeted interventions, and novel delivery platforms. By integrating findings across disciplines and disease models, we outline key translational challenges and propose future directions to harness neuroinflammation as a therapeutic target in the era of precision medicine. Ultimately, a deeper understanding of neuroimmune dynamics holds promise for redefining both the diagnosis and treatment of neurodegenerative disorders.},
}

@article {pmid40928564,
year = {2025},
author = {Davidow, D and Paul, L and Jones, B and Hohlfeld, A and Rasenyalo, S and Dane, K and Shill, IJ and Hendricks, S},
title = {Player-Level Tackle Training Interventions in Tackle-Collision Sports: A Systematic Scoping Review.},
journal = {Sports medicine - open},
volume = {11},
number = {1},
pages = {103},
pmid = {40928564},
issn = {2199-1170},
abstract = {BACKGROUND: In tackle-collision sports, the tackle has the highest incidence, severity, and burden of injury. Head injuries and concussions during the tackle are a major concern within tackle-collision sports. To reduce concussion and head impact risk, evaluating optimal tackle techniques to inform tackle-related prevention strategies has been recommended. The purpose of this study was to perform a systematic scoping review of player-level tackle training intervention studies in all tackle-collision sports.

METHODS: The Arksey and O'Malley's five-stage scoping review process and Levac et al.'s framework were used, along with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) checklist. The main inclusion criteria were that the study included an intervention aimed at improving a player's tackle abilities, and the intervention had to be delivered/implemented at the player-level in a training setting.

RESULTS: Thirteen studies were included in this review, seven studies in American Football (54%), followed by a combined cohort of rugby union and rugby league players (three studies; 23%), rugby union (two studies; 15%), and one study reported on a rugby league cohort (8%). Studies focused primarily on the tackler, with the intervention incorporating a form of instruction or feedback, delivered through video or an expert coach. Other interventions included an 8-week strength and power training programme, designing practice sessions based on baseline data, and helmetless training in American Football. All interventions demonstrated a favourable change in the outcome measured-which included tackler and ball-carrier kinematics based on motion capture video, tackler proficiency scoring, tackling task analysis, head impact frequencies by xPatch head-impact sensor technology, head impact kinematics using head-impact sensors (helmet or skin patches) and football tackle kinematics with motion capture systems or video.

CONCLUSION: This review shows that a range of studies have been undertaken focusing on player-level training interventions. The quality of studies were rated as 'good', and all studies showed improvements in outcome measures. Coaches and policy makers should ensure tackle technique is profiled alongside other player characteristics, and an evidence-based approach to improving player tackling is adopted, improving both performance and reducing injury risk.

KEY POINTS: Only 13 studies tested or implemented interventions at the player level in tackle-collision sports. The focus of the studies was primarily on the tackler, with the interventions incorporating a form of instruction or feedback, which was delivered through video or an expert coach. Other interventions included an 8-week strength and power training programme, designing practice sessions based on baseline data, and helmetless training in American Football. All interventions demonstrated a favourable change in the outcome measure and provide coaches and policymakers with tackle training insights.

REGISTRATION: The systematic scoping review was prospectively registered with OSF (registration number: https://doi.org/10.17605/OSF.IO/V3KZC).},
}

@article {pmid40924345,
year = {2025},
author = {Kutlubaev, MA and Pervushina, EV and Kiernan, MC},
title = {The nature of fatigue in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {40924345},
issn = {2240-2993},
abstract = {OBJECTIVES: Patients diagnosed with amyotrophic lateral sclerosis (ALS) typically describe symptoms of fatigue. Despite this frequency, the underlying mechanisms of fatigue are poorly understood, and are likely multifactorial. To help clarify mechanisms, the present systematic review was undertaken to determine the risk factors related to fatigue in ALS.

METHODS: A systematic review was conducted using PubMed and Google Scholar databases using key words. From a total of 40,014 articles, 18 articles were included in the final review, following PRISMA guidelines. Meta-regression and subgroup analyses were conducted to study the relationship between fatigue in ALS and different covariates.

RESULTS: Eighteen studies were included in the analysis. A number of factors were investigated, including age, sex, disease severity and duration, site of disease onset, neurophysiological parameters, and respiratory symptoms, depression and anxiety, sleep disorders, and pain. Combined analyses established that participants with ALS who reported fatigue had more severe disease, as confirmed by lower functional rating scores, than those who did not report fatigue. The remaining factors including depression, anxiety and pain, were not found to be related to the onset of fatigue in ALS. Overall, fatigue worsened quality of life in patients diagnosed with ALS.

DISCUSSION: Fatigue in ALS appears to be particularly associated with progressive neurological deficit and disability, linked to both central and peripheral neuromuscular mechanisms.},
}

@article {pmid40922888,
year = {2025},
author = {Kademani, A and Avraam, C and Montenegro, D and Paloh, A and Somannagari, N and Gupta, A and Lafi, AW and Algaba, AE and Islam, R and Fahima, C and Siddiqui, HF},
title = {Exploring the Emerging Role of Stem Cell Therapy in Neurodegenerative Diseases and Spinal Cord Injury: A Narrative Review.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e89629},
pmid = {40922888},
issn = {2168-8184},
abstract = {Neurodegenerative diseases and spinal cord injuries (SCI) pose a significant burden on the healthcare system globally. Diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease precipitate cognitive, motor, and behavioral deficits. Parallelly, spinal cord injuries produce sensory and motor deficits, which are burdensome psychologically, socially, and economically. Current management strategies focus only on symptomatic relief, with no definitive cure. Stem cells have been explored for regenerative therapy. This review focuses on developments, limitations, and future potential of stem cell therapy. Stem cells affect the central nervous system via neuroprotective mechanisms, immunomodulatory effects, and mitigation of oxidative stress. The clinical implications of stem cell therapy in treating neurodegenerative diseases and SCI are debatable due to varied outcomes. Challenges related to sample size, long-term follow-up, and assessment of adverse effects should be mitigated in future research. Researchers are currently exploring optimal stem cell types along with various transplantation strategies. Biomaterials integrated with stem cells are a novel approach for treating neurodegenerative diseases and spinal cord injuries. Certain genetic modifications have shown improved results. Screening patients to ascertain better responses to therapy has proven to be a challenge. Other complications include graft vs. host reaction and degeneration of transplanted neurons due to pathogenesis and tumorigenesis. However, the majority of the potential stem cell therapeutic avenues are in the preclinical stage and are being tested on animal models. Guidelines pertaining to ethical concerns and regulatory frameworks need to be established to unfold the full potential of stem cell therapy in the clinical setting. Recent advances also show an increased need to formulate patient-specific approaches to treatment, ranging from stem cell selection to the technique of transplantation. Ongoing clinical trials can address the current challenges and leverage emerging technologies, leading to definitive treatments for neurodegenerative diseases and spinal cord injuries.},
}

@article {pmid40922457,
year = {2025},
author = {Eroglu, E and Harmanci, N},
title = {Emerging Molecular Targets in Neurodegenerative Disorders: New Avenues for Therapeutic Intervention.},
journal = {Basic & clinical pharmacology & toxicology},
volume = {137},
number = {4},
pages = {e70107},
doi = {10.1111/bcpt.70107},
pmid = {40922457},
issn = {1742-7843},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy/physiopathology/metabolism/genetics ; Animals ; *Molecular Targeted Therapy ; Autophagy/drug effects ; Drug Development ; },
abstract = {Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and frontotemporal dementia represent a significant global health burden with limited therapeutic options. Current treatments are primarily symptomatic and fail to modify disease progression, emphasizing the urgent need for novel, mechanism-based interventions. Recent advances in molecular neuroscience have identified several non-classical pathogenic pathways, including neuroinflammation, mitochondrial dysfunction, impaired autophagy and proteostasis, synaptic degeneration and non-coding RNA dysregulation. In this focused review, we highlight emerging molecular targets such as TREM2, NLRP3, mTOR, TFEB, PINK1 and SIRT3, which offer promising avenues for therapeutic intervention. We also address challenges in target validation and translational drug development, while proposing future research directions that may facilitate the design of more effective treatments. A deeper understanding of these molecular mechanisms is essential for developing disease-modifying strategies to combat neurodegeneration.},
}

Humans
*Neurodegenerative Diseases/drug therapy/physiopathology/metabolism/genetics
Animals
*Molecular Targeted Therapy
Autophagy/drug effects
Drug Development

@article {pmid39708835,
year = {2025},
author = {Davalos, L and Kushlaf, H},
title = {Advances in Disease-Modifying Therapeutics for Chronic Neuromuscular Disorders.},
journal = {Seminars in respiratory and critical care medicine},
volume = {46},
number = {3},
pages = {250-258},
doi = {10.1055/a-2463-3385},
pmid = {39708835},
issn = {1098-9048},
mesh = {Humans ; *Neuromuscular Diseases/drug therapy/physiopathology/therapy ; Chronic Disease ; Myasthenia Gravis/drug therapy ; },
abstract = {Neuromuscular disorders can cause respiratory impairment by affecting the muscle fibers, neuromuscular junction, or innervation of respiratory muscles, leading to significant morbidity and mortality. Over the past few years, new disease-modifying therapies have been developed and made available for treating different neuromuscular disorders. Some of these therapies have remarkable effectiveness, resulting in the prevention and reduction of respiratory complications. For myasthenia gravis (MG), efgartigimod, ravulizumab, rozanolixizumab, and zilucoplan have been Food and Drug Administration (FDA)-approved for the treatment of acetylcholine receptor (AChR) antibody-positive generalized MG in the past 2 years. Rozanolixiumab is also approved for treating MG caused by muscle-specific tyrosine kinase (MuSK) antibodies. The new MG therapeutics target the complement system or block the neonatal fragment crystallizable (Fc) receptors (FcRn), leading to significant clinical improvement. For spinal muscular atrophy (SMA), nusinersen (intrathecal route) and risdiplam (oral route) modify the splicing of the SMN2 gene, increasing the production of normal survival motor neuron (SMN) protein. Onasemnogene abeparvovec is a gene replacement therapy that encodes a functional SMN protein. All SMA medications, particularly onasemnogene abeparvovec, have led to clinically meaningful improvement. For late-onset Pompe disease (LOPD), avalglucosidase alfa has shown a greater improvement in respiratory function, ambulation, and functional outcomes in comparison to alglucosidase alfa, and cipaglucosidase alfa combined with miglustat has shown improvement in respiratory and motor function in a cohort of enzyme replacement therapy-experienced LOPD patients. Amyotrophic lateral sclerosis (ALS) remains a challenge. The two most recent FDA-approved medications, namely sodium phenylbutyrate and tofersen, may slow down the disease by a few months in a selected population but do not stop the progression of the disease.},
}

Humans
*Neuromuscular Diseases/drug therapy/physiopathology/therapy
Chronic Disease
Myasthenia Gravis/drug therapy

@article {pmid40920272,
year = {2025},
author = {Ku, JB and Pak, RJ and Ku, SS and Holland, RD and Kim, HS},
title = {Clinical Efficacy of Stem Cell Therapy in Neurotraumatic and Neurodegenerative Conditions: A Comparative Review.},
journal = {Tissue engineering and regenerative medicine},
volume = {},
number = {},
pages = {},
pmid = {40920272},
issn = {2212-5469},
abstract = {BACKGROUND: Neurotraumatic conditions, such as spinal cord injury, brain injury, and neurodegenerative conditions, such as amyotrophic lateral sclerosis, pose a challenge to the field of rehabilitation for its complexity and nuances in management. For decades, the use of cell therapy in treatment of neurorehabilitation conditions have been explored to complement the current, mainstay treatment options; however, a consensus for standardization of the cell therapy and its efficacy has not been reached in the medical community. This study aims to provide a comparative review on the very topic of cell therapy use in neurorehabilitation conditions in an attempt to bridge the gap in knowledge.

METHODS: Studies were searched from the PubMed database published from 2014 to 2024 employing the terms including but not exclusive to "spinal cord injury," "brain injury," "amyotrophic lateral sclerosis," "regenerative medicine," "cell therapy," and "stem cell." Following the PRISMA 2020 statement, the studies were screened, included, and excluded. Thirty three studies were identified and selected for this review.

RESULTS: Countless researchers investigated the efficacy of various stem cell products for the treatment of numerous neurotraumatic conditions, such as spinal cord injury, traumatic brain injury, and neurodegenerative conditions such as amyotrophic lateral sclerosis. The recent decade of studies suggest that in neurotraumatic conditions, bone-marrow-derived and neural stem cells can be effective, and in neurodegenerative conditions, such as ALS, mesenchymal and neural stem cells can be efficacious.

CONCLUSION: Emerging data from the latest research is encouraging to the patients suffering from neurotraumatic and neurodegenerative conditions, which present themselves as a need for further studies with improved standardization in study design, including cell source specification, differentiation and culture method, and outcome measures to ensure a wide applicability.},
}

@article {pmid40917070,
year = {2025},
author = {Xie, J and Xu, J and Tian, Z and Liang, J and Tang, H},
title = {Extended Insights Into Advancing Multi-Omics and Prognostic Methods for Cancer Prognosis Forecasting.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {30},
number = {8},
pages = {44091},
doi = {10.31083/FBL44091},
pmid = {40917070},
issn = {2768-6698},
mesh = {Humans ; Prognosis ; *Lung Neoplasms/genetics/pathology/therapy/diagnosis ; *Biomarkers, Tumor/genetics ; *Adenocarcinoma of Lung/genetics/pathology ; Genomics/methods ; Gene Expression Regulation, Neoplastic ; *Neoplasms/genetics ; Multiomics ; },
abstract = {Zhang et al.'s recent article utilizes comprehensive single-cell data to identify differences in tumor cell populations, highlighting the CKS1B+ malignant cell subcluster as a potential target for immunotherapy. It develops a prognostic and immunotherapeutic signature (PIS) based on this subcluster, demonstrating good performance in predicting lung adenocarcinoma (LUAD) prognosis. The study also validates the role of PSMB7 in LUAD progression. However, there are areas for improvement. There is a lack of clarity regarding the relationship between the CKS1B+ malignant cell subcluster and the PIS, particularly in terms of why PSMB7 was selected for functional studies. The sequencing data are retrospectively obtained from public databases and lack prospective clinical validation. It is suggested to collect LUAD patient tissues for RT-qPCR and RNA-seq analysis and seek external multi-center validations. Additionally, integrating emerging multi-omics methods is recommended to further validate the findings. Despite these limitations, the study represents progress in understanding LUAD and treatment strategies, and continuous evaluation and refinement of multi-omics and machine learning methods are expected for future research and clinical practice.},
}

Humans
Prognosis
*Lung Neoplasms/genetics/pathology/therapy/diagnosis
*Biomarkers, Tumor/genetics
*Adenocarcinoma of Lung/genetics/pathology
Genomics/methods
Gene Expression Regulation, Neoplastic
*Neoplasms/genetics
Multiomics

@article {pmid40855953,
year = {2025},
author = {Logroscino, G and Giannoni-Luza, S and Urso, D and Hamdi, N},
title = {Heterogeneity of frequencies of motor neuron disease across ethnicities and geographical areas: focus on Arabic countries in the Mediterranean area.},
journal = {Current opinion in neurology},
volume = {38},
number = {5},
pages = {588-595},
doi = {10.1097/WCO.0000000000001415},
pmid = {40855953},
issn = {1473-6551},
mesh = {Humans ; Mediterranean Region/epidemiology ; *Amyotrophic Lateral Sclerosis/epidemiology/ethnology/genetics ; Prevalence ; Incidence ; *Motor Neuron Disease/epidemiology/ethnology ; Registries ; Egypt/epidemiology ; Ethnicity ; },
abstract = {PURPOSE OF REVIEW: Although amyotrophic lateral sclerosis (ALS) epidemiology has been increasingly characterized in many regions, data from Arabic countries remain limited. This review aims to summarize the current knowledge on the burden of ALS in Arabic Mediterranean countries, with a particular focus on Egypt.

RECENT FINDINGS: ALS exhibits significant geographic and ethnic variability in terms of incidence, phenotype, and genetic background. Data from the Global Burden of Disease Study 2021 show that Egypt has one of the lowest age-standardized rates of ALS incidence, prevalence, and mortality in the Mediterranean basin. During the past three decades, Egypt has seen a notable decline in ALS-related Disability-Adjusted Life Years and deaths, in contrast to neighboring countries. A national registry has recently been initiated to enhance epidemiological surveillance in the country.

SUMMARY: ALS in Arabic Mediterranean countries presents a distinct epidemiological profile. These differences likely reflect a combination of genetic, demographic, and healthcare-related factors. Strengthening national registries and promoting regional collaborations will be crucial for gaining a deeper understanding of the determinants of ALS in these underrepresented populations.},
}

Humans
Mediterranean Region/epidemiology
*Amyotrophic Lateral Sclerosis/epidemiology/ethnology/genetics
Prevalence
Incidence
*Motor Neuron Disease/epidemiology/ethnology
Registries
Egypt/epidemiology
Ethnicity

@article {pmid40832750,
year = {2025},
author = {Erdi-Krausz, G and Shaw, PJ},
title = {Antisense oligonucleotide therapy in amyotrophic lateral sclerosis.},
journal = {Current opinion in neurology},
volume = {38},
number = {5},
pages = {574-580},
doi = {10.1097/WCO.0000000000001413},
pmid = {40832750},
issn = {1473-6551},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/therapy/drug therapy ; Humans ; *Oligonucleotides, Antisense/therapeutic use ; Animals ; C9orf72 Protein ; Superoxide Dismutase-1 ; *Genetic Therapy/methods ; Superoxide Dismutase/genetics ; DNA-Binding Proteins/genetics ; },
abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with few treatment options available. The approval of tofersen, an antisense oligonucleotide, for SOD1 -ALS by the FDA and EMA may herald a new era of treatment in these patients.

RECENT FINDINGS: So far, trials against the most common genetic form of ALS, C9orf72 , have been unsuccessful, but new preclinical data may show a promising new direction to take. Clinical trials targeting other, more rare genetic mutations associated with familial ALS are currently underway. Other research assessing the use of ASOs to target aberrant splicing associated with sporadic forms of ALS has also produced promising results in preclinical models, using patient-derived induced cellular models and animal models. These therapies are focussed largely on alleviating and reversing TDP-43 pathology, opening up the possibility of not only arresting disease progression, but reversing neurodegeneration.

SUMMARY: ASO therapies have made some promising steps towards treating familial ALS, particularly SOD1 . Ongoing early clinical/preclinical phase research is underway to utilise this technology in other genetic mutations linked with ALS, as well as in sporadic cases.},
}

*Amyotrophic Lateral Sclerosis/genetics/therapy/drug therapy
Humans
*Oligonucleotides, Antisense/therapeutic use
Animals
C9orf72 Protein
Superoxide Dismutase-1
*Genetic Therapy/methods
Superoxide Dismutase/genetics
DNA-Binding Proteins/genetics

@article {pmid40832743,
year = {2025},
author = {Verde, F},
title = {Neurochemical biomarkers of amyotrophic lateral sclerosis: recent developments.},
journal = {Current opinion in neurology},
volume = {38},
number = {5},
pages = {614-619},
doi = {10.1097/WCO.0000000000001411},
pmid = {40832743},
issn = {1473-6551},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/metabolism/cerebrospinal fluid/blood ; *Biomarkers/blood/cerebrospinal fluid/metabolism ; *Neurofilament Proteins/cerebrospinal fluid/blood/metabolism ; DNA-Binding Proteins/blood ; tau Proteins/blood ; },
abstract = {REVIEW PURPOSE: To provide an overview of the recent developments in the field of neurochemical biomarkers of amyotrophic lateral sclerosis (ALS).

RECENT FINDINGS: Neurofilaments, especially NFL, have been confirmed to be good biomarkers for ALS. NFL may be diagnostically useful but its main role is as prognostic and pharmacodynamic biomarker. Inflammatory biomarkers, especially the chitinases, might also serve as pharmacodynamic biomarkers in treatment trials targeting neuroinflammation. GFAP could reflect cognitive-behavioural impairment. CSF dipeptides are diagnostic biomarkers for ALS caused by the C9ORF72 exanucleotide repeat expansion and may be used to confirm target engagement by experimental drugs. Levels of TDP-43 (virtually the ideal biomarker for ALS) in CSF and plasma have not been demonstrated to be consistently altered in ALS. However, promising advancements have been achieved in seed amplification assays for the protein, in its quantification in plasma extracellular vesicles, and in the measurement of CSF levels of a protein reflecting splicing dysfunction of TDP-43. Finally, blood phosphorylated tau has emerged as an ALS biomarker linked to lower motor neuron (or muscle) pathology.

SUMMARY: NFL is still the best neurochemical biomarker for ALS. However, substantial advances have been recently made, especially regarding detection of TDP-43 and blood phosphorylated tau.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/metabolism/cerebrospinal fluid/blood
*Biomarkers/blood/cerebrospinal fluid/metabolism
*Neurofilament Proteins/cerebrospinal fluid/blood/metabolism
DNA-Binding Proteins/blood
tau Proteins/blood

@article {pmid40832740,
year = {2025},
author = {Lang, C},
title = {Sleep alterations in amyotrophic lateral sclerosis.},
journal = {Current opinion in neurology},
volume = {38},
number = {5},
pages = {606-613},
doi = {10.1097/WCO.0000000000001424},
pmid = {40832740},
issn = {1473-6551},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/physiopathology ; *Sleep Wake Disorders/etiology/physiopathology ; },
abstract = {PURPOSE OF REVIEW: This review summarizes recent evidence on sleep disturbances in amyotrophic lateral sclerosis (ALS), emphasizing their role as intrinsic features of the disease process rather than consequence of motor decline.

RECENT FINDINGS: Emerging data suggest that sleep disturbances such as sleep fragmentation, rapid eye movement sleep (REM) and non rapid eye movement sleep (NREM) alterations and circadian changes often precede classic motor symptoms. Structural and functional hypothalamic changes have been observed in early ALS, suggesting a direct role in sleep-wake dysregulation. In addition, impaired glymphatic clearance during sleep may contribute to neurodegeneration by impairing the removal of protein waste. Polysomnographic studies and cohort data support the presence of prodromal sleep abnormalities in both symptomatic patients and gene mutation carriers. Noninvasive ventilation has shown benefits not only in respiratory management but also in improving sleep quality and overall prognosis.

SUMMARY: Sleep alterations in ALS are increasingly recognized as early indicators and potential modulators of disease progression. The hypothalamus and the glymphatic system emerge as key contributors to these disturbances, highlighting sleep as a therapeutic target. Understanding the role of sleep in ALS pathophysiology may aid in earlier diagnosis and novel intervention strategies aimed at modifying disease course.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/physiopathology
*Sleep Wake Disorders/etiology/physiopathology

@article {pmid40772655,
year = {2025},
author = {He, J and Fan, D},
title = {Amyotrophic lateral sclerosis in Mainland China: clinical translational challenges and opportunities.},
journal = {Current opinion in neurology},
volume = {38},
number = {5},
pages = {596-605},
pmid = {40772655},
issn = {1473-6551},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/epidemiology/therapy/diagnosis ; China/epidemiology ; *Translational Research, Biomedical ; Biomarkers ; },
abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) imposes a growing medical and socioeconomic burden in China. This review synthesizes recent advances in understanding ALS epidemiology, biomarker discovery, therapeutic innovations, and policy frameworks in China. It highlights the urgency of addressing challenges, including fragmented healthcare resources, translational medicine gaps, and regional inequities, while emphasizing China's unique contributions to global ALS research.

RECENT FINDINGS: Chinese ALS cohorts exhibit distinct epidemiological profiles, including a younger mean age of onset and prolonged median survival. Policy initiatives, such as ALS inclusion in rare disease registries and insurance reforms, aim to reduce financial burdens of patients. Multimodal biomarker exploration has advanced integrated diagnostic models combining neurofilament light chain (NfL) and clinical data platforms. Neuroimaging and electrophysiological studies reveal glymphatic dysfunction, white matter degeneration, and neuromuscular junction abnormalities, with novel links to hepatic metabolism. Genomic analyses identify population-specific variants. Therapeutic innovations in China include not only biopharmaceuticals, but also integrative traditional Chinese medicine (TCM) approaches.

SUMMARY: China's ALS landscape is transitioning towards precision medicine through biomarker-guided diagnostics and multidisciplinary care models. Key priorities include establishing a national ALS registry, standardizing biomarker validation, and expanding clinical trials to bridge translational medicine gaps.},
}

Humans
*Amyotrophic Lateral Sclerosis/epidemiology/therapy/diagnosis
China/epidemiology
*Translational Research, Biomedical
Biomarkers

@article {pmid40772638,
year = {2025},
author = {Menge, S and Decker, L and Freischmidt, A},
title = {Genetics of ALS - genes and modifier.},
journal = {Current opinion in neurology},
volume = {38},
number = {5},
pages = {568-573},
pmid = {40772638},
issn = {1473-6551},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Genetic Predisposition to Disease/genetics ; Mitochondria/genetics ; },
abstract = {PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a complex genetic disorder, and the pace of discoveries is very rapid. This review aims at briefly summarizing our current knowledge, and at discussing the progress of the last two years.

RECENT FINDINGS: Common variation in numerous genes and variants in some nuclear-encoded mitochondrial genes were linked to an increased or modified risk of ALS, respectively. Mitochondrial function, i.e. specific mitochondrial haplotypes and loss-of-function variants in mitochondria-related genes, was identified as potent modifier of ALS survival, but not risk. Pioneering analyses of copy number variations in ALS-related genes revealed an increased load in ALS, but causality is unclear. A rare hyperactive variant of ER stress associated transcription factor CREB3 was linked to both substantially decreased ALS risk and slower disease progression. Furthermore, variants in IGFBP7 were linked to rare "ALS reversals", but existence of such phenotypes is controversial.

SUMMARY: Common variation increasing ALS risk contributes to our understanding of sporadic ALS, and novel structural variants have the potential to at least partly explain the missing heritability in ALS. Identification of mitochondrial function and ER stress signaling as potent disease modifiers provide valuable starting points for therapeutic approaches beyond targeting single causative genes.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
*Genetic Predisposition to Disease/genetics
Mitochondria/genetics

@article {pmid40767546,
year = {2025},
author = {Dupuis, L and Robertson, J},
title = {Is amyotrophic lateral sclerosis less severe in mice than in humans?.},
journal = {Current opinion in neurology},
volume = {38},
number = {5},
pages = {581-587},
pmid = {40767546},
issn = {1473-6551},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/physiopathology/pathology ; Animals ; Humans ; *Disease Models, Animal ; Mice ; Gene Knock-In Techniques ; Mice, Transgenic ; },
abstract = {PURPOSE OF REVIEW: We review here novel knock-in models of amyotrophic lateral sclerosis (ALS).

RECENT FINDINGS: Knock-in mouse models of various familial forms of ALS generally display a mild motor phenotype, with limited progression, that do not recapitulate the full-blown clinical picture of ALS.

SUMMARY: ALS is a devastating neurodegenerative disease in humans. Typically manifesting in the fifth or sixth decade of life, ALS leads to progressive motor dysfunction and death, usually within 2-5 years from symptom onset. A subset of ALS cases are dominantly inherited. Over the last 30 years, multiple mouse models of ALS have been generated, and recent advances in mouse genome editing techniques have enabled the generation of mouse strains carrying orthologous mutations in endogenous genes that mirror those causing familial forms of ALS. Intriguingly, many of these knock-in mouse models develop much milder phenotypes than patients with ALS carrying the same mutations. A full-blown ALS clinical phenotype seems to be only elicited upon overexpression of mutant genes beyond the endogenous levels. Here, we review these novel models and argue that these models could represent how ALS manifests in the mouse species. We also evaluate how these models could be used for characterizing mechanisms and preclinical drug evaluation.},
}

*Amyotrophic Lateral Sclerosis/genetics/physiopathology/pathology
Animals
Humans
*Disease Models, Animal
Mice
Gene Knock-In Techniques
Mice, Transgenic

@article {pmid40916690,
year = {2025},
author = {Sharma, S and Gupta, M and Sharma, S},
title = {Exploring Thiophene-Based Pharmacophores as Emerging Therapeutics for Neurodegenerative Disorders.},
journal = {Critical reviews in analytical chemistry},
volume = {},
number = {},
pages = {1-29},
doi = {10.1080/10408347.2025.2554239},
pmid = {40916690},
issn = {1547-6510},
abstract = {Neurodegenerative disorders (NDD) i.e., dementia of the Alzheimer's type, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are a rising worldwide epidemic driven by aging populations and characterized by progressive neuronal impairment. In the face of symptomatic therapies, disease-modifying treatments are beyond reach, for many years, at least, owing to the multifactorial origin, including protein aggregation, oxidative stress, neuroinflammation, and neurotransmitter dysregulation. Here, we point out thiophene, a five-membered heterocyclic sulfur-containing scaffold, as an underinvestigated but highly versatile pharmacophore with great potential in therapeutics of NDD. Here, we provide a systematic review of thiophene derivatives identified between 2006 and 2024, highlighting that these compounds are capable of modulating the aggregation of amyloid-β, inhibiting acetylcholinesterase, alleviating oxidative stress, inhibiting the toxicity of α-synuclein, and restoring neurotransmitter homeostasis. Specific emphasis is placed on their structural malleability, blood-brain barrier penetrability, and multi-targeting, which collectively present advantages over traditional heterocyclic templates. Progress in the areas of structure-activity relationship (SAR)-motivated design, synthetic methods, molecular docking, and preclinical assessment is reviewed, leading to the establishment of lead thiophene scaffolds with micro or nanomolar-range activity. This review also provides future directions, such as the requirement of pharmacokinetic improvement, target verification, and translational research to bridge preclinical discoveries with clinical utility. This article collectively places thiophene derivatives as an innovative chemical platform for the design of next-generation drugs for neurodegenerative diseases.},
}

@article {pmid40914405,
year = {2025},
author = {Wang, J and Li, X and Yang, F and Guo, P and Ren, C and Duan, Z and Bi, M and Kong, Y and Zhang, Y and Lu, J},
title = {Exploration of endoplasmic reticulum stress-related gene markers in amyotrophic lateral sclerosis: a comprehensive analysis of bioinformatics and machine learning.},
journal = {Analytical biochemistry},
volume = {},
number = {},
pages = {115969},
doi = {10.1016/j.ab.2025.115969},
pmid = {40914405},
issn = {1096-0309},
abstract = {This study aimed to investigate potential biomarkers related to Endoplasmic reticulum (ER) stress in Amyotrophic lateral sclerosis (ALS) through a comprehensive bioinformatic approach. The gene expression profiles of ALS patients and healthy controls were downloaded from the Gene Expression Omnibus (GEO) database. ER stress-related genes were collected from the MSigDB databases and document literature. The "limma" R package was employed to detect the differentially expressed ER stress-related genes (DE-ERSGs). Three methods of machine learning were applied to select the hub DE-ERSGs. ROC curves were conducted to evaluate model performance. An external dataset was chosen to evaluate the diagnostic capability of hub genes. The CIBERSORT algorithm was used to evaluate the immune cell infiltration characteristics. Additionally, we constructed a systematic ceRNA regulatory network using Cytoscape software and predicted the possible drug candidates using the Enrichr platform. Molecular docking analysis was used to further validate the binding ability of the candidate drug molecules to the hub genes. Six hub DE-ERSGs (ABCA1, CKAP4, TOR1AIP1, MMP9, EDC4, and ALPP) were identified, and the related models performed well. These hub genes were concentrated in multiple pathways and related to various immune cells. Drugs such as nitroglycerin, diazepam, FENRETINIDE, and edaravone exhibited good binding affinity to the hub genes, indicating that they may be promising drugs for the management of ALS. This study revealed the essential role of ER stress in the pathogenesis of ALS from an integrative perspective, providing guidance for the development of new therapeutic targets and diagnostic strategies.},
}

@article {pmid40909873,
year = {2025},
author = {Wang, X and Dong, B and Gan, Q and Li, J and Wu, P and Guan, Y and Wang, J},
title = {Unraveling the Vicious Cycle: Oxidative Stress and Neurotoxicity in Neurodegenerative Diseases.},
journal = {FASEB bioAdvances},
volume = {7},
number = {8},
pages = {e70041},
pmid = {40909873},
issn = {2573-9832},
abstract = {Oxidative stress is characterized by an imbalance between the production and elimination of free radicals, where the rate of free radical generation surpasses the rate of their removal. This imbalance can lead to tissue and organ damage, contributing to the pathogenesis of various diseases. The nervous system, due to its high oxygen consumption, is particularly susceptible to oxidative stress. Numerous neurotoxins can induce neurotoxicity through oxidative stress, thereby contributing to the onset of neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Furthermore, neurotoxicity can exacerbate oxidative stress by disrupting mitochondrial metabolism and impairing the activity of antioxidant enzymes, thereby intensifying neurotoxic effects. This review examines the mechanisms underlying the interaction between oxidative stress and neurotoxicity and explores strategies to mitigate neurotoxicity by reducing oxidative stress, with the aim of informing future clinical approaches for the treatment of neurodegenerative diseases.},
}

@article {pmid40908745,
year = {2025},
author = {Pask, S and Okwuosa, C and Mohamed, A and Price, R and Young, J and Curtis, T and Henderson, S and Winter-Luke, I and Sunny, A and Chambers, RL and Greenley, S and Johansson, T and Bone, AE and Barclay, S and Higginson, IJ and Sleeman, KE and Murtagh, FE},
title = {Models, components and outcomes of palliative and end-of-life care provided to adults living at home: A systematic umbrella review of reviews.},
journal = {Palliative medicine},
volume = {},
number = {},
pages = {2692163251362567},
doi = {10.1177/02692163251362567},
pmid = {40908745},
issn = {1477-030X},
abstract = {BACKGROUND: There is growing demand for home-based palliative care because of patient preference, and increased number of deaths. Optimal models for community-based palliative and end-of-life care are unknown.

AIM: To identify, synthesise and describe review-level evidence to better understand models of palliative and end-of-life care for adults living at home, and examine components of these models and their association with outcomes.

DESIGN: Systematic umbrella review, using key concepts established a priori from Firth et al. and Brereton et al.''s model descriptions. Quality assessment used AMSTAR-2 or equivalent.

DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Database, Epistemonikos (inception - 2024), supplemented by CareSearch, PROSPERO and citation searches.

RESULTS: From 6683 initial papers, n = 66 reviews were included. Seven models of care were identified; by setting (in-home, outpatient); type of professionals (specialist, integrated, non-specialist); or mode (telehealth, education/training). Components included: holistic person-centred assessment, skilled professionals, access to medicines/care/equipment, patient/family support, advance care planning, integration of services, virtual/remote technology and education. We categorised outcomes into: (i) patient outcomes, (ii) family/informal caregiver outcomes, (iii) professional outcomes and iv) service utilisation/cost outcomes. The 'in-home palliative care' model was most researched with good evidence of positive benefit. Specialist and integrated models of care were next most researched, with evidence of improved patient and service utilisation outcomes. Cost-effectiveness evidence was lacking.

CONCLUSION: This meta-level evidence supports provision of in-home palliative care, with most review level evidence showing positive effect on patient outcomes. There was also evidence to support specialist palliative care and integration of primary palliative care with specialist support.},
}

@article {pmid40907612,
year = {2025},
author = {Kumar, AP and Puthussery, DT},
title = {Regulation of PPAR-γ coactivator-1α and its implication in mitochondrial function and neurodegenerative diseases.},
journal = {Ageing research reviews},
volume = {112},
number = {},
pages = {102887},
doi = {10.1016/j.arr.2025.102887},
pmid = {40907612},
issn = {1872-9649},
abstract = {Peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α, interacts with numerous transcription factors implicated in a wide spectrum of biological responses. It has been identified as a key player in the transcriptional regulation of many mitochondrial components. The activity of PGC1-α is regulated at multiple levels, such as gene expression, transcriptional, post-transcriptional, and post-translational modification. The purpose of this review is to highlight the data supporting PGC1-α-mediated regulation by transcriptional and post-translational modification. We summarize the mechanisms involved in PGC1-α regulation by phosphorylation (AMPK, p38 MAPK, Akt, and GSK3β), acetylation (GCN5, p300, and SRCC), and ubiquitination (E3-ubiquitin ligase). Moreover, the review focuses on the multidomain structure of PGC1-α, its expression in the brain, and the importance of PGC1-α-mediated mitochondrial functions. Mitochondrial dysfunction and impaired energy metabolism are key characteristics of neurodegenerative diseases like Alzheimer's, Huntington's, Parkinson's, amyotrophic lateral sclerosis, and multiple sclerosis. It is associated with reduced PGC1-α expression or activity, resulting in an imbalance in the maintenance of mitochondrial dynamics. In this backdrop, we additionally provide a comprehensive overview of the implication of PGC1-α in the pathogenesis of neurodegenerative disease. Overall, PGC1-α acts as a potential target for therapies to reduce mitochondrial dysfunction associated with neurodegenerative diseases and aid in neuroprotection.},
}

@article {pmid40906916,
year = {2025},
author = {Kakoty, V and Kang, JH and Lee, OH and Oh, DH and Ko, YT},
title = {Grueneberg Ganglion: An Unexplored Site for Intranasal Drug Delivery in Alzheimer's Disease.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.5c00376},
pmid = {40906916},
issn = {1948-7193},
abstract = {Neurological disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis pose significant challenges for treatment. Reasons for the difficulty in finding cures for these conditions include complications in early diagnosis, progressive and irreversible neuronal damage, and the presence of the blood-brain barrier (BBB), which hinders the delivery of drugs to the affected areas of the brain. Intranasal (INL) drug administration has increasingly gained popularity among researchers for targeting neurological conditions, because of its ability to bypass the BBB. However, chronic INL administration leads to nasal mucosa irritation. Additionally, rapid mucociliary clearance, a lack of targeted drug delivery, increased enzymatic degradation, and tight junctions that obstruct drug transport limit the clinical applicability of the INL route. To overcome these challenges, a unique region in the rodent nose, known as the Grueneberg Ganglion (GG), can be considered to be a novel site for INL drug administration. GG is a small structure housed under the snout cartilage of the nasal septum, approximately 1.5 mm from the nasal opening in mice. It is directly connected to the main olfactory bulb through axons. This Perspective aims to expand knowledge on why GG may be a viable option for INL delivery to combat neurological conditions. For better understanding, we have explained the INL administration in GG, using Alzheimer's Disease and INL insulin therapy as a role model for the current review.},
}

@article {pmid40905723,
year = {2025},
author = {Peng, C and Maiuri, T and Truant, R},
title = {Tipping the PARylation scale: Dysregulation of PAR signaling in Huntington and neurodegenerative diseases.},
journal = {Journal of Huntington's disease},
volume = {},
number = {},
pages = {18796397251372667},
doi = {10.1177/18796397251372667},
pmid = {40905723},
issn = {1879-6400},
abstract = {Poly(ADP-ribosyl)ation (PARylation), a crucial post-translational modification, is catalyzed by ADP-ribosyltransferases (ARTs) and has significant implications in various cellular processes, including DNA damage response, cell signaling, and immune processes. Aberrant PAR signaling is implicated in numerous neurodegenerative diseases, including Alzheimer, Parkinson, amyotrophic lateral sclerosis, and cerebellar ataxia, where increased PAR levels and PARP1 activity are commonly observed. However, Huntington disease exhibits a unique characteristic: reduced PAR levels and impaired PARP1 activity even in prodromal phase. This finding challenges the prevailing understanding of PAR's role in neurodegeneration and suggests that dysregulation of PAR signaling, whether through overactivation or suppression, can lead to neuronal dysfunction. Herein, we discuss how this balance may impact neurodegenerative diseases, and possible connections between PAR signaling and emerging modifiers of disease onset identified by HD genome-wide association studies (GWAS).},
}

@article {pmid40905501,
year = {2025},
author = {Huang, Y and Wan, Y and Chen, J and Qin, M and Wang, J and Liang, H},
title = {Knowledge mapping of biomarkers in amyotrophic lateral sclerosis: a comprehensive bibliometric and visual analysis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17582024.2025.2554525},
pmid = {40905501},
issn = {1758-2032},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease, and there is currently an urgent need to identify valuable biomarkers to accelerate diagnosis, optimize treatment and prognosis.

METHODS: To conduct a bibliometric analysis of publications related to "ALS biomarker" over the past 20 years, utilizing the subject search feature of the Web of Science Core Collection along with CiteSpace, VOSviewer, and Bibliometrix.

RESULTS: This review presents a 20-year bibliometric analysis of ALS biomarker research (2004-2024), analyzing 2535 publications showing rising trends. The United States led contributions, with Turner, Martin R as the most productive/cited author. Key research hotspots included cerebrospinal fluid, tdp-43, clinical trial, and neuroinflammation. Topics such as neurofilament light chain, machine learning, and exosomes could potentially represent the cutting edge of future research.

CONCLUSION: In summary, this study uses bibliometric analysis of ALS biomarker research to provide a forward-looking perspective on its future limitations and potential.},
}

@article {pmid40904199,
year = {2025},
author = {Isik, S and Osman, S and Yeman-Kiyak, B and Shamshir, SRM and Sanchez, NME},
title = {Advances in Neurodegenerative Disease Therapy: Stem Cell Clinical Trials and Promise of Engineered Exosomes.},
journal = {CNS neuroscience & therapeutics},
volume = {31},
number = {9},
pages = {e70577},
pmid = {40904199},
issn = {1755-5949},
mesh = {Humans ; *Exosomes/transplantation/metabolism ; *Neurodegenerative Diseases/therapy ; Animals ; *Stem Cell Transplantation/methods/trends ; *Clinical Trials as Topic/methods ; },
abstract = {AIM: This review provides a systematic evaluation of 94 stem cell clinical trials to treat neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease.

METHODS: Data were collected from using relevant search terms, focusing exclusively on stem cell therapy. Of the 8000+ participants in these trials, nearly 70% were enrolled in AD-related studies. Only three Phase 3 studies were conducted, and most trials were in the early phases (Phases 1 and 2). Mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, and embryonic stem cells are used the most to treat neurodegenerative diseases. This review also explores the emerging fields of preclinical and clinical investigations of stem cell-derived exosome-based therapies for neurodegenerative diseases.

RESULTS: Exosomes can cross the blood-brain barrier to deliver therapeutic molecules directly to the brain, offering a less invasive alternative to stem cell transplantation. Mesenchymal stem cell-derived exosomes, in particular, have demonstrated significant potential in preclinical models by reducing neuroinflammation, oxidative stress, and promoting neuronal regeneration. Additionally, recent advances in exosome engineering, including surface modifications, therapeutic agent loading, and transgenic modifications, have improved targeting, stability, blood-brain barrier delivery, and neural cell interactions, enabling targeted and effective treatment. Exosome-based therapies are in the preliminary phases of clinical investigation, with only three clinical trials.

CONCLUSION: Given the increasing interest in exosome therapy, clinical investigations are expected to increase. This growth will be driven by ongoing advancements in exosome technology, a deeper understanding of their therapeutic potential, and escalating demand for innovative treatment strategies for neurodegenerative diseases.},
}

Humans
*Exosomes/transplantation/metabolism
*Neurodegenerative Diseases/therapy
Animals
*Stem Cell Transplantation/methods/trends
*Clinical Trials as Topic/methods

@article {pmid40903341,
year = {2025},
author = {Vedula, P and Ishizuka, K and Hayashida, A and Sueo, K and Sawa, A},
title = {Stress-induced nuclear GAPDH: Scientific update and clinical application.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {},
number = {},
pages = {e00725},
doi = {10.1016/j.neurot.2025.e00725},
pmid = {40903341},
issn = {1878-7479},
abstract = {Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is known as a moonlighting protein beyond its original glycolytic function. Stress-induced nuclear translocation of GAPDH has been reproducibly reported, which results in variety types of cellular responses, including cell death and dysfunction. Blocking this stress-induced cascade has been regarded as a target of drug discovery and development for human disease conditions, particularly for neurological and psychiatric diseases. There are promising small compounds that can block this cascade in cell and animal models. Nevertheless, the clinical trials for Parkinson's disease and amyotrophic lateral sclerosis with one of these compounds Omigapil were unsuccessful. Including these failure cases, this review article discussed the scientific frontline of GAPDH, particularly stress-induced nuclear GAPDH, and its potential for clinical applications.},
}

@article {pmid40901987,
year = {2025},
author = {Sun, Z and Li, C and Leitner, D and Wu, M and Zhang, J and Wisniewski, T and Ge, Y},
title = {Age-related Vascular Alterations in the Choroid Plexus: Novel Insights from Pathophysiology and Imaging Studies.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.0735},
pmid = {40901987},
issn = {2152-5250},
abstract = {The choroid plexus (ChP), a highly vascularized brain structure responsible for cerebrospinal fluid (CSF) production, undergoes significant age-related changes that may contribute to neurodegenerative diseases involving disrupted immune regulation, fluid homeostasis and waste clearance. Compared to other brain regions, vascular research on the ChP remains limited despite its critical role as a central interface between the blood and CSF. This review focuses on age-related vascular and structural alterations in the ChP from both histopathological and neuroimaging perspectives, and explores their impact on CSF dynamics, immune regulation, and the integrity of the blood-CSF barrier (BCSFB). Rather than shrinking, the aging ChP often enlarges due to dystrophic changes, as shown in volumetric MRI studies. Histological studies reveal epithelial degeneration, basement membrane thickening, and stromal fibrosis in the normal aging process. In dementia such as Alzheimer's disease (AD), proteomic studies have identified upregulation of AD- and immune-related proteins, along with downregulation of proteins linked to CSF clearance and metabolic support. Emerging high-resolution contrast-enhanced MRI techniques now allow in vivo visualization of microvascular changes within the ChP, shedding light on its normal and abnormal aging processes. Understanding these alterations is critical, as they may influence the onset and progression of various neurological diseases such as AD, Parkinson's disease (PD), normal pressure hydrocephalus, and amyotrophic lateral sclerosis (ALS). The recent advancements and challenges described in this study underscore the need for deeper investigation into ChP aging to inform future diagnostic and therapeutic strategies of neurodegenerative diseases.},
}

@article {pmid40900744,
year = {2025},
author = {Mani, S and Wasnik, S and Shandilya, C and Srivastava, V and Khan, S and Singh, KK},
title = {Pathogenic synergy: dysfunctional mitochondria and neuroinflammation in neurodegenerative diseases associated with aging.},
journal = {Frontiers in aging},
volume = {6},
number = {},
pages = {1615764},
pmid = {40900744},
issn = {2673-6217},
abstract = {The term "neurodegenerative diseases" (NDDs) refers to a range of aging-associated conditions, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Unique clinical symptoms and underlying pathological mechanisms distinguish each of these illnesses. Although these conditions vary, they share chronic neuroinflammation as a defining characteristic. Protein aggregation and mitochondrial dysfunction are believed to play a role in initiating the neuroinflammatory response and, subsequently, the development and course of these illnesses. Apart from providing energy to the cells, mitochondria are involved in the immunoinflammatory response associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and epilepsy. This involvement is attributed to controlling processes such as inflammasome activation and cell death. Under inflammatory conditions, the underlying regulatory mechanisms for these aging-associated disorders may include calcium homeostasis imbalance, mitochondrial oxidative stress, mitochondrial dynamics, and epigenetics. Various NDDs are linked to neuroinflammation and mitochondrial dysfunction. The linkages between these occurrences are becoming more apparent, but the etiology of these pathologic lesions is yet to be elucidated. This review examines the role of neuroinflammation and mitochondrial dysfunction in the growth and course of NDDs, emphasizing the possibility of identifying novel therapeutic targets to address aging-related neurodegenerative processes and retard the progression of these illnesses.},
}

@article {pmid40897992,
year = {2025},
author = {Quigley, SE and Quigg, KH and Goutman, SA},
title = {Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.},
journal = {CNS drugs},
volume = {},
number = {},
pages = {},
pmid = {40897992},
issn = {1179-1934},
support = {R01NS120926/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; R01TS000344/ACL/ACL HHS/United States ; R01TS000327//Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons. ALS is classically characterized by painless progressive weakness, causing impaired function of limbs, speech, swallowing, and respiratory function. The disease is fatal within 2-4 years, often the result of respiratory failure. The pathologic hallmark for a majority of ALS cases is aberrant cytoplasmic accumulations of the nuclear protein TAR-DNA binding protein (TDP-43). A total of 10-15% of ALS can be attributed to a single gene mutation, known as genetic or "familial" ALS, while the remainder of cases are termed nongenetic or "sporadic" although heritability has been measured in up to 37% in this population. Complex interactions between genetics, environment, and physiologic susceptibility are thought to contribute to disease. Management is primarily supportive in nature, though there are several approved treatments worldwide. This review details the mechanisms and evidence of approved disease-modifying treatments, relevant measures to track disease burden and progression used in clinical trials, and approaches to pharmacologic management of common symptoms in ALS. As there is not currently a cure for ALS, research into the complex pathophysiologic and genetic alterations contributing to disease is of great interest. This review further discusses the current understanding of genetic etiologies and altered physiology leading to disease, such as neuroinflammation, integrated stress response, aberrant proteostasis and mitochondrial dysfunction, among others. The translation of preclinical discoveries into current investigational therapeutics, novel therapeutic categories such as antisense oligonucleotides and stem cell transplantation, as well as future horizons harnessing the power of artificial intelligence in drug development and clinical trials are discussed.},
}

@article {pmid40895800,
year = {2025},
author = {D'Arrigo, C and Labbate, S and Galante, D},
title = {Boosting the Therapeutic Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells via Advanced Preconditioning for Neurodegenerative Disorders.},
journal = {Stem cells international},
volume = {2025},
number = {},
pages = {2616653},
pmid = {40895800},
issn = {1687-966X},
abstract = {Acute and chronic neurodegenerative conditions (NDs) are major causes of disability and mortality worldwide. Acute NDs encompass conditions such as stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). On the other hand, chronic NDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Currently, no definitive cure exists for these diseases, and available therapies focus primarily on slowing the progression of symptoms. Mesenchymal stem cells (MSCs), due to their multilineage differentiation capacity, immunomodulatory abilities, and regenerative properties, have gained attention in regenerative medicine. In recent years, extracellular vesicles (EVs) derived from MSCs have shown great promise as a cell-free therapeutic approach, eliminating the risks associated with direct MSCs use, such as tumorigenicity and poor cell survival after transplantation. EVs have emerged as powerful mediators of intercellular communication and tissue repair, exhibiting immunomodulatory, anti-inflammatory, and proregenerative properties. However, limitations such as low EVs yield and reduced efficacy due to MSCs replicative senescence restrict their therapeutic potential. Preconditioning strategies, including hypoxia, 3D cultures, and biochemical priming, have been explored in other fields to enhance EVs properties, yet their specific application to NDs remains under-reported. This review aims to address this gap by analyzing the preconditioning methods used to boost the therapeutic potential of MSCs-derived EVs for neurodegenerative diseases. These preconditioning strategies may enhance EVs yield, functional cargo, and targeted therapeutic efficacy for treating acute and chronic NDs.},
}

@article {pmid40891578,
year = {2025},
author = {Toyota, S},
title = {Expanding Chemistry of Expanded Helicenes.},
journal = {Chemistry (Weinheim an der Bergstrasse, Germany)},
volume = {},
number = {},
pages = {e02193},
doi = {10.1002/chem.202502193},
pmid = {40891578},
issn = {1521-3765},
support = {23K26637//Japan Society for the Promotion of Science/ ; 20H02721//Japan Society for the Promotion of Science/ ; 23H01944//Japan Society for the Promotion of Science/ ; },
abstract = {Expanded helicenes are interesting compounds created by modifying the original helicene structure through the incorporation of linearly fused benzene rings, enlarging the helical diameter. Motivated by Tilley et al.'s report of a key expanded helicene structure in 2017, several research groups have synthesized such nonplanar aromatic compounds, aiming to explore their impressive structures, properties, and chiroptical performance. This review highlights recent advances in the expanded helicene chemistry through experimental and theoretical studies. The shape and length of helical structures depend on the number and combination of angularly and linearly fused benzene rings. Helical structures are classified using notations, and specific compounds corresponding to each structural form, namely, hexagonal, triangular, rhombic, or others, are introduced herein. As an extension of the molecular design, examples of nonhexagonal and heteroaromatic ring-embedded expanded helicenes are presented. Specifically, this review focuses on how the diameters, lengths, and turn numbers of helical structures depend on dynamic processes involving helical inversion and chiroptical properties (circular dichroism (CD) and circularly polarized luminescence (CPL)). The characteristics and perspectives of this molecular design are also discussed.},
}

@article {pmid40891506,
year = {2025},
author = {Pir, GJ and Buddenkotte, J and Alam, MA and Own, A and Eck, RJ and Kraemer, BC and Mandelkow, E and Steinhoff, M},
title = {TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.70239},
pmid = {40891506},
issn = {1742-4658},
support = {11S-0117 180326//Qatar National Research Fund/ ; //Katharina Hardt Foundation/ ; F99AG088436/NH/NIH HHS/United States ; //Cure Alzheimer's Fund/ ; },
abstract = {TDP-linked proteinopathies, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE), are characterised by pathogenic deposits containing transactive response DNA-binding protein 43 (TDP-43) in the brain and spinal cord of patients. These hallmark pathological features are associated with widespread neuronal dysfunction and progressive neurodegeneration. TDP-43's role as an essential RNA/DNA-binding protein in RNA metabolism and gene expression regulation is clear, but deciphering the intricate pathophysiological mechanisms underpinning TDP-43-mediated neurodegeneration is paramount for developing effective therapies and novel diagnostic tools for early detection before frank neuronal loss occurs. The nematode Caenorhabditis elegans, with highly conserved TDP-43 orthologue TDP-1, serves as a powerful genetic model to investigate the molecular underpinnings of TDP-43 proteinopathies. Here, we provide a brief overview of the structural and functional characteristics of TDP-43 and TDP-1, highlighting their conserved roles in RNA metabolism, stress responses, and neurodegeneration. We then delve into the pathobiology of TDP-43, drawing insights from C. elegans models expressing either monogenic TDP-43 variants or bigenic combinations with ALS-associated risk genes, and discuss how these models have advanced our understanding of the pathomechanisms of TDP-43 proteinopathies. By employing its simplicity and genetic manipulability, we discuss how these models have helped identify chemical and genetic suppressors of TDP-43-induced phenotypes, including small molecules like Pimozide and the probiotic Lacticaseibacillus rhamnosus HA-114, now in clinical trials. This review underscores the translational value of C. elegans in unraveling the biochemical pathways and interactions in TDP-43 proteinopathies that perturb cellular physiology, potentially facilitating mechanism-based therapy development.},
}

@article {pmid40887101,
year = {2025},
author = {Guillot, SJ and Luppi, PH and Dupuis, L and Bolborea, M},
title = {Sleep in neurodegenerative diseases: A focus on melatonin, melanin-concentrating hormone and orexin.},
journal = {Journal of neuroendocrinology},
volume = {},
number = {},
pages = {e70085},
doi = {10.1111/jne.70085},
pmid = {40887101},
issn = {1365-2826},
support = {ANR-16-CE16-0015//Agence Nationale de la Recherche/ ; ANR-16-CE92-0031//Agence Nationale de la Recherche/ ; ANR-19-CE17-0016//Agence Nationale de la Recherche/ ; ANR-20-CE17-0008//Agence Nationale de la Recherche/ ; ANR-24-CE37-4064//Agence Nationale de la Recherche/ ; //TargetALS/ ; //Fondation Thierry Latran/ ; //Association Francaise de Recherche sur la sclérose latérale amyotrophique/ ; //Radala Foundation for ALS Research/ ; //ARSLA/ ; //University of Starsbourg fundation/ ; //Fondation Bettencourt Schueller/ ; DEQ20180339179//Fondation pour la Recherche Médicale/ ; //Axa Research Funds/ ; },
abstract = {Sleep and circadian rest-activity rhythm alterations are recognised as inherent clinical features of various neurodegenerative diseases. Traditionally viewed as secondary manifestations of neurodegeneration, recent studies have revealed that disruptions in circadian rhythm and sleep-wake cycles can precede clinical symptoms and significantly contribute to the underlying pathophysiological progression. In this review, we summarise recent research on the impact of sleep and circadian rhythm alterations in ageing and major neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and frontotemporal dementia, highlighting the roles of melatonin, orexin, and melanin-concentrating hormone (MCH) systems as key regulators at the intersection of sleep and neurodegeneration. We argue that sleep and circadian alterations may serve as early biomarkers and therapeutic targets for these diseases.},
}

@article {pmid40885478,
year = {2025},
author = {Hafiz, B and Aldahlawi, A and Ashqar, A and Hamzah, A and Alotaibi, Y and Bajunaid, K and Baeesa, S},
title = {Outcomes of Surgical Versus Endovascular Treatment of Spinal Dural Arteriovenous Fistula: A Systematic Review and Meta-Analysis.},
journal = {World neurosurgery},
volume = {},
number = {},
pages = {124420},
doi = {10.1016/j.wneu.2025.124420},
pmid = {40885478},
issn = {1878-8769},
abstract = {BACKGROUND: Spinal dural arteriovenous fistulas (SDAVFs) are the most prevalent type of spinal vascular malformation and can lead to progressive neurological impairments if left untreated. Endovascular embolization and microsurgical resection are treatment options, although the optimal treatment method remains a subject of debate.

OBJECTIVE: A comprehensive systematic review and meta-analysis to compare the endovascular and microsurgical treatment outcomes of SDAVFs.

METHODS: An exhaustive literature search was conducted in the PubMed, Embase, Scopus, and Web of Science databases, encompassing publications from 2014 to 2024. A total of 522 patients from seven studies (417 surgical and 105 endovascular) met the inclusion criteria. Information on post-treatment complications, recurrence/failure rates, and functional improvement as assessed by the Aminoff-Logue Scale (ALS) or modified ALS (mALS) was extracted. I[2] statistics were used to evaluate heterogeneity, and random-effects models were used to compute risk ratios (RRs) and odds ratios (ORs).

RESULTS: Compared to endovascular intervention, surgical treatment was linked to significantly lower rates of recurrence or treatment failure (RR: 0.19; 95% CI: 0.09-0.39; p < 0.001), especially in long-term follow-up and thoracic-level studies. With greater ALS/mALS gains and a higher percentage of patients achieving full or partial recovery, functional improvement favored surgery. Although complication types varied, complication rates were similar across modalities (OR: 0.84; 95% CI: 0.48-1.49). Asymmetry in funnel plots indicated possible publication bias in favor of successful surgical outcomes.

CONCLUSION: For SDAVFs, surgical ligation provides better long-term results than endovascular embolization in terms of neurological recovery and recurrence prevention. Even though both procedures are usually safe, surgery is the recommended first-line course of action due to the higher failure and recurrence rates linked to embolization, especially in patients with operable anatomy and progressive symptoms.},
}

@article {pmid40858858,
year = {2025},
author = {Loo, YS and Yusoh, NA and Yap, K and Ng, CS},
title = {Programmable self-replicating JEV nanotherapeutics redefine RNA delivery in ALS.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1282},
pmid = {40858858},
issn = {2399-3642},
support = {PM010CNI000148//International Brain Research Organization (IBRO)/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/therapy/genetics ; Humans ; Animals ; *Encephalitis Virus, Japanese/genetics/physiology ; *Oligonucleotides, Antisense/administration & dosage/genetics ; *Genetic Therapy/methods ; MicroRNAs/genetics ; Virus Replication ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, leading to paralysis and respiratory failure. Current therapies offer limited benefits, highlighting the need for novel therapeutic strategies. Antisense oligonucleotides (ASO) and CRISPR/Cas9 gene editing hold promise, but their effective delivery to the central nervous system (CNS) remains a significant challenge. Here, a potential approach involves utilizing engineered Japanese encephalitis virus (JEV) as a self-replicating nanocarrier for targeted ASO delivery to motor neurons. By leveraging JEV's natural neurotropism and "Trojan horse" mechanism of immune cell-mediated CNS entry, this strategy overcomes the blood-brain and blood-spinal cord barriers (BBB/BSCB). Incorporation of ASO sequences within the JEV genome facilitates co-packaging and sustained therapeutic delivery, while microRNA (miRNA)-mediated attenuation may enhance safety and CNS specificity. This theoretical framework offers a potential paradigm shift in CNS gene therapy for ALS and other neurodegenerative diseases by enabling efficient, targeted, and sustained ASO delivery. However, experimental validation remains critical to assess its safety and therapeutic efficacy.},
}

*Amyotrophic Lateral Sclerosis/therapy/genetics
Humans
Animals
*Encephalitis Virus, Japanese/genetics/physiology
*Oligonucleotides, Antisense/administration & dosage/genetics
*Genetic Therapy/methods
MicroRNAs/genetics
Virus Replication

@article {pmid40884740,
year = {2025},
author = {Kalasa Anil Kumar, AP and Subair, S and Basthikoppa Shivamurthy, P and Ummar, S and Rajeev, AC and Raju, R},
title = {Decoding ATXN2 Phosphocode: Structural Insights and Therapeutic Opportunities in Disease.},
journal = {The protein journal},
volume = {},
number = {},
pages = {},
pmid = {40884740},
issn = {1875-8355},
abstract = {Ataxin-2 (ATXN2), a key RNA-binding protein, regulates RNA metabolism, stress granule formation, and neuronal homeostasis, with dysregulated phosphorylation contributing to Spinocerebellar Ataxia type 2 (SCA2), amyotrophic lateral sclerosis (ALS), and cancer. This review integrates structural biology, phosphoproteomics, and interactome analyses to map six critical phosphosites (S772, T741, S624, S684, S784, S889) within ATXN2's intrinsically disordered regions. Modulated by kinases GSK3β and CDK13 and phosphatases like INPP5F, these sites orchestrate interactions with RNA-binding partners (e.g., ATXN2L, FXR2, STAU2) and co-regulated proteins (e.g., TP53BP1, NUP153), driving pathogenesis through disrupted autophagy, nucleocytoplasmic transport, and stress granule dynamics. We propose targeted therapies, including GSK3β inhibitors for ALS, antisense oligonucleotides for SCA2, and MTOR modulators for cancer, to restore ATXN2 function. By elucidating phosphocode of ATXN2, this work highlights novel avenues for precision medicine in neurodegenerative and oncogenic diseases.},
}

@article {pmid40883656,
year = {2025},
author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P},
title = {Geographic distribution of amyotrophic lateral sclerosis-related genes: a systematic review.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/17582024.2025.2554382},
pmid = {40883656},
issn = {1758-2032},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease. There is no effective treatment, but disease-modifying therapies do exist. Objective. To identify the geographical distribution of ALS-related genes.

METHODS: A systematic review was conducted according to the PRISMA 2020 guidelines in PubMed and Web of Science. Inclusion criteria: patients with ALS, no age or gender restriction, English and Spanish languages, studies published until 31 July 2025.

RESULTS: Thirty-eight results were obtained, 32 were selected, 19 articles were assessed for eligibility, and 8 articles were included from databases. Three articles recommended by clinical experts were added, so 11 results were reviewed. This research showed that published articles on the geographic distribution of ALS-related genes are limited, particularly for underrepresented regions such as Africa.

CONCLUSION: The findings demonstrate the need for intensified international research to improve knowledge of the genetic epidemiology of ALS.},
}

@article {pmid40871062,
year = {2025},
author = {Yang, HM},
title = {Overcoming the Blood-Brain Barrier: Advanced Strategies in Targeted Drug Delivery for Neurodegenerative Diseases.},
journal = {Pharmaceutics},
volume = {17},
number = {8},
pages = {},
pmid = {40871062},
issn = {1999-4923},
support = {03-2025-0200//Seoul National University Hospital/ ; },
abstract = {The increasing global health crisis of neurodegenerative diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's disease is worsening because of a rapidly increasing aging population. Disease-modifying therapies continue to face development challenges due to the blood-brain barrier (BBB), which prevents more than 98% of small molecules and all biologics from entering the central nervous system. The therapeutic landscape for neurodegenerative diseases has recently undergone transformation through advances in targeted drug delivery that include ligand-decorated nanoparticles, bispecific antibody shuttles, focused ultrasound-mediated BBB modulation, intranasal exosomes, and mRNA lipid nanoparticles. This review provides an analysis of the molecular pathways that cause major neurodegenerative diseases, discusses the physiological and physicochemical barriers to drug delivery to the brain, and reviews the most recent drug targeting strategies including receptor-mediated transcytosis, cell-based "Trojan horse" approaches, gene-editing vectors, and spatiotemporally controlled physical methods. The review also critically evaluates the limitations such as immunogenicity, scalability, and clinical translation challenges, proposing potential solutions to enhance therapeutic efficacy. The recent clinical trials are assessed in detail, and current and future trends are discussed, including artificial intelligence (AI)-based carrier engineering, combination therapy, and precision neuro-nanomedicine. The successful translation of these innovations into effective treatments for patients with neurodegenerative diseases will require essential interdisciplinary collaboration between neuroscientists, pharmaceutics experts, clinicians, and regulators.},
}

@article {pmid40870005,
year = {2025},
author = {Jeong, J and Kim, J and Kim, MS},
title = {Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.},
journal = {Genes},
volume = {16},
number = {8},
pages = {},
pmid = {40870005},
issn = {2073-4425},
mesh = {Humans ; *Mitochondria/metabolism/pathology/genetics ; *Stress, Physiological ; Animals ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics ; },
abstract = {BACKGROUND: The mitochondrial integrated stress response (ISR) represents a fundamental cellular adaptation mechanism with dual protective and pathological roles. We critically analyzed current literature on ISR mechanisms, focusing on recent paradigm shifts including the 2020 discovery of the OMA1-DELE1-HRI axis, emerging controversies over context-dependent activation patterns, and the January 2025 clinical trial failures that have reshaped the therapeutic landscape.

METHODS: We reviewed recent literature (2020-2025) examining ISR mechanisms, clinical trials, and therapeutic developments through comprehensive database searches.

RESULTS: The field has evolved from simple linear pathway models to recognition of complex, context-dependent networks. Recent findings reveal that ISR activation mechanisms vary dramatically based on cellular metabolic state, with distinct pathways operating in proliferating versus differentiated cells. The "dark microglia" phenotype in neurodegeneration and DR5-mediated apoptotic switches exemplify pathological ISR manifestations, while adaptive responses include metabolic reprogramming and quality control enhancement.

CONCLUSIONS: The 2025 failures of DNL343 and ABBV-CLS-7262 in ALS trials underscore the need for precision medicine approaches that account for context-dependent ISR functions, temporal dynamics, and disease-specific mechanisms.},
}

Humans
*Mitochondria/metabolism/pathology/genetics
*Stress, Physiological
Animals
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/pathology/genetics

@article {pmid40869392,
year = {2025},
author = {Șerban, M and Toader, C and Covache-Busuioc, RA},
title = {Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
pmid = {40869392},
issn = {1422-0067},
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology/diagnosis ; Humans ; *Biomarkers/metabolism ; Disease Progression ; Animals ; Mitochondria/metabolism ; Precision Medicine ; Neurofilament Proteins/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is still a heterogeneous neurodegenerative disorder that can be identified clinically and biologically, without a strong set of biomarkers that can adequately measure its fast rate of progression and molecular heterogeneity. In this review, we intend to consolidate the most relevant and timely advances in ALS biomarker discovery, in order to begin to bring molecular, imaging, genetic, and digital areas together for potential integration into a precision medicine approach to ALS. Our goal is to begin to display how several biomarkers in development (e.g., neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), TDP-43 aggregates, mitochondrial stress markers, inflammatory markers, etc.) are changing our understanding of ALS and ALS dynamics. We will attempt to provide a framework for thinking about biomarkers in a systematic way where our candidates are not signals alone but part of a tethered pathophysiological cascade. We are particularly interested in the fast progressor phenotype, a devastating and under-characterized subset of ALS due to a rapid axonal degeneration, early respiratory failure, and very short life span. We will try to highlight the salient molecular features of this ALS subtype, including SOD1 A5V toxicity, C9orf72 repeats, FUS variants, mitochondrial collapse, and impaired autophagy mechanisms, and relate these features to measurable blood and CSF (biomarkers) and imaging platforms. We will elaborate on several interesting tools, for example, single-cell transcriptomics, CSF exosomal cargo analysis, MRI techniques, and wearable sensor outputs that are developing into high-resolution windows of disease progression and onset. Instead of providing a static catalog, we plan on providing a conceptual roadmap to integrate biomarker panels that will allow for earlier diagnosis, real-time disease monitoring, and adaptive therapeutic trial design. We hope this synthesis will make a meaningful contribution to the shift from observational neurology to proactive biologically informed clinical care in ALS. Although there are still considerable obstacles to overcome, the intersection of a precise molecular or genetic association approach, digital phenotyping, and systems-level understandings may ultimately redefine how we monitor, care for, and treat this challenging neurodegenerative disease.},
}

*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology/diagnosis
Humans
*Biomarkers/metabolism
Disease Progression
Animals
Mitochondria/metabolism
Precision Medicine
Neurofilament Proteins/metabolism

@article {pmid40869205,
year = {2025},
author = {Lewandowski, D and Konieczny, M and Różycka, A and Chrzanowski, K and Owecki, W and Kalinowski, J and Stepura, M and Jagodziński, P and Dorszewska, J},
title = {Cathepsins in Neurological Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
pmid = {40869205},
issn = {1422-0067},
mesh = {Humans ; *Cathepsins/metabolism ; Animals ; *Nervous System Diseases/metabolism/pathology ; Lysosomes/metabolism ; Biomarkers/metabolism ; },
abstract = {Cathepsins, a family of lysosomal proteases, play critical roles in maintaining cellular homeostasis through protein degradation and modulation of immune responses. In the central nervous system (CNS), their functions extend beyond classical proteolysis, influencing neuroinflammation, synaptic remodeling, and neurodegeneration. Emerging evidence underscores the crucial role of microglial cathepsins in the pathophysiology of several neurological disorders. This review synthesizes current knowledge on the involvement of cathepsins in a spectrum of CNS diseases, including Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, Huntington's disease, and ischemic stroke. We highlight how specific cathepsins contribute to disease progression by modulating key pathological processes such as α-synuclein and amyloid-β clearance, tau degradation, lysosomal dysfunction, neuroinflammation, and demyelination. Notably, several cathepsins demonstrate both neuroprotective and pathogenic roles depending on disease context and expression levels. Additionally, the balance between cathepsins and their endogenous inhibitors, such as cystatins, emerges as a critical factor in CNS pathology. While cathepsins represent promising biomarkers and therapeutic targets, significant gaps remain in our understanding of their mechanistic roles across diseases. Future studies focusing on their regulation, substrate specificity, and interplay with genetic and epigenetic factors may yield novel strategies for early diagnosis and disease-modifying treatments in neurology.},
}

Humans
*Cathepsins/metabolism
Animals
*Nervous System Diseases/metabolism/pathology
Lysosomes/metabolism
Biomarkers/metabolism

@article {pmid40868276,
year = {2025},
author = {Voicu, V and Toader, C and Șerban, M and Covache-Busuioc, RA and Ciurea, AV},
title = {Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteostatic Collapse, and Network Failure Across the CNS.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
pmid = {40868276},
issn = {2227-9059},
abstract = {Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization-spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways-including PI3K-AKT-mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades-undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome-lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3-CR3 axis), and excitatory-inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network "meaning-making"-a collapse of coordinated signal interpretation, triage prioritization, and adaptive response-the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning-a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration.},
}

@article {pmid40868211,
year = {2025},
author = {Flor, J and Silveira, AT and Martins, IA and Otero, LB and Silva, FM and Vizuete, AFK and Wink, MR and Rigatto, K},
title = {Biological Actions of Alamandine: A Scoping Review.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
pmid = {40868211},
issn = {2227-9059},
abstract = {Objective: This scoping review aims to comprehensively map the existing literature on the mechanisms of action of Alamandine (ALA), a peptide within the renin-angiotensin system, and its effects across various physiological systems. Materials and Methods: Utilizing the Joanna Briggs Institute methodology, a thorough search of databases including PubMed, Embase, Scopus, and Web of Science was conducted up to 30 January 2025. The review focused on identifying studies that explore the biological and therapeutic roles of ALA in different contexts, incorporating in vivo, in vitro, and in silico research. Results: A total of 590 records were initially identified, with 25 meeting the eligibility criteria for inclusion in this review. China emerged as the leading contributor to the research in this area, with a significant focus on the cardiovascular system. The studies revealed that ALA exhibits a range of beneficial effects, including anti-inflammatory, vasodilatory, antifibrotic, and antiapoptotic actions. These effects are primarily mediated through the inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway and modulation of the nitric oxide pathway. The review also highlighted AL's potential in mitigating oxidative stress and its implications in treating cardiovascular diseases, fibrosis, and cancer. Conclusions: The findings suggest that ALA holds significant therapeutic potential, offering antihypertensive, anti-inflammatory, antifibrotic, and anticancer benefits without notable adverse effects, warranting further research to explore its full potential and mechanism of action.},
}

@article {pmid40876427,
year = {2025},
author = {Ibrahim, SI and Zaher, DM and Hersi, FA and Hamouda, AO and Al Hindawi, MA and Omar, HA},
title = {Repurposing edaravone in oncology: Bridging antioxidant defense and immune modulation.},
journal = {International immunopharmacology},
volume = {164},
number = {},
pages = {115413},
doi = {10.1016/j.intimp.2025.115413},
pmid = {40876427},
issn = {1878-1705},
abstract = {Edaravone, a synthetic free radical scavenger originally approved for neurological disorders such as stroke and amyotrophic lateral sclerosis (ALS), is gaining attention for its emerging potential role in cancer. Beyond its well-established antioxidant properties, edaravone demonstrates significant anti-inflammatory and immunomodulatory activities, including the inhibition of key pathways such as NF-κB, JAK2/STAT3, and TLR4/IL-6, suggesting potential to modulate immune responses within the tumor microenvironment. This review discusses how edaravone disrupts oncogenic signaling, induces cell cycle arrest, and enhances apoptosis, particularly in cancer stem cells and therapy-resistant models. It also examines edaravone's dual role in combination therapies, where it may improve the cytotoxicity of chemotherapeutic and radiotherapeutic agents while simultaneously protecting normal tissues from treatment-induced toxicities. By linking mechanistic insights with therapeutic outcomes, this review highlights the rationale for repurposing edaravone as a potential adjuvant in cancer therapy. Although clinical data are currently limited, preliminary findings are encouraging and warrant further investigation into edaravone's potential use in cancer treatment regimens.},
}

@article {pmid40866928,
year = {2025},
author = {Tsang, VSK and Malaspina, A and Henson, SM},
title = {The metabolic intersection between immunosenescence and neuroinflammation in amyotrophic lateral sclerosis.},
journal = {Journal of inflammation (London, England)},
volume = {22},
number = {1},
pages = {36},
pmid = {40866928},
issn = {1476-9255},
support = {BBX009610/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons. Although it is traditionally viewed as a neuron-centric disease, neurodegeneration is increasingly linked to immunosenescence and age-related immune dysfunction, but the mechanisms connecting immune ageing to neurodegeneration remain poorly understood. In this review, we explore how metabolic reprogramming, especially the loss of metabolic plasticity in senescent immune cells, drives neuroinflammation in ALS. Senescent immune cells, including microglia and T cells, exhibit mitochondrial dysfunction, redox imbalance, impaired autophagy, and altered nutrient-sensing pathways that impair their homeostatic and reparative capacities. These cells adopt a metabolically demanding pro-inflammatory phenotype, sustaining an inflammatory secretome while promoting glial activation and neuronal damage. Finally, we discuss how targeting immunometabolic pathways may offer new therapeutic opportunities to restore immune balance, mitigate neuroinflammation, and potentially slow ALS progression. Understanding the metabolic basis of immune ageing is essential for developing effective, age-tailored interventions for ALS.},
}

@article {pmid40863128,
year = {2025},
author = {Pawłowska, M and Kruszka, J and Porzych, M and Garbarek, J and Nuszkiewicz, J},
title = {Ketogenic Metabolism in Neurodegenerative Diseases: Mechanisms of Action and Therapeutic Potential.},
journal = {Metabolites},
volume = {15},
number = {8},
pages = {},
pmid = {40863128},
issn = {2218-1989},
abstract = {Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders.},
}

@article {pmid40859959,
year = {2025},
author = {Mao, S and Qiao, R and Wang, Q and Shen, L and Li, D and Huo, X and Wang, J and Liu, K and Chen, W and Zhu, T and Zhang, B and Leng, S and Bai, Y},
title = {Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.},
journal = {MedComm},
volume = {6},
number = {9},
pages = {e70329},
pmid = {40859959},
issn = {2688-2663},
abstract = {Astrocytes, the most prevalent glial cells in the central nervous system (CNS), play crucial roles in maintaining CNS homeostasis and responding to various pathological stimuli. They play key roles in neural development, neurotransmission, neuroinflammation, metabolic support, and tissue repair. Recent advancements in single-cell sequencing have revealed the remarkable heterogeneity of astrocytes, with distinct subpopulations differentially contributing to disease progression in neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, intracerebral hemorrhage, and multiple sclerosis. In addition, they play an important role in various behavioral neuropsychiatric disorders. This review highlights the dual roles of astrocytes in disease progression, driven by their diverse molecular profiles and functions. It outlines the key molecular mechanisms underlying astrocyte heterogeneity and their impact on neuroinflammation, neuronal support, and ionic balance regulation. Additionally, the review discusses potential therapeutic strategies targeting astrocytes to modulate these processes, aiming to improve treatment outcomes in neurological diseases. By elucidating the specific roles of astrocyte subsets in disease, this review seeks to advance the development of precision medicine for astrocyte-related neurological disorders.},
}

@article {pmid40856865,
year = {2025},
author = {Shandilya, C and Mani, S},
title = {Rho kinase isoforms in neurodegeneration: from cellular functions to therapeutic targets.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {846},
pmid = {40856865},
issn = {1573-4978},
mesh = {Humans ; *rho-Associated Kinases/metabolism/antagonists & inhibitors/genetics ; *Neurodegenerative Diseases/metabolism/drug therapy ; Mitochondria/metabolism ; Animals ; Mitophagy ; Neurons/metabolism ; Protein Isoforms/metabolism ; Signal Transduction ; Reactive Oxygen Species/metabolism ; Mitochondrial Dynamics ; Isoenzymes/metabolism ; Oxidative Stress ; },
abstract = {Mitochondria serve as an important cellular organelle for maintaining neurotransmission and synaptic plasticity in neuronal cells by playing a key role in ATP generation, maintaining calcium homeostasis, and regulating the levels of reactive oxygen species (ROS), etc. The regulation of the dynamic nature of mitochondria, including their fission, fusion, and removal of damaged mitochondria by mitophagy, is also very important for neuronal health. Abnormalities in mitochondrial processes, including but not limited to fission, fusion, and mitophagy, are known to be associated with numerous neurodegenerative diseases (NDDs), such as Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). In the recent past, the Rho kinase (ROCK) isoforms, particularly ROCK1 and ROCK2, have gained a lot of attention in NDDs, mainly for their role in regulating the dynamics of the mitochondria, mitophagy, and other cell signalling pathways. By adding phosphate groups to Drp1, ROCK1 is crucial in supporting excessive mitochondrial fission, causing the death of neuronal cells. On the other hand, ROCK2 inhibits Parkin-dependent mitophagy by inhibiting the PTEN protein, the activator of Parkin-dependent mitophagy. This impaired mitochondrial quality control via reduced mitophagic flux leads to oxidative stress and neuronal degeneration, the central pathological feature of NDDs. The inhibition of ROCK isoforms has shown great promise in neuroprotective effects, controlling the dynamics of mitochondria in neuronal cells, lowering inflammation, and improving motor and cognitive functions in preclinical models of different NDDs, indicating ROCK isoforms as an attractive therapeutic target in different NDDs. This review aims to highlight the therapeutic significance of targeting ROCK isoforms in different NDDs.},
}

Humans
*rho-Associated Kinases/metabolism/antagonists & inhibitors/genetics
*Neurodegenerative Diseases/metabolism/drug therapy
Mitochondria/metabolism
Animals
Mitophagy
Neurons/metabolism
Protein Isoforms/metabolism
Signal Transduction
Reactive Oxygen Species/metabolism
Mitochondrial Dynamics
Isoenzymes/metabolism
Oxidative Stress

@article {pmid40849485,
year = {2025},
author = {Helal, MM and AbouShawareb, H and Abbas, OH and Haddad, R and Zain, Y and Osman, ASA and Hassan, AK},
title = {GLP-1 receptor agonists in Parkinson's disease: an updated comprehensive systematic review with meta-analysis.},
journal = {Diabetology & metabolic syndrome},
volume = {17},
number = {1},
pages = {352},
pmid = {40849485},
issn = {1758-5996},
abstract = {Previous studies have demonstrated an increased risk of developing Parkinson's disease (PD) in patients with type 2 diabetes mellitus (T2DM), as well as more severe and rapid motor and non-motor deterioration in diabetic PD patients compared to their non-diabetic counterparts. Additional research has suggested that diabetic subjects treated with glucagon-like peptide-1 (GLP-1) receptor agonists exhibit a reduced incidence of PD compared to those receiving other anti-diabetic medications. GLP-1 receptor agonists are FDA-approved therapies for T2DM, and recent studies have explored their potential as repurposed treatments for neurodegenerative diseases, including PD, AD, and ALS, as well as cerebrovascular disorders. This systematic review aims to assess the available literature on the efficacy and safety profiles of GLP-1 receptor agonists in PD management. A comprehensive search of PubMed, Scopus, CENTRAL, Web of Science, Embase, and ClinicalTrials.gov was conducted to identify relevant studies. The primary outcomes of this review include motor impairment in PD, as assessed by MDS-UPDRS Part III, as well as motor complications (Part IV) and motor experiences of daily living (Part II), and the incidence of gastrointestinal and systemic side effects. Meta-analysis showed that GLP-1 receptor agonists significantly improved motor function, as reflected by MDS-UPDRS Part III scores in the ON state (mean difference = - 2.88; p = 0.01; I[2] = 30%), although they were associated with a higher incidence of adverse events across all safety outcomes. Findings and conclusions of this review will contribute to a clearer understanding of the therapeutic potential of GLP-1 receptor agonists in PD, guiding future clinical research and treatment strategies.},
}

@article {pmid40848858,
year = {2025},
author = {Chen, X and Ma, Y and Liu, H and Wang, Y},
title = {Multifunctional regulation and treatment of ubiquitin specific protease 10.},
journal = {Biochemical pharmacology},
volume = {242},
number = {Pt 1},
pages = {117251},
doi = {10.1016/j.bcp.2025.117251},
pmid = {40848858},
issn = {1873-2968},
abstract = {USP10 is a critical deubiquitinating enzyme within the ubiquitin-specific protease family, playing multifaceted roles in cellular physiology and disease pathogenesis. Structurally composed of a G3BP1-interacting motif, a N-terminal domain (mediating most protein interactions), and a catalytic USP domain (residues 415-795, catalytic triad C424-H736-D751), USP10 regulates diverse cellular pathways by stabilizing key proteins through deubiquitination. It exhibits context-dependent functional duality, particularly in cancer: USP10 promotes tumorigenesis in various cancers (e.g., glioblastoma, esophageal, pancreatic, breast cancers) by stabilizing oncoproteins like CCND1, YAP1, HDAC7, and RUNX1, enhancing proliferation, metastasis, and immune evasion. Conversely, it suppresses tumors (e.g., NSCLC, CRC, thyroid cancer) by stabilizing tumor suppressors like p53, PTEN, and Axin1, inhibiting pathways such as Wnt/β-catenin. Beyond oncology, USP10 contributes to neurodegenerative diseases (neuroprotective in PD/ALS, neurotoxic in AD via Tau stabilization), viral immunity (inhibits SARS-CoV-2 infection), inflammatory responses, male reproduction, and metabolic/cardiovascular disorders. Its regulatory mechanisms include phosphorylation (e.g., by AMPK, AKT, ATM) controlling subcellular localization and activity, and ubiquitination via USP13. USP10's therapeutic significance drives inhibitor development (Spautin-1, D1, Wu-5, P22077, Parthenolide), though cross-reactivity within the USP family due to conserved catalytic domains remains a challenge. Novel strategies like PROTACs and engineered ubiquitin variants (UbVs) offer promise for future selective targeting of USP10 dysregulation in diverse diseases. A comprehensive understanding of its structure and context-specific functions is essential for exploiting its full therapeutic potential.},
}

@article {pmid40840854,
year = {2025},
author = {Fernàndez-Bernal, A and Mota, N and Pamplona, R and Area-Gómez, E and Portero-Otin, M},
title = {Mission cholesterol: Uncovering its hidden role in ALS neurodegeneration.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1871},
number = {8},
pages = {168021},
doi = {10.1016/j.bbadis.2025.168021},
pmid = {40840854},
issn = {1879-260X},
abstract = {Cholesterol is a central determinant of membrane architecture, signaling, and cellular homeostasis in the central nervous system (CNS). While historically viewed as a structural component, emerging evidence highlights its dynamic regulatory role in neuronal function, particularly through its compartmentalized synthesis, trafficking, and turnover. This review examines the complex landscape of cholesterol metabolism in the CNS, emphasizing the cooperative roles of astrocytes and neurons, the partitioning of biosynthetic pathways, and the barriers that distinguish brain cholesterol pools from peripheral sources. We focus on mitochondria-associated endoplasmic reticulum membranes (MAMs) as key regulatory platforms for cholesterol sensing, esterification, and signaling, underscoring their emerging role in neurodegenerative diseases. Disruptions in MAM integrity, lipid raft composition, and transcriptional regulation of cholesterol-handling genes have been linked to pathologies such as amyotrophic lateral sclerosis (ALS), particularly through the actions of TDP-43. By consolidating recent findings from lipidomics, cell biology, and disease models, we propose that cholesterol dyshomeostasis constitutes a shared mechanistic axis across diverse neurodegenerative conditions. Understanding this axis offers novel insights into the metabolic vulnerability of neurons and highlights cholesterol metabolism as a promising target for therapeutic intervention.},
}

@article {pmid40839108,
year = {2025},
author = {Mukherjea, N and Khandelwal, A and Saluja, R and Kalra, N},
title = {The Role of the human microbiome in neurodegenerative diseases: A Perspective.},
journal = {Current genetics},
volume = {71},
number = {1},
pages = {17},
pmid = {40839108},
issn = {1432-0983},
mesh = {Humans ; *Neurodegenerative Diseases/microbiology ; *Microbiota ; Parkinson Disease/microbiology ; *Gastrointestinal Microbiome ; Alzheimer Disease/microbiology ; Inflammasomes ; Inflammation/microbiology ; },
abstract = {Advances in diagnostics, therapeutics, and large-scale clinical studies have significantly expanded our understanding how human health is shaped by the microorganisms that colonize the body since birth. This article explores the rapidly evolving field of human microbiome research, focusing upon how microbial communities influence neurological health and contribute to the development of neurodegenerative diseases (NDs). Multiple factors, including age, lifestyle, and immunological memory, are recognized as major determinants of an individual's microbiome composition, which in turn can influence the onset and the progression of disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These conditions have been linked to mechanisms including the aggregation of pathogenic proteins (e.g., amyloid-β and α-synuclein), inflammation driven by activation of the Toll-like receptor (TLR) signaling pathway, the NLRP3 inflammasome, as well as the modulatory effect of microbial metabolites such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS). The article also highlights ongoing research and emerging strategies aimed at leveraging the human microbiome for better diagnosis, and management of NDs.},
}

Humans
*Neurodegenerative Diseases/microbiology
*Microbiota
Parkinson Disease/microbiology
*Gastrointestinal Microbiome
Alzheimer Disease/microbiology
Inflammasomes
Inflammation/microbiology

@article {pmid40838713,
year = {2025},
author = {Noor, SM and Reddy, DH and Srikanth, Y and Viswanadh, MK and Dumala, N and Chakravarthy, G and Nalluri, BN and Naryanarao, A and Duguluri, S and Yadagiri, G and Prasanna, VS and Sundaram, S and Gujjari, L and Ramakrishna, K},
title = {Morin hydrate: a comprehensive review on therapeutic potential in treating neurological diseases.},
journal = {Nutritional neuroscience},
volume = {},
number = {},
pages = {1-25},
doi = {10.1080/1028415X.2025.2544605},
pmid = {40838713},
issn = {1476-8305},
abstract = {Background: Morin hydrate is a polyphenolic flavonoid present in various vegetables, fruits, nuts, and sea products. It has been reported to offer multiple protective effects against a range of diseases, including cancer, cardiovascular, liver, neurological, metabolic, and renal disorders.Objective: This review highlights the molecular mechanisms and therapeutic potential of Morin in neurological diseases, including Parkinson's disease, Alzheimer's disease, traumatic brain injury, neuropathic pain, stroke, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, depression, anxiety, sleep, encephalopathy, schizophrenia, and psychosis, etc.Methods: The research and review articles were collected from the Pubmed, Scopus, Web of Science, and Google Scholar databases using 'Morin' and the above-mentioned neurological diseases as keywords.Results: The neuroprotective effects of Morin are primarily attributed to its ability to mitigate oxidative stress, inflammation, excitotoxicity, calcium dysregulation, mitochondrial dysfunction, neurotransmitter alterations, protein modifications, and enzymatic inhibition.Conclusion: Despite its promising pharmacological profile, the clinical adaptation of Morin for combating neurological diseases requires further validation through comprehensive preclinical and clinical investigations.},
}

@article {pmid40837865,
year = {2025},
author = {Khan, H and Riaz, H and Ahmed, A and Kiyani, MM and Jawad, SM and Ud Din Shah, SS and Abualait, T and Al-Hussain, F and Li, HT and Bashir, S},
title = {CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models.},
journal = {Regenerative therapy},
volume = {30},
number = {},
pages = {575-583},
pmid = {40837865},
issn = {2352-3204},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by the death of motor neurons in the spinal cord and brain regions, leading to a reduced survival rate in patients. Nearly 20 gene mutations are associated with ALS, with SOD1, FUS, TARDBP, and C9orf72 mutations being more common. Ninety percent of ALS cases are related to sporadic ALS, while the remaining 10 % are associated with familial ALS. CRISPR/Cas9, a genome engineering technology known as clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9, has the potential for gene editing and for studying the underlying mechanisms of ALS in mouse models. This technique enables neuroscientists to reverse mutations found in ALS mouse models, providing new hope for understanding the complexities of ALS. Additionally, this tool can create mutations to probe the functional changes of genetic diseases. Using CRISPR/Cas9 with an in vivo delivery method involving adeno-associated vectors, it is possible to silence mutations in the SOD1-linked ALS mouse model. Some limitations related to CRISPR/Cas9 have been discussed in previous studies and need to be addressed before clinical trials can proceed. In this review-based study, we summarise the latest research on CRISPR/Cas9 genome editing for ALS in mouse models and discuss its limitations and future prospects as well.},
}

@article {pmid40835551,
year = {2025},
author = {Rajsic, S and Treml, B and Breitkopf, R and Lederer, W},
title = {Ethical Considerations for Patients Requiring Extracorporeal Cardiopulmonary Resuscitation.},
journal = {Journal of cardiothoracic and vascular anesthesia},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.jvca.2025.07.032},
pmid = {40835551},
issn = {1532-8422},
abstract = {Immediate recognition of cardiac arrest and the initiation of cardiopulmonary resuscitation (CPR) can significantly improve survival chances. The use of extracorporeal membrane oxygenation during CPR (eCPR) could further enhance survival rates. Current evidence supports the implementation of eCPR as a part of the Advanced Life Support protocol, which may positively affect survival and long-term neurological outcomes and provide additional time for diagnosing and treating the underlying cause of cardiac arrest. Based on the patient's potential for recovery and neurological outcome, multidisciplinary teams can pursue weaning of the patient from mechanical support or withdrawal of care in the case of an unfavorable outcome. These decisions should align with the patient's values, prognosis, and ethical guidelines. A healthcare system that actively promotes eCPR as a standardized part of every Advanced Life Support protocol may face challenges, such as an increased number of patients requiring constant care in long-term care facilities. This could potentially lead to a reduced quality of life and create burdens on patients, families, the healthcare system, and society. Furthermore, in cases of potential organ donation, the principles of beneficence and autonomy may place healthcare providers in significant ethical dilemmas. Given the potential for eCPR to become a standard of care for eligible patients, this work focuses on the ethical and social implications, as well as the impact on the healthcare system.},
}

@article {pmid40831763,
year = {2025},
author = {B S, P and Talwar, P},
title = {Influence of palmitoylation in axonal transport mechanisms in neurodegenerative diseases.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1613379},
pmid = {40831763},
issn = {1662-5102},
abstract = {Progressive functional loss and death of neurons are characteristics of neurodegenerative diseases such as Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). These diseases are often linked with disruptions in axonal transport and synaptic functions. Accumulation of misfolded proteins is observed as a commonly shared pathology for these diseases, where aberrant accumulation of amyloid beta (Aβ), tau, α-synuclein (α-syn) and TAR DNA-binding protein 43 (TDP-43), are found in AD, PD and ALS, respectively. These accumulations are observed to be involved in disrupting axonal transport and compromising neuronal survival. Axonal transport is an essential process where proper functioning of the transport mechanism is important for maintaining neuronal hemostasis by transporting of proteins, organelles and neurotransmitter complexes. This review explores the role of palmitoylation in regulating neuronal axonal transport and their impact on other neuronal functions along with neurodegeneration mechanisms. Palmitoylation is a reversible lipid modification, which is widely studied second to phosphorylation. Enzymes like palmitoyl acyltransferases and acyl-protein thioesterases are responsible for attachment and detachment of palmitic acid causing palmitoylation and depalmitoylation of neuronal proteins. In axonal transport, palmitoylation influences the localization and functioning of the proteins, which connectively plays a role in synaptic stability by interacting with synaptic scaffolding proteins and neurotransmission receptors.},
}

@article {pmid40829685,
year = {2025},
author = {Wang, Y and Zhou, Y and Tian, H and Li, Q and Chen, Y and Wang, L and Yin, Z and Zhou, J and Liang, F},
title = {NF-κB signalling pathway in neurodegenerative diseases: Acupuncture as a potential therapeutic approach.},
journal = {Brain research},
volume = {1865},
number = {},
pages = {149893},
doi = {10.1016/j.brainres.2025.149893},
pmid = {40829685},
issn = {1872-6240},
abstract = {The NF-κB signaling pathway plays a crucial role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, particularly through its role in the regulation neuroinflammation, oxidative stress, protein misfolding, and apoptosis. Emerging evidence suggests that acupuncture modulates the NF-κB pathway, thus offering therapeutic potential by mitigating neuroinflammation, reducing oxidative stress, and protecting mitochondrial function. Specifically, acupuncture inhibits NF-κB activation, downregulates pro-inflammatory mediators like TNF-α and IL-6, and mitigates neurotoxicity and apoptosis. These effects are substantiated in animal models of Alzheimer's and Parkinson's diseases, with preliminary evidence in amyotrophic lateral sclerosis models. However, current studies largely rely on preclinical models with limited acupoint selection, short observation periods, and a lack of standardized protocols, posing challenges for translation to clinical settings. Future research should prioritize well-designed clinical trials, expand acupoint combinations, and explore synergistic effects with conventional therapies, aiming to maximize acupuncture's therapeutic efficacy in neurodegenerative diseases.},
}

@article {pmid40828270,
year = {2025},
author = {Harerimana, A and Pillay, JD and Mchunu, G},
title = {The pitfalls of "toughing it out": mapping stoic attitudes in cancer patients. A scoping review.},
journal = {Medicine, health care, and philosophy},
volume = {},
number = {},
pages = {},
pmid = {40828270},
issn = {1572-8633},
abstract = {Stoicism (with an upper-case 'S') as a life philosophy promotes resilience, self-control and rational acceptance of adversity. In contrast, lower-case stoicism, including pseudo-stoicism or stoic attitudes-characterised by emotional suppression and the silent endurance of pain or hardship-has been linked to adverse health outcomes among cancer patients. Thus, further research is needed to understand the drawbacks of stoic attitudes in cancer patients. This scoping review aims to map stoic attitudes in cancer patients, particularly in relation to potential health consequences. The review adhered to Levac et al.'s framework for scoping reviews. A systematic search was conducted from five electronic databases: CINAHL, Emcare, Medline Ovid, Scopus, and Web of Science. Manual searches were conducted using Google and Google Scholar. A total of 955 records were identified, 526 were screened (title and abstracts), and 450 were excluded. After reviewing 76 full-text articles, 12 studies satisfied the inclusion criteria for data extraction and thematic analysis, consisting of five qualitative and seven quantitative studies. A time frame of 10 years was considered, ranging from 2014 to 2024. This scoping review revealed that pseudo-stoic attitudes in cancer patients often lead to emotional suppression, reduced social support, delayed help-seeking and poor management of symptoms such as pain. These attitudes were linked to poorer psychological outcomes and underreporting of symptoms, especially among older males and rural cancer patients. Studies found that stoic traits were sometimes associated with persistence and treatment adherence among cancer patients. Pseudo-stoicism hinders emotional expression and delays help-seeking, leading to adverse health outcomes; however, stoic attitudes are also associated with adaptive qualities, such as psychological endurance and a commitment to care. Therefore, it is vital to promote balanced coping strategies that honour resilience while encouraging open emotional engagement among cancer patients.},
}

@article {pmid40822241,
year = {2025},
author = {Tan, X and Gao, N},
title = {The emerging role of cellular senescence in amyotrophic lateral sclerosis.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1599492},
pmid = {40822241},
issn = {1662-4548},
abstract = {Cellular senescence is a state of permanent cell cycle arrest and is considered a key contributor to aging and age-related diseases, including amyotrophic lateral sclerosis (ALS). The physiological processes of aging lead to a variety of molecular and cellular phenotypes, and evidence of overlap between ALS and aging-related biomarkers suggests that cell type-specific senescence may be a critical factor in ALS. Senescent microglial cells, astrocytes, and neurons have been detected in ALS patients and animal models. However, while accumulating evidence suggests a potential link between cellular senescence and ALS, this connection remains not yet conclusively established. Importantly, how senescent cells may contribute to the neuropathophysiology of ALS remains largely unknown. Additionally, the growing popularity of anti-aging therapies has highlighted the potential of senescent cell clearance as a promising strategy for treating age-related diseases, including ALS. This review provides an overview of cellular senescence, discusses recent advances in understanding how senescence in different cell types influences ALS pathogenesis, and explores the potential role of anti-senescence therapies in ALS treatment.},
}

@article {pmid40821767,
year = {2025},
author = {Zhao, S and Fu, D and Lin, Y and Sun, X and Wang, X and Wu, X and Zhang, X},
title = {The role of the microbiome on immune homeostasis of the host nervous system.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1609960},
pmid = {40821767},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Homeostasis/immunology ; Animals ; *Central Nervous System/immunology ; Nervous System Diseases/immunology/microbiology ; },
abstract = {The gut microbiota is often termed the "second genome" of the human body. It has been shown to be one of the most significant environmental factors (non-genetic) influencing the onset, progression, and prognosis of various neurological and psychiatric disorders through its interactions with the host immune, nervous, and endocrine systems. Changes in the function and composition of the gut microbiota are strongly associated with amyotrophic lateral sclerosis, autism spectrum disorder, depression, Parkinson's disease, and Alzheimer's disease. This review summarizes the research regarding the associations and regulatory mechanisms between the gut microbiota and the central nervous system in order to explore the role of the gut microbiota in maintaining neural homeostasis.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Homeostasis/immunology
Animals
*Central Nervous System/immunology
Nervous System Diseases/immunology/microbiology

@article {pmid40821656,
year = {2025},
author = {Sanghai, N and Tranmer, GK},
title = {Use of Proteomics to Explore Biomarkers of Amyotrophic Lateral Sclerosis (ALS): Proof of Principle from Humanized SOD1 Mouse to Human ALS.},
journal = {ACS pharmacology & translational science},
volume = {8},
number = {8},
pages = {2415-2430},
pmid = {40821656},
issn = {2575-9108},
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare motor neurodegenerative disease affecting multiple cellular proteins during the progression of the disease. ALS was first discovered by Charcot in 1869, and since then, scientists have been unable to identify a singular cause of the disease. Further, there are no effective treatments available to cure ALS. The benchmark discovery of humanized preclinical SOD1 mouse models, which recapitulates the clinical and pathological phenotypes of human ALS, gives hope to medicinal chemists and neuroscientists around the globe that a suitable drug-like molecule can be discovered and translated into human beings as a means to slow down the progression of the disease. However, little success has been achieved until now in terms of finding an effective treatment for heterogenic and incurable ALS. One area marked for improvement is the use of semiquantitative, antibody-based targeted Western blotting (WB) experiments, which lack the power to analyze multiple cellular events within the entire dysregulated proteomic system. With the inconsistency of WB experiments, unexpected cellular pathways go undiscovered, and hence, loss of translation with no target engagement is seen from preclinical to human clinical ALS. Recent advancements in discovery-based quantitative proteomics have many advantages over WB. These innovative techniques could help solve the inherent problem in WB and their inability to discover multiple altered proteins with the added capability of longitudinal analysis in preclinical SOD1 models, further validating the findings in human ALS. Herein, we applied a holistic approach to summarize various reports on the use of proteomics in ALS from the published literature, and importantly, we found that using a discovery-based proteomics approach in SOD1 preclinical ALS models has revealed a more diverse and global picture of pathological proteins that affect multiple pathways during different stages of disease progression. Furthermore, we found that the proteomic profiling of the humanized SOD1 mouse model provided a proof of principle for translating the diverse pathological biomarker proteins identified in clinical human ALS cases. Moreover, we believe that advancements in the proteomics approach toward ALS biomarkers could bridge the gap between preclinical and clinical studies, enabling scientists worldwide to discover novel biomarkers and treatments that modify the progression of ALS.},
}

@article {pmid40819701,
year = {2025},
author = {Haslam, AX and Blandón, MDMT and Castro, ASR},
title = {Ocular manifestations in Dengue Fever: A Systematic Review and Meta-Analysis.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2025.08.021},
pmid = {40819701},
issn = {1879-1891},
abstract = {TOPIC: Ocular manifestations in dengue fever remain underrecognized despite reports of vision-threatening complications. This systematic review and meta-analysis aimed to determine the pooled prevalence of ocular manifestations in dengue patients, characterizing their spectrum, frequency, and clinical significance.

CLINICAL RELEVANCE: Dengue fever affects millions globally, predominantly in tropical regions. While systemic complications are well documented, ophthalmic involvement remains poorly defined, with variable prevalence estimates and unclear risk factors. Early recognition is crucial for timely intervention, particularly in endemic areas where clinical suspicion is low.

METHODS: A comprehensive search was conducted in PubMed, CINAHL, and LILACS. Eligible studies included observational studies reporting the prevalence of ocular manifestations in dengue patients. Risk of bias was assessed using Hoy et al.'s tool for prevalence studies. Pooled prevalence estimates were calculated using a random-effects model, and heterogeneity was assessed using I[2] statistics.

RESULTS: A total of 32 studies, including 11,426 patients, were included. The pooled prevalence of ocular manifestations, calculated from 16 studies, was 0.32 (95% CI: 0.22-0.45, I[2] = 91.8%). Retro-ocular pain had a pooled prevalence of 0.20 (95% CI: 0.10-0.37, I[2] = 99.6%), while blurred vision was reported in 0.11 (95% CI: 0.05-0.23, I[2] = 92.8%). Among structural manifestations, subconjunctival hemorrhage had a prevalence of 0.18 (95% CI: 0.10-0.30, I[2] = 94.1%), retinal hemorrhage 0.08 (95% CI: 0.05-0.12, I[2] = 77.8%), maculopathy 0.04 (95% CI: 0.02-0.08, I[2] = 91.6%), and uveitis 0.05 (95% CI: 0.01-0.24, I[2] = 97.4%). Significant heterogeneity was observed across studies, likely due to differences in diagnostic criteria, study populations, and disease severity.

CONCLUSION: This study highlights a substantial prevalence of ocular manifestations in dengue patients, emphasizing the need for increased clinical awareness, particularly in endemic regions. Given the heterogeneity in reported prevalence, future research should focus on prospective, standardized ophthalmologic assessments to improve early diagnosis and management.},
}

@article {pmid40817956,
year = {2025},
author = {Mannan, A and Sharma, A and Singh, TG},
title = {Boosting Brain Clean-Up: Can Targeting UPS Genes Offer Neuroprotection?.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {40817956},
issn = {1559-1182},
abstract = {The ubiquitin-proteasome system (UPS) plays a critical role in protein homeostasis within eukaryotic cells. This review article examines the UPS's role in neuronal morphology and neurodegeneration through systematic analysis of current research. In neurodegenerative disorders (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), UPS dysfunction contributes significantly to pathogenesis through accumulation of ubiquitinated misfolded proteins, disruption of cellular proteostasis, impaired substrate ubiquitination, and proteasomal deterioration. The UPS maintains normal central nervous system (CNS) function by regulating protein degradation. When this system fails, cellular proteostasis becomes compromised, accelerating neurodegeneration. Recent research has identified potential interventions for UPS activation through genetic modification and synthetic compounds. This review assesses how specific UPS components could serve as pharmacological targets for treating NDDs. By modulating UPS-mediated genes and pathways, novel therapeutic strategies may emerge for conditions including AD, PD, HD), and ALS. Current evidence suggests the UPS represents a promising therapeutic target for addressing the fundamental protein homeostasis disruptions underlying these devastating neurological conditions. Targeting this system could potentially slow disease progression by restoring proper protein degradation mechanisms and preventing toxic protein accumulation characteristic of NDDs.},
}

@article {pmid40817431,
year = {2025},
author = {SyBing, AB and Chen, H and Wang, DD},
title = {Re-Evaluation of Fixed Dosing Versus Body Size-Based Dosing Approaches for Large Molecule Therapeutics in Adults.},
journal = {Clinical pharmacology and therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1002/cpt.70015},
pmid = {40817431},
issn = {1532-6535},
abstract = {Wang et al.[1] (2009) and Zhang et al.[2] (2011) recommended a fixed dosing approach for large molecule therapeutics for first-in-human (FIH) trials, based on the finding that the majority of α values (body size effect on clearance) were < 0.5 across 12 monoclonal antibodies (mAbs) and 18 therapeutic proteins (TPs) and peptides, and fixed dosing provides advantages such as convenience, reduced medical errors, and cost-effectiveness. They also recommended that the approved dosing approach should be determined by α and the therapeutic window. This review aims to re-evaluate these recommendations using a larger dataset (N = 143) of diverse molecules. Results showed 62% (78/126) of non-ADC drugs were approved with fixed dosing, and 58% (28/48) of non-ADC drugs approved with body size-based dosing had an α < 0.7 where fixed dosing would be appropriate. Therefore, only the remaining 16% (20/126) of non-ADC drugs required body size-based dosing. In addition, the FIH dosing approach had significant implications on the approved dosing approach with 68% (90/133) of drugs using the same dosing approach in FIH and approval. Lastly, of non-ADC drugs evaluated, 56% (71/126) demonstrated a relationship between α and the approved dosing approach. When α did not explain the approved dosing approach, lack of clinically meaningful differences in exposure (49%, 27/55) was the most common justification. These findings confirm Wang et al.'s and Zhang et al.'s previous conclusions, continuing to support their recommendations. Based on these insights, a decision tree is proposed for selecting the appropriate dosing approach at each stage of drug development.},
}

@article {pmid40813983,
year = {2025},
author = {Wang, YT and Li, Q and Liu, JC and Chen, C and Ding, HX and Zha, X and Zhang, K},
title = {Cystatin F-a key player in central nervous system disease.},
journal = {Journal of neuroinflammation},
volume = {22},
number = {1},
pages = {203},
pmid = {40813983},
issn = {1742-2094},
support = {81901005//National Natural Science Foundation of China/ ; 81571046//National Natural Science Foundation of China/ ; 2022-MS-203//Natural Science Foundation of Liaoning Province/ ; JYTMS20230122//Basic Scientific Research Project of the Education Department of Liaoning Province/ ; LJKZ0755//Educational Department of Liaoning province/ ; 2023JH2/20200116//Department of Science & Technology of Liaoning province/ ; },
mesh = {Humans ; *Central Nervous System Diseases/metabolism ; Animals ; *Cystatins/metabolism ; Biomarkers, Tumor ; },
abstract = {Cystatin F is an endogenous cysteine protease inhibitor that belongs to the type II cystatin family. It has several unique characteristic structures that determine some of its specific functions. Cystatin F is expressed predominantly in peripheral immune cells and in the microglia of the central nervous system (CNS). Under physiological conditions, the expression of cystatin F in the CNS is minimal. However, emerging evidence suggests that it is significantly upregulated in several CNS diseases. Intriguingly, the role of cystatin F differs across disease contexts-serving a neuroprotective function while promoting pathological progression. Moreover, its function may shift across different pathological stages within the same disorder, reflecting a multifaceted pathophysiology. Cystatin F primarily acts by modulating neuroinflammation, clearing debris, and orchestrating immune responses via its selective expression in disease-associated microglia. As a vital player in CNS diseases, various intervention strategies targeting cystatin F have been proposed, including receptor-interacting protein kinase 1 pathway inhibition, miRNA targeting, mRNA stabilization, necroptosis inhibition, transcriptional regulation and upstream pathway modulation. Several approaches have yielded encouraging results in preclinical models, underscoring the therapeutic potential of modulating cystatin F activity. This review provides a comprehensive overview of the structural features, biological functions, and diverse roles of cystatin F in CNS diseases, including Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stroke, Aicardi-Goutières syndrome, prion disease, and glioblastoma. Recent advances in therapeutic interventions focusing on cystatin F have been critically assessed, and key challenges related to clinical translation are outlined, offering new perspectives on therapeutic directions.},
}

Humans
*Central Nervous System Diseases/metabolism
Animals
*Cystatins/metabolism
Biomarkers, Tumor

@article {pmid40810164,
year = {2025},
author = {Alo, B and Lamers, C},
title = {Crossing Barriers: Advancements in Macromolecular Therapeutics for Neurodegenerative Diseases and Strategies to Overcome the Blood-Brain Barrier.},
journal = {ACS pharmacology & translational science},
volume = {8},
number = {8},
pages = {2353-2383},
pmid = {40810164},
issn = {2575-9108},
abstract = {Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, present considerable challenges for our societies and health systems due to their progressive nature, the demographic shift toward older populations, and limited treatment options. Recent advances in macromolecular therapeutics, including antibodies, peptides, and proteins, offer novel therapeutic modalities for a broad range of diseases. Their high potency and specificity hold promise for disease-modifying therapies to combat neurodegenerative diseases. However, the blood-brain barrier poses a significant challenge for the effective delivery of these large molecules to the central nervous system. This review discusses the physiological role of the blood-brain barrier and its influence on restricting the exposure of macromolecules in the brain. Furthermore, emerging strategies for enhancing blood-brain barrier permeability to macromolecules are highlighted. This review summarizes modifications designed to utilize receptor-mediated uptake, adsorptive-mediated transcytosis, carrier-mediated transport, and nanoparticle-based delivery systems to overcome the blood-brain barrier. Additionally, we emphasize the importance of testing macromolecular therapeutics for their blood-brain barrier permeability and review the methods for such in vitro and in vivo testing. Finally, we shed light on therapeutics in preclinical and clinical development for neurodegenerative diseases and their challenges.},
}

@article {pmid40807333,
year = {2025},
author = {Godela, A and Rogacz, D and Pawłowska, B and Biczak, R},
title = {Natural Neuroinflammatory Modulators: Therapeutic Potential of Fungi-Derived Compounds in Selected Neurodegenerative Diseases.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {15},
pages = {},
pmid = {40807333},
issn = {1420-3049},
mesh = {Humans ; *Neurodegenerative Diseases/drug therapy ; *Fungi/chemistry ; *Biological Products/therapeutic use/pharmacology/chemistry ; Animals ; },
abstract = {Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis remain incurable. Current therapeutic strategies primarily focus on slowing disease progression, alleviating symptoms, and improving patients' quality of life, including the management of comorbid conditions. Over the past few decades, the incidence of diagnosed neurodegenerative disorders has risen significantly. As the number of affected individuals continues to grow, so does the urgent need for effective treatments that can halt or mitigate the progression of these diseases. Among the most promising therapeutic resources are bioactive compounds derived from fungi. The high quality of proteins, polysaccharides, unsaturated fatty acids, triterpenoids, sterols, and secondary metabolites found in fungi have attracted growing interest from researchers across multiple disciplines. One intensively studied direction involves the use of naturally occurring fungi-derived nutraceuticals in the treatment of various diseases, including neurodegenerative conditions. This article provides an overview of recent findings on fungal compounds-such as phenolic compounds, carbohydrates, peptides and proteins, and lipids-that may have potential applications in the treatment of neurodegenerative diseases and the alleviation of their symptoms.},
}

Humans
*Neurodegenerative Diseases/drug therapy
*Fungi/chemistry
*Biological Products/therapeutic use/pharmacology/chemistry
Animals

@article {pmid40806770,
year = {2025},
author = {Sharbafshaaer, M and Pepe, R and Notariale, R and Canale, F and Tessitore, A and Tedeschi, G and Trojsi, F},
title = {Neuroaxonal Degeneration as a Converging Mechanism in Motor Neuron Diseases (MNDs): Molecular Insights into RNA Dysregulation and Emerging Therapeutic Targets.},
journal = {International journal of molecular sciences},
volume = {26},
number = {15},
pages = {},
pmid = {40806770},
issn = {1422-0067},
support = {PERMEALS PNRR-MAD-2022-12375731//Italian Ministry of Health/ ; },
mesh = {Humans ; *Motor Neuron Disease/genetics/metabolism/pathology/therapy ; Animals ; *RNA/genetics/metabolism ; *Axons/pathology/metabolism ; *Nerve Degeneration/genetics/pathology ; Molecular Targeted Therapy ; },
abstract = {Motor Neuron Diseases (MNDs) such as Amyotrophic Lateral Sclerosis (ALS), Primary Lateral Sclerosis (PLS), Hereditary Spastic Paraplegia (HSP), Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1), Multisystem Proteinopathy (MSP), Spinal and Bulbar Muscular Atrophy (SBMA), and ALS associated to Frontotemporal Dementia (ALS-FTD), have traditionally been studied as distinct entities, each one with unique genetic and clinical characteristics. However, emerging research reveals that these seemingly disparate conditions converge on shared molecular mechanisms that drive progressive neuroaxonal degeneration. This narrative review addresses a critical gap in the field by synthesizing the most recent findings into a comprehensive, cross-disease mechanisms framework. By integrating insights into RNA dysregulation, protein misfolding, mitochondrial dysfunction, DNA damage, kinase signaling, axonal transport failure, and immune activation, we highlight how these converging pathways create a common pathogenic landscape across MNDs. Importantly, this perspective not only reframes MNDs as interconnected neurodegenerative models but also identifies shared therapeutic targets and emerging strategies, including antisense oligonucleotides, autophagy modulators, kinase inhibitors, and immunotherapies that transcend individual disease boundaries. The diagnostic and prognostic potential of Neurofilament Light Chain (NfL) biomarkers is also emphasized. By shifting focus from gene-specific to mechanism-based approaches, this paper offers a much-needed roadmap for advancing both research and clinical management in MNDs, paving the way for cross-disease therapeutic innovations.},
}

Humans
*Motor Neuron Disease/genetics/metabolism/pathology/therapy
Animals
*RNA/genetics/metabolism
*Axons/pathology/metabolism
*Nerve Degeneration/genetics/pathology
Molecular Targeted Therapy

@article {pmid40806624,
year = {2025},
author = {Șerban, M and Toader, C and Covache-Busuioc, RA},
title = {The Redox Revolution in Brain Medicine: Targeting Oxidative Stress with AI, Multi-Omics and Mitochondrial Therapies for the Precision Eradication of Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {15},
pages = {},
pmid = {40806624},
issn = {1422-0067},
mesh = {Humans ; *Oxidative Stress/drug effects ; *Mitochondria/metabolism/drug effects ; *Neurodegenerative Diseases/metabolism/therapy/drug therapy ; *Artificial Intelligence ; Oxidation-Reduction ; Antioxidants/therapeutic use/pharmacology ; Biomarkers/metabolism ; *Precision Medicine/methods ; Animals ; Reactive Oxygen Species/metabolism ; Brain/metabolism ; Multiomics ; },
abstract = {Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce protein misfolding, and promote chronic neuroinflammation, creating a positive feedback loop of neuronal damage and cognitive decline. Despite its centrality in promoting disease progression, attempts to neutralize oxidative stress with monotherapeutic antioxidants have largely failed owing to the multifactorial redox imbalance affecting each patient and their corresponding variation. We are now at the threshold of precision redox medicine, driven by advances in syndromic multi-omics integration, Artificial Intelligence biomarker identification, and the precision of patient-specific therapeutic interventions. This paper will aim to reveal a mechanistically deep assessment of oxidative stress and its contribution to diseases of neurodegeneration, with an emphasis on oxidatively modified proteins (e.g., carbonylated tau, nitrated α-synuclein), lipid peroxidation biomarkers (F2-isoprostanes, 4-HNE), and DNA damage (8-OHdG) as significant biomarkers of disease progression. We will critically examine the majority of clinical trial studies investigating mitochondria-targeted antioxidants (e.g., MitoQ, SS-31), Nrf2 activators (e.g., dimethyl fumarate, sulforaphane), and epigenetic reprogramming schemes aiming to re-establish antioxidant defenses and repair redox damage at the molecular level of biology. Emerging solutions that involve nanoparticles (e.g., antioxidant delivery systems) and CRISPR (e.g., correction of mutations in SOD1 and GPx1) have the potential to transform therapeutic approaches to treatment for these diseases by cutting the time required to realize meaningful impacts and meaningful treatment. This paper will argue that with the connection between molecular biology and progress in clinical hyperbole, dynamic multi-targeted interventions will define the treatment of neurodegenerative diseases in the transition from disease amelioration to disease modification or perhaps reversal. With these innovations at our doorstep, the future offers remarkable possibilities in translating network-based biomarker discovery, AI-powered patient stratification, and adaptive combination therapies into individualized/long-lasting neuroprotection. The question is no longer if we will neutralize oxidative stress; it is how likely we will achieve success in the new frontier of neurodegenerative disease therapies.},
}

Humans
*Oxidative Stress/drug effects
*Mitochondria/metabolism/drug effects
*Neurodegenerative Diseases/metabolism/therapy/drug therapy
*Artificial Intelligence
Oxidation-Reduction
Antioxidants/therapeutic use/pharmacology
Biomarkers/metabolism
*Precision Medicine/methods
Animals
Reactive Oxygen Species/metabolism
Brain/metabolism
Multiomics

@article {pmid40806469,
year = {2025},
author = {Wang, J and Shen, Y and Liao, P and Yang, B and Jiang, R},
title = {Roles of Ion Channels in Oligodendrocyte Precursor Cells: From Physiology to Pathology.},
journal = {International journal of molecular sciences},
volume = {26},
number = {15},
pages = {},
pmid = {40806469},
issn = {1422-0067},
support = {82401445//National Natural Science Foundation of China/ ; 82271249//National Natural Science Foundation of China/ ; 2024M752251//China Postdoctoral Science Foundation/ ; 2024NSFSC1636//Sichuan Science and Technology Program/ ; 2024HXBH013//Post doctor Research Fund of West China Hospital of Sichuan University/ ; ZYYC23002//1-3-5 Project for Disciplines of Excellence of West China Hospital of Sichuan University/ ; GZC20241141//Postdoctoral Fellowship Program of CPSF/ ; },
mesh = {Humans ; *Ion Channels/metabolism ; Animals ; *Oligodendrocyte Precursor Cells/metabolism/pathology ; Oligodendroglia/metabolism ; Cell Differentiation ; },
abstract = {Oligodendrocyte precursor cells (OPCs) are a distinct and dynamic glial population that retain proliferative and migratory capacities throughout life. While traditionally recognized for differentiating into oligodendrocytes (OLs) and generating myelin to support rapid nerve conduction, OPCs are now increasingly appreciated for their diverse and non-canonical roles in the central nervous system (CNS), including direct interactions with neurons. A notable feature of OPCs is their expression of diverse ion channels that orchestrate essential cellular functions, including proliferation, migration, and differentiation. Given their widespread distribution across the CNS, OPCs are increasingly recognized as active contributors to the development and progression of various neurological disorders. This review aims to present a detailed summary of the physiological and pathological functions of ion channels in OPCs, emphasizing their contribution to CNS dysfunction. We further highlight recent advances suggesting that ion channels in OPCs may serve as promising therapeutic targets across a broad range of disorders, including, but not limited to, multiple sclerosis (MS), spinal cord injury, amyotrophic lateral sclerosis (ALS), psychiatric disorders, Alzheimer's disease (AD), and neuropathic pain (NP). Finally, we discuss emerging therapeutic strategies targeting OPC ion channel function, offering insights into potential future directions in the treatment of CNS diseases.},
}

Humans
*Ion Channels/metabolism
Animals
*Oligodendrocyte Precursor Cells/metabolism/pathology
Oligodendroglia/metabolism
Cell Differentiation

@article {pmid40806377,
year = {2025},
author = {Ghosh, M and Bayat, AH and Pearse, DD},
title = {Small Extracellular Vesicles in Neurodegenerative Disease: Emerging Roles in Pathogenesis, Biomarker Discovery, and Therapy.},
journal = {International journal of molecular sciences},
volume = {26},
number = {15},
pages = {},
pmid = {40806377},
issn = {1422-0067},
mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/therapy/metabolism/diagnosis/pathology/etiology ; Animals ; },
abstract = {Neurodegenerative diseases (NDDs) such as Alzheimer's, Parkinson's, ALS, and Huntington's pose a growing global challenge due to their complex pathobiology and aging demographics. Once considered as cellular debris, small extracellular vesicles (sEVs) are now recognized as active mediators of intercellular signaling in NDD progression. These nanovesicles (~30-150 nm), capable of crossing the blood-brain barrier, carry pathological proteins, RNAs, and lipids, facilitating the spread of toxic species like Aβ, tau, TDP-43, and α-synuclein. sEVs are increasingly recognized as valuable diagnostic tools, outperforming traditional CSF biomarkers in early detection and disease monitoring. On the therapeutic front, engineered sEVs offer a promising platform for CNS-targeted delivery of siRNAs, CRISPR tools, and neuroprotective agents, demonstrating efficacy in preclinical models. However, translational hurdles persist, including standardization, scalability, and regulatory alignment. Promising solutions are emerging, such as CRISPR-based barcoding, which enables high-resolution tracking of vesicle biodistribution; AI-guided analytics to enhance quality control; and coordinated regulatory efforts by the FDA, EMA, and ISEV aimed at unifying identity and purity criteria under forthcoming Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines. This review critically examines the mechanistic roles, diagnostic potential, and therapeutic applications of sEVs in NDDs, and outlines key strategies for clinical translation.},
}

Humans
*Extracellular Vesicles/metabolism
*Biomarkers/metabolism
*Neurodegenerative Diseases/therapy/metabolism/diagnosis/pathology/etiology
Animals

@article {pmid40806339,
year = {2025},
author = {Sonkodi, B},
title = {The Microbiota-Gut-Brain Axis in Light of the Brain Axes and Dysbiosis Where Piezo2 Is the Critical Initiating Player.},
journal = {International journal of molecular sciences},
volume = {26},
number = {15},
pages = {},
pmid = {40806339},
issn = {1422-0067},
mesh = {Humans ; *Ion Channels/metabolism ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/metabolism/microbiology ; Animals ; *Brain/metabolism ; Alzheimer Disease/metabolism ; Hippocampus/metabolism ; Circadian Rhythm ; },
abstract = {The current opinion paper puts into perspective how altered microbiota transplanted from Alzheimer's patients initiates the impairment of the microbiota-gut-brain axis of a healthy recipient, leading to impaired cognition primarily arising from the hippocampus, dysfunctional adult hippocampal neurogenesis, dysregulated systemic inflammation, long-term spatial memory impairment, or chronic pain with hippocampal involvement. This altered microbiota may induce acquired Piezo2 channelopathy on enterochromaffin cells, which, in turn, impairs the ultrafast long-range proton-based oscillatory synchronization to the hippocampus. Therefore, an intact microbiota-gut-brain axis could be responsible for the synchronization of ultradian and circadian rhythms, with the assistance of rhythmic bacteria within microbiota, to circadian regulation, and hippocampal learning and memory formation. Hippocampal ultradian clock encoding is proposed to be through a Piezo2-initiated proton-signaled manner via VGLUT3 allosteric transmission at a distance. Furthermore, this paper posits that these unaccounted-for ultrafast proton-based long-range oscillatory synchronizing ultradian axes may exist not only within the brain but also between the periphery and the brain in an analogous way, like in the case of this depicted microbiota-gut-brain axis. Accordingly, the irreversible Piezo2 channelopathy-induced loss of the Piezo2-initiated ultradian prefrontal-hippocampal axis leads to Alzheimer's disease pathophysiology onset. Moreover, the same irreversible microdamage-induced loss of the Piezo2-initiated ultradian muscle spindle-hippocampal and cerebellum-hippocampal axes may lead to amyotrophic lateral sclerosis and Parkinson's disease initiation, respectively.},
}

Humans
*Ion Channels/metabolism
*Gastrointestinal Microbiome/physiology
*Dysbiosis/metabolism/microbiology
Animals
*Brain/metabolism
Alzheimer Disease/metabolism
Hippocampus/metabolism
Circadian Rhythm

@article {pmid40802439,
year = {2025},
author = {Sousa, ES and Silva, LACD and Paiva, RM and Soares, KD and Azevedo, IC and Santos, VEP},
title = {Transitional Care for Patients with Amyotrophic Lateral Sclerosis to the Home: A Scoping Review.},
journal = {Revista brasileira de enfermagem},
volume = {78},
number = {3},
pages = {e20240297},
pmid = {40802439},
issn = {1984-0446},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/complications ; *Transitional Care/standards/trends ; *Home Care Services/trends/standards ; },
abstract = {OBJECTIVES: to map the care required for the transition of patients with Amyotrophic Lateral Sclerosis to the home environment.

METHODS: a scoping review was conducted following the JBI guidelines. The search for publications on the topic was carried out in databases such as PubMed and Web of Science between February and May 2023. Full-text studies that addressed the research objective were included. Letters to the editor, editorials, and opinion articles were excluded.

RESULTS: the final sample consisted of seven articles. Regarding care, the studies highlighted assistance with basic life needs, care planning, protocol development, the use of telehealth, and communication between healthcare services.

CONCLUSIONS: the care required for the transition of individuals with Amyotrophic Lateral Sclerosis to the home environment ranges from assistance with basic human needs to the coordination with other healthcare services. Altogether, these actions contribute to a safe and effective transitional process.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/complications
*Transitional Care/standards/trends
*Home Care Services/trends/standards

@article {pmid40801981,
year = {2025},
author = {Goleij, P and Amini, A and Sanaye, PM and Heidari, MM and Tabari, MAK and Aschner, M and Larsen, DS and Khan, H and Daglia, M},
title = {The IL-12 family cytokines in neurodegenerative diseases: dual roles in neurotoxicity and neuroprotection.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {40801981},
issn = {1568-5608},
abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and chronic neuroinflammation. Increasing evidence highlights the interleukin-12 (IL-12) cytokine family-including IL-12, IL-23, IL-27, and IL-35-as central regulators of immune responses in the central nervous system (CNS). IL-12 and IL-23 predominantly promote pro-inflammatory pathways by driving Th1/Th17 activity, microglial activation, and neurotoxicity, whereas IL-27 and IL-35 exert anti-inflammatory and neuroprotective effects through IL-10 induction and expansion of regulatory immune subsets. This review synthesizes disease-specific expression patterns and experimental findings, underscoring the dual pathogenic and protective roles of these cytokines. Therapeutic strategies targeting IL-12 family signaling have shown promise in preclinical and clinical contexts. In AD, blockade of IL-12/IL-23 reduced amyloid burden and improved cognition, while agents such as tadalafil and bergapten enhanced IL-27-mediated neuroprotection via PI3K/Akt, Wnt/β-catenin, and cGMP/PKG pathways. In MS, approaches including p40 blockade (ustekinumab, ABT-874), interferon-β therapy, hematopoietic stem cell transplantation, and B-cell depletion (ocrelizumab) variably suppressed IL-12/IL-23 and augmented IL-27/IL-35, influencing relapse rates and progression. Natural compounds such as curcumin, berberine, and vitamin D further highlight metabolic and dietary opportunities for cytokine modulation. In PD, combinatorial regimens combining herbal formulations with anti-inflammatory agents dampened IL-12-driven macrophage activation and supported dopaminergic neuron survival. Taken together, IL-12 family cytokines emerge as both biomarkers and therapeutic targets in NDs. However, context-dependent activity, blood-brain barrier constraints, and incomplete understanding-particularly of IL-35-pose translational challenges warranting further investigation.},
}

@article {pmid40801430,
year = {2025},
author = {Foster-Powell, A and Rostami-Hodjegan, A and Meno-Tetang, G and Mager, DE and Ogungbenro, K},
title = {Mathematical Modeling of Neuroinflammation in Neurodegenerative Diseases.},
journal = {CPT: pharmacometrics & systems pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1002/psp4.70064},
pmid = {40801430},
issn = {2163-8306},
support = {BB/W509930/1//Biotechnology and Biosciences Research Council (BBSRC) Industrial CASE studentship in collaboration with AstraZeneca (AZ), UK/ ; },
abstract = {Age-related neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD) are an increasing public health concern. Whereas the pathology of these diseases is complex, chronic central inflammation, or neuroinflammation, is commonly observed across many neurodegenerative diseases. Despite a huge wealth of resources and promising preclinical testing, effective disease-modifying therapies do not exist. This failure is owing to a combination of poor biological understanding of this response, unsuitable animal models, and poor scaling from pathway up to clinical levels. In order to address these challenges, systems-level mathematical models may be utilized. Here, we provide a background on neuroinflammation and summarize available mathematical models of this response. Models described by ordinary, partial, and delay differential equations, and Boolean logic are introduced and discussed. The results as discussed in this review suggest logic-based modeling as a formalism capable of managing the challenges associated with the modeling of CNS diseases.},
}

@article {pmid40799366,
year = {2025},
author = {Gao, B and Wang, L and Gong, J and Zhu, Z and Liu, Q and Yuan, H and Wang, H},
title = {The interplay between physical exercise and autophagy signaling in brain health, neurodegenerative diseases and aging.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1579208},
pmid = {40799366},
issn = {1663-4365},
abstract = {Brain health is increasingly recognized as a critical component of overall wellbeing, particularly concerning neurodegenerative diseases, which are characterized by the progressive degeneration of the nervous system. Conditions such as Alzheimer's disease (AD) and Parkinson's disease, together with less common disorders, resembling Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), significantly impact cognitive and physical health, affecting over 50 million individuals worldwide. This review explores the multifaceted relationship between brain health and neurodegeneration, emphasizing the roles of biological, environmental, and lifestyle factors. Notably, physical activity has been identified as a potent intervention that enhances neuroplasticity and metabolic resilience while mitigating the effects of neurodegeneration. Research indicates that exercise activates autophagy, which is crucial for clearing neurotoxic aggregates like amyloid-beta and α-synuclein, thereby promoting neuronal health. Additionally, exercise stimulates the production of neurotrophic factors such as BDNF and GDNF, which are essential for neuronal survival and function. Despite the promising findings regarding exercise as a preventive and therapeutic strategy for neurodegenerative diseases, further investigation into the underlying mechanisms is necessary to optimize these interventions. This review aims to elucidate the complex interactions between exercise, autophagy, and brain health to provide insights into effective strategies for combating neurodegeneration.},
}

@article {pmid40794238,
year = {2025},
author = {Jellinger, KA},
title = {Comorbid pathologies and their impact on progressive supranuclear palsy: current view.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {40794238},
issn = {1435-1463},
support = {Society for the Promotion of Research in Experimental Neurology, Vienna, Austria//Society for the Promotion of Research in Experimental Neurology, Vienna, Austria/ ; },
abstract = {Progressive supranuclear palsy, a four-repeat tauopathy, is clinically characterized by early postural instability and falls, vertical supranuclear palsy, levodopa poorly-responsive parkinsonism, pseudobulbar palsy, and cognitive impairment. It is morphologically featured by accumulation of hyperphosphorylated tau protein in neurons and glia predominantly in the basal ganglia, brainstem tegmentum and frontal cortex, associated with degeneration of the extrapyramidal system and cortical atrophy. Isolated PSP neuropathology is uncommon, with nearly 70% showing co-neuropathologies including Alzheimer-type, Lewy body, TDP-43 pathologies, argyrophilic grains, and other tauopathies and neurodegenerative disorders (Parkinson disease, amyotrophic lateral sclerosis). The most common comorbid conditions are hypertension, cardiovascular and cerebrovascular diseases, diabetes mellitus, polyneuropathies, muscular and urological disorders. Due the increased prevalence of comorbidities and their eminent impact on the progress and outcome of the disease, clinical trials should account for them in their design and selection. However, currently little is known about co-pathologies in these patients. In view of the eminent burden of comorbidities and resulting therapeutic consequences, the frequency of the different co-pathologies in PSP and their clinical impact will be discussed. It should provide insight into their pathogenic backgrounds as a basis for adequate treatment procedures to improve the quality of life of patients with this fatal disease.},
}

@article {pmid40787733,
year = {2025},
author = {Raaphorst, J and Gullick, NJ and Shokraneh, F and Brassington, R and Min, M and Ali, SS and Gordon, PA},
title = {Non-targeted immunosuppressive and immunomodulatory therapies for idiopathic inflammatory myopathies.},
journal = {The Cochrane database of systematic reviews},
volume = {8},
number = {8},
pages = {CD015855},
pmid = {40787733},
issn = {1469-493X},
mesh = {Humans ; *Myositis/drug therapy ; *Immunosuppressive Agents/therapeutic use/adverse effects ; Randomized Controlled Trials as Topic ; Dermatomyositis/drug therapy ; *Immunomodulating Agents/therapeutic use/adverse effects ; Bias ; Child ; Adult ; Polymyositis/drug therapy ; },
abstract = {BACKGROUND: Idiopathic inflammatory myopathies (IIM) are autoimmune-mediated inflammatory disorders of skeletal muscles with non-muscle involvement in some people, which carry significant morbidity and mortality. Treatment of IIM represents an area of unmet need. This review is an update of a review previously published in 2012, as new and promising data on non-targeted treatments have emerged.

OBJECTIVES: To assess the effects (benefits and harms) of non-targeted immunosuppressant and immunomodulatory treatments for IIM: dermatomyositis (DM, including juvenile dermatomyositis, jDM), immune-mediated necrotising myopathy (IMNM), anti-synthetase syndrome (ASS), overlap-myositis (OM) and polymyositis (PM). We also included cancer-related myositis and amyopathic dermatomyositis.

SEARCH METHODS: On 3 February 2023, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, Embase, MEDLINE, ClinicalTrials.gov and WHO ICTRP. We intended to check references and citations, and contact experts to identify additional studies, but lacked the resources.

SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs involving participants (adults and children) with IIM according to defined criteria. We included non-targeted immunosuppressants and immunomodulatory treatments alone or in combination, compared with a placebo, no treatment or another non-targeted immunosuppressant or immunomodulatory treatment. Our two primary outcomes were improvement of function or disability and improvement of muscle strength compared with baseline. By preference, we used the Health Assessment Questionnaire Disability Index (HAQ-DI) for disability and the Manual Muscle Test-8 (MMT8) score (adults or children) for muscle strength. Other outcomes were achievement of definitions of improvement (DOI) (the International Myositis Assessment and Clinical Studies (IMACS) Group or the more recent total improvement scores (TIS); for children, we reported achievement of improvement defined by the Paediatric Rheumatology International Trials Organisation (PRINTO)), cumulative corticosteroid dose, change in skin disease activity, serious adverse event and withdrawals for lack of benefit or adverse events.

DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias, we used the domain-based Cochrane risk of bias tool (RoB 1). We used fixed-effect models and, when needed, random-effects models for meta-analysis. We created summary of findings tables for any comparison for which data were available but prioritised comparisons of the following with placebo, no treatment or standard care: immunoglobulin, azathioprine and methotrexate. We included other comparisons as additional tables. We assessed the certainty of evidence using the GRADE approach.

MAIN RESULTS: We identified 16 studies (789 participants). The risk of bias in all but one study was high or unclear. Intravenous immunoglobulin (IVIg), compared to placebo, probably improves disability and muscle strength in participants with refractory IIM (standardised mean difference (SMD) 0.86, 95% confidence interval (CI) 0.51 to 1.21 (disability) and 0.78, 95% CI 0.43 to 1.13 (muscle strength); 3 RCTs, 136 participants; both moderate-certainty evidence). IVIg has a higher response rate based on American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria than placebo (risk ratio (RR) 1.80, 95% CI 1.26 to 2.56; 1 RCT, 95 participants; moderate-certainty evidence). IVIg, compared to placebo, improves skin symptoms (Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score 0 to 100; higher worse) in people with refractory DM (mean difference (MD) -8.20, 95% CI -11.91 to -4.49; 1 RCT, 95 participants; moderate-certainty evidence). There may be more serious adverse events with IVIg than with placebo (RR 1.91, 95% CI 0.50 to 7.30; 2 RCTs, 144 participants; very low-certainty evidence), but little or no difference between IVIg and placebo in withdrawals for either lack of benefit or adverse events (RR 1.02, 95% CI 0.24 to 4.33; 3 RCTs, 154 participants; very low-certainty evidence). For azathioprine versus placebo, one study showed little or no effect of azathioprine on improvement in muscle strength, but the evidence was very uncertain (RR 1.33, 95% CI 0.43 to 4.13; 1 RCT; 16 participants; very low-certainty evidence). The evidence was also very uncertain for cumulative steroid dose (MD 12.06 mg/kg, 95% CI -6.09 to 30.21; 1 RCT, 16 participants; very low-certainty evidence). This early study did not assess IMACS DOI or CDASI or measure function or disability. Serious adverse events and withdrawals for either lack of benefit or adverse events were not systematically reported. For methotrexate, there may be little or no improvement in adults with DM or PM in function (Amyotrophic Lateral Sclerosis Functional Rating Scale 0 to 40, higher better) (MD 1.24, 95% CI -1.60 to 4.08; 1 RCT, 27 participants; very low-certainty evidence), muscle strength (MMT scale 0 to 80, higher better) (MD -5.68, 95% CI -12.94 to 1.58; 1 RCT, 27 participants; very low-certainty evidence), achievement of IMACS DOI (RR 1.01, 95% CI 0.74 to 1.39; 1 RCT, 27 participants; very low-certainty evidence). Cumulative steroid dose was measured, but the data could not be analysed, and change in CDASI was not measured. In children with new-onset jDM on a background therapy of prednisone, a higher proportion may achieve minimal improvement according to the PRINTO criteria with methotrexate than with placebo (RR 1.40, 95% CI 1.01 to 1.96; 1 RCT, 93 participants; low-certainty evidence). Serious adverse events may occur slightly more frequently with methotrexate (RR 1.48, 95% CI 0.54 to 4.07; 2 RCTs, 124 participants; low-certainty evidence). There may be fewer withdrawals for lack of benefit or adverse events with methotrexate (RR 0.62, 95% CI 0.37 to 1.05; 3 RCTs, 151 participants; low-certainty evidence).

AUTHORS' CONCLUSIONS: Our review shows improvement in disability, muscle strength and skin symptoms following IVIg in people with refractory DM (for PM, these data are not reliable; other subtypes have not been investigated in RCTs). The improvements related to IVIg in DM may be clinically meaningful, but the absence of established minimal clinically important differences (MCIDs) for both disability and muscle strength in IIM does not facilitate interpretation. For the other agents, the small number of trials of immunosuppressive and immunomodulatory therapies is inadequate to decide whether these agents are beneficial in IIM (excluding IBM). Our review shows room for improvement in the conduct and reporting of clinical trials in IIM, as well as the need to further investigate MCIDs for important outcome measures in IIM.},
}

Humans
*Myositis/drug therapy
*Immunosuppressive Agents/therapeutic use/adverse effects
Randomized Controlled Trials as Topic
Dermatomyositis/drug therapy
*Immunomodulating Agents/therapeutic use/adverse effects
Bias
Child
Adult
Polymyositis/drug therapy

@article {pmid40787603,
year = {2025},
author = {Fonseca, I and Rueda, M and Cabanzo, C},
title = {The effect of dance interventions on well-being dimensions in older adults: a systematic review.},
journal = {Frontiers in sports and active living},
volume = {7},
number = {},
pages = {1594754},
pmid = {40787603},
issn = {2624-9367},
abstract = {BACKGROUND: Dance is increasingly recognized as a strategy that can support healthy aging. It incorporates physical, emotional, cognitive, and social engagement, which makes it particularly relevant for older populations. However, the effects of dance on multidimensional well-being have not yet been thoroughly synthesized.

OBJECTIVES: Systematically review empirical studies examining the effects of dance-based interventions on physical, emotional, cognitive, and social dimensions of well-being in older adults. We considered studies that assessed one or more of these dimensions as indicators of well-being.

DATA SOURCES: Studies were identified through database searches in Scopus, Web of Science, and SportDiscus conducted between October and November 2024.

Included studies were qualitative or quantitative empirical research published in peer-reviewed journals. Participants were adults aged 60 and older or identified as older adults. Interventions involved dance-based activities. Comparators included no intervention or alternative physical or recreational programs. The outcomes addressed at least one domain of well-being.

SYNTHESIS METHODS: This review followed the PRISMA 2020 guidelines. Eligibility criteria were defined using the PICOS framework. Study quality was assessed using Law et al.'s (1998) 16-item checklist. Due to methodological heterogeneity, a narrative synthesis was performed.

LIMITATIONS AND CONCLUSIONS: Although the results suggest that dance is a promising, low-cost intervention for promoting multidimensional well-being in older adults, several limitations should be noted. Many studies had small sample sizes or did not report effect sizes or randomization. Furthermore, some studies assessed only one or two dimensions of well-being rather than a multidimensional profile. This limits the scope of conclusions that can be drawn about integrated well-being. Future research should prioritize more rigorous designs, standardize multidimensional outcome measures, and assess long-term integrative effects to better inform health promotion policies.},
}

@article {pmid40784657,
year = {2025},
author = {Babcock, KJ and Abdolmohammadi, B and McKee, AC},
title = {Recent Advances in Chronic Traumatic Encephalopathy.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2025.07.008},
pmid = {40784657},
issn = {1525-2191},
abstract = {Exposure to repeated head impacts (RHIs), such as those experienced in contact sports or military service, can lead to the development of chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy. CTE cannot be diagnosed during life, only by post-mortem neuropathologic examination. The pathognomonic lesion of CTE consists of a perivascular accumulation of hyperphosphorylated tau as neurofibrillary tangles and dotlike neurites, preferentially at the depths of cortical sulci. The biomechanics of RHI involve acceleration, deceleration, and rotational forces that distort brain tissue and strain fragile structures, such as blood vessels and axons, especially in the crevices of the brain, where these forces are localized. CTE is unique from other tauopathies in its molecular structure, pattern, and regional distribution of tau. Studies in American football, rugby, and ice hockey players demonstrate a dose-response relationship between years of exposure to sport and increased CTE risk and severity. The clinical symptoms associated with CTE are classified as traumatic encephalopathy syndrome. Exposure to RHI also increases the deposition of other pathologic proteins, including β-amyloid, α-synuclein, and transactive response DNA-binding protein (TDP-43), raising the risk for other neurodegenerations, such as Alzheimer disease, Lewy body disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis.},
}

@article {pmid40782358,
year = {2025},
author = {St Clair-Sullivan, N and Brighton, LJ and Jha, P and Bone, AE and Sudirman, NA and Maddocks, M and Bayly, J},
title = {Assistive technologies for people with advanced disease and in palliative care: a scoping review.},
journal = {Disability and rehabilitation. Assistive technology},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17483107.2025.2536175},
pmid = {40782358},
issn = {1748-3115},
abstract = {Population ageing, multi-morbidity and associated disability is shifting global demand for health and care services. Innovative solutions are required to meet the evolving needs of people with advanced disease, support independent functioning and quality of life. This scoping review aimed to map and examine evidence on the role of assistive technology in adults with advanced disease and those receiving palliative care. A systematic search of Medline, Embase, PsychINFO and Cinahl, was conducted from inception to 31[st] July 2024 for studies investigating use of assistive technologies in people with advanced disease or receiving palliative care. Titles and abstracts were independently screened before full texts retrieved for eligibility review, data extraction, synthesis and descriptive analysis. 23/811 screened papers met eligibility criteria. Participants included ALS/MND (n13/23); palliative care (n4/23); cancer (n2/23); dementia (n2/23); Parkinson's (n1/23) and frailty (n1/23). Studies evaluated assistive technologies supporting ten functional domains; most frequently to support communication and information management (n13/23), least frequently orthoses and prosthesis, and domestic activities and participation in domestic life (n1/23). Outcomes of assistive technology use related to functioning, quality of life, dignity in end-of-life care and health service use. Implications for individual users, device design and delivery are discussed. This review highlights potential benefits of assistive technologies and gaps in research on their use for adults with advanced disease or receiving palliative care. Empirical evidence is limited and focuses on communication enhancing high-tech devices. Future research should explore assistive technology's impact over time on health outcomes, alongside strategies to integrate provision in care.},
}

@article {pmid40779613,
year = {2025},
author = {Chaouch, A and Crook, A and Douglas, AGL and McDermott, CJ and Al-Chalabi, A and McNeill, A and Bedford, J and Howard, J and MacLeod, R},
title = {The use of genetic testing in amyotrophic lateral sclerosis (ALS): a practical approach.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2025.2539895},
pmid = {40779613},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease thought to be precipitated by genetic, environment and lifestyle factors. In the UK, whole genome sequencing has become available to all people living with ALS, regardless of their family history or age of onset of disease. However, there is currently no formal guidance on how to deliver genetic counseling and testing in busy mainstream clinics. This article offers practical suggestions to clinicians who may wish or need to discuss genomic testing. As more clinical trials and targeted gene therapies develop, it is likely that conversations will evolve, reflecting the dynamic nature of this important and complex field.},
}

@article {pmid40779080,
year = {2025},
author = {Huo, X and Wang, L and Ma, J and Wu, Z and Wang, K},
title = {Bibliometric analysis of publication trends in meningioma research (1992 - 2023).},
journal = {Neurosurgical review},
volume = {48},
number = {1},
pages = {595},
pmid = {40779080},
issn = {1437-2320},
support = {2024-4-2048//Capital's Funds for Health Improvement and Research/ ; 2022YFE0112500//National Natural Science Foundation of China/ ; 62027813//National Natural Science Foundation of China,China/ ; YGLX202518//Beijing Hospitals Authority Clinical medicine Development of special funding support/ ; },
mesh = {*Meningioma ; *Bibliometrics ; Humans ; *Meningeal Neoplasms ; *Biomedical Research ; },
abstract = {The purpose of this study was providing an overview of meningioma research and its current situation. We conducted a bibliometric study of 14,027 articles and reviews on meningioma between January, 1992 to June, 2023 with the bibliometrix tool and VOSviewer. The distribution of authorship and collaboration patterns among countries, institutions, publications, and authors were analyzed. Core sources was analyzed with Bradford's law and author productivity was analyzed with Lotka's Law. The current situation and key areas were assessed through co-occurrence analysis. The number of publications has steadily increased over the years. The United States and University California San Francisco made the most contribution country and institution, respectively. Among the cited authors, Zhang J. emerged as the leading contributor while Perry A. was the most productive. Black P.M. had the highest h-index and Nassiri F. ranked first among the m-index. The most frequently cited study was Louis D.N. et al.'s 2016 publication in Acta Neuropathologica, titled "The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary." The journals with the most published articles and most cited publications were World Neurosurgery and Journal of Neurosurgery, respectively. According to keyword analysis, treatment option, chemotherapy, NF2 gene and estrogen receptor, and progesterone receptor are becoming more popular. This study provided a comprehensive overview of meningioma research, as well as potential future research fields, such as the chemotherapy and NF2 gene.},
}

*Meningioma
*Bibliometrics
Humans
*Meningeal Neoplasms
*Biomedical Research

@article {pmid40778304,
year = {2025},
author = {Zhang, K and Wen, M and Nan, X and Zhao, S and Li, H and Ai, Y and Zhu, H},
title = {NMDA receptors in neurodegenerative diseases: mechanisms and emerging therapeutic strategies.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1604378},
pmid = {40778304},
issn = {1663-4365},
abstract = {NMDA receptors (NMDARs) are widely distributed throughout the central nervous system (CNS) and play pivotal roles in normal physiological processes such as synaptic plasticity, learning, and memory. Substantial evidence indicates that NMDAR dysfunction, particularly excessive calcium influx, critically contributes to the pathogenesis of major neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Dysregulated glutamatergic signaling synergizes with pathological protein aggregation (e.g., Aβ, α-synuclein, mutant huntingtin) to drive neuronal loss. We systematically delineate NMDAR-related mechanisms underlying neurodegeneration, highlighting spatial-specific roles (e.g., synaptic NMDAR-mediated neuroprotection versus extrasynaptic NMDAR-mediated excitotoxicity) and crosstalk with mitochondrial dysfunction and oxidative stress. We critically evaluate current therapeutic strategies targeting NMDARs, including subunit-selective modulators, downstream effector modulation, and glutamate transporter modulation designed to restore NMDAR homeostasis. Consequently, NMDARs and their modulators represent promising therapeutic targets for these refractory conditions. This review comprehensively summarizes current research on the involvement of NMDARs and the glutamatergic system in neurodegenerative diseases. Furthermore, we discuss the clinical application of NMDAR-targeting agents and explore emerging therapeutic strategies focused on modulating NMDAR-related pathways. This article aims to provide a reference for elucidating the molecular mechanisms underlying these neurodegenerative disorders and to highlight potential avenues for future drug development.},
}

@article {pmid40775702,
year = {2025},
author = {Seckin, M and Tiwana, R and Fry, D and Bailey, C},
title = {Key themes and approaches in palliative and end-of-life care education for the general public: a systematic review.},
journal = {BMC palliative care},
volume = {24},
number = {1},
pages = {219},
pmid = {40775702},
issn = {1472-684X},
support = {2683473//NHS England/ ; 2683473//NHS England/ ; 2683473//NHS England/ ; 2683473//NHS England/ ; },
mesh = {Humans ; *Terminal Care/methods/standards ; *Palliative Care/methods/standards ; },
abstract = {BACKGROUND: Families, friends, and communities play a vital role in supporting individuals facing declining health, caregiving duties, loss, or grief, especially with the growing desire to die at home. The general public can significantly impact end-of-life care and offer essential support mechanisms. This review aimed to explore and identify key educational components related to palliative and end-of-life care for citizens, volunteers, and the general public.

METHODS: A mixed-method systematic review was conducted, incorporating four electronic databases (MEDLINE, PsycINFO, CINAHL, and the Cochrane Library) and grey literature searches, and quality was assessed using Hawker et al.'s (2002) critical appraisal checklists.

RESULTS: Twenty studies published between 2011 and 2023 were included, covering topics in palliative, end-of-life care, and bereavement education. These studies involved a total of 10,307 participants and identified 16 different educational programmes for the public, volunteers, and lay caregivers. The analysis revealed six main themes: foundational concepts and philosophies, communication and decision-making, planning and preparation, symptom management, end-of-life care practices, and caregiving support.

CONCLUSIONS: This review highlights the importance of training programmes to improve community involvement in caregiving and enhance the quality of care for individuals with life-limiting conditions. Expanding access to such educational resources can empower more people to contribute confidently to end-of-life care in their communities.

PROSPERO-ID: CRD42024533124.},
}

Humans
*Terminal Care/methods/standards
*Palliative Care/methods/standards

@article {pmid40774708,
year = {2025},
author = {Brown, KR and Quinton, ML and Tidmarsh, G and Cumming, J},
title = {Athletes' access to, attitudes towards and experiences of help-seeking for mental health: a scoping review.},
journal = {BMJ open},
volume = {15},
number = {8},
pages = {e097492},
pmid = {40774708},
issn = {2044-6055},
mesh = {Humans ; *Athletes/psychology ; *Patient Acceptance of Health Care/psychology ; *Mental Health ; *Mental Disorders/therapy/psychology ; *Help-Seeking Behavior ; *Mental Health Services ; *Health Services Accessibility ; },
abstract = {OBJECTIVES: Athletes have been found to experience a similar prevalence of mental health issues to non-athletes. However, they are subjected to a greater array of barriers to help-seeking for mental health, including sport-specific factors. This scoping review synthesised the literature on athletes' access to, attitudes towards and experiences of help-seeking for mental health from formal (mental health professionals such as psychiatrists) and semiformal sources (those who are not mental health professionals but are a service provider such as a coach).

DESIGN: The Joanna Briggs Institute framework and recommendations were used alongside the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocols checklist for scoping reviews. This scoping review was predominantly informed by Arksey and O'Malley's framework for scoping reviews, supplemented by Levac et al's additional recommendations. Rickwood and colleagues' help-seeking frameworks informed the research question, inclusion/exclusion criteria and analysis.

DATA SOURCES: The search terms and synonyms of "athlete" AND "mental health" AND "help-seeking" were searched in PsychINFO, Embase, MEDLINE, APA PsychArticles Full Text, Web of Science Core Collection, Scopus, Sport Discus, CINAHL and Proquest (Education Database, Health & Medical Collection, Nursing & Allied Health database, Psychology Database, Public Health Database, Education Collection, and Medicine & Education). These searches were conducted at three time points between April 2022 and 2024.

ELIGIBILITY CRITERIA: The inclusion and exclusion criteria were initially predetermined and specified in the protocol paper published in BMJ Open. Primary research articles, interventions and systematic reviews that referred to semiformal and formal sources of support were included.

DATA EXTRACTION AND SYNTHESIS: The lead reviewer (KRB) screened all titles and abstracts, and full texts, and extracted data from all included studies. A second reviewer was involved in screening and extracting 20%-30% of studies at each stage. Findings were synthesised descriptively (eg, study population, data collection method and location of studies) and by content (eg, access, attitudes and experiences, sources of support, use of theory and the validity of quantitative measures used).

RESULTS: After screening 4954 titles and abstracts and 275 full texts in Covidence, 104 papers were included in the review. This comprised of 87 primary research articles, 13 interventions and 4 systematic reviews. Most of the primary articles and interventions were published in the USA (50%). 49.4% of the primary articles used quantitative methods, 34.5% used qualitative methods and 16.1% used mixed methods. Attitudes towards mental health help-seeking were investigated in 78.8% of the included studies, experiences of help-seeking in 53.8% and access to sources of support in 31.7% of studies. Of the primary articles and interventions, formal sources were investigated in 55% of studies, semiformal sources in 2% and both in 26% of studies.

CONCLUSIONS: This scoping review of 104 papers showed the benefit of using help-seeking frameworks to shape and analyse a review. Analysing the results using these frameworks provided a novel contribution to the literature, showing where the athlete help-seeking literature base is currently focused and identified gaps for further research. For example, there is a need for further research on athletes in less developed nations, more qualitative and mixed methods studies, and further research on athletes' access to mental health support and their interactions with semiformal sources. The results have applied implications in public health and sport by highlighting the different factors that impact athlete help-seeking, and therefore areas where they require support.},
}

Humans
*Athletes/psychology
*Patient Acceptance of Health Care/psychology
*Mental Health
*Mental Disorders/therapy/psychology
*Help-Seeking Behavior
*Mental Health Services
*Health Services Accessibility

@article {pmid40757018,
year = {2025},
author = {Kato, N and Suzuki, R and Kaneko, H and Horimoto, Y},
title = {Effects of telerehabilitation on physical function and activities of daily living in patients with amyotrophic lateral sclerosis: a scoping review.},
journal = {Journal of physical therapy science},
volume = {37},
number = {8},
pages = {427-434},
pmid = {40757018},
issn = {0915-5287},
abstract = {[Purpose] This study aimed to clarify the effects of telerehabilitation on physical function and activities of daily living in patients with amyotrophic lateral sclerosis through a literature review. [Participants and Methods] We conducted a scoping review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews reporting guidelines. The PubMed, Scopus, Web of Science, and ProQuest databases were searched. Study design, type of interventions, telerehabilitation methods, adherence, effectiveness, adverse events, and patient satisfaction were extracted from the selected literature. [Results] Four case-series and one case-control study were identified. The interventions included respiratory muscle training (two studies), aerobic exercise, stretching, and comprehensive physical therapy (one study each). Various modalities were used, including videoconferencing, on-demand instructional videos, and real-time monitoring of vital signs using wearable devices. No serious adverse events were reported in any study. The dropout rate was 0-21%, and the compliance rate was 90%, indicating high adherence. Improvements in respiratory function and ADL were observed following respiratory rehabilitation. Patient satisfaction with telerehabilitation was high. [Conclusion] Telerehabilitation may improve adherence, respiratory function, and activities of daily living in patients with amyotrophic lateral sclerosis. However, its effects on other aspects of physical function remain unclear. Further high-quality studies are needed to establish evidence-based practices.},
}

@article {pmid40754996,
year = {2025},
author = {Stam, R},
title = {Low frequency magnetic field exposure and neurodegenerative disease: systematic review of animal studies.},
journal = {Electromagnetic biology and medicine},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/15368378.2025.2540435},
pmid = {40754996},
issn = {1536-8386},
abstract = {Epidemiological studies have found an association between occupational exposure to low frequency magnetic fields and the occurrence of motor neuron disease and Alzheimer's disease. No association has been found for Parkinson's disease and the evidence for multiple sclerosis is insufficient. Animal models studying the effects of low frequency magnetic fields on neurodegenerative disease induction or progression could provide more evidence on causation and the underlying mechanisms. A systematic search and review was conducted of peer-reviewed research articles involving animal experiments on the effects of low frequency magnetic field exposure on behavioural and neuroanatomical outcomes relevant for neurodegenerative diseases in humans. Firstly, experimental studies in naive animals do not support a causal relationship between exposure to low frequency magnetic fields and the induction of neuropathology relevant for Alzheimer's disease, but the number of studies relevant for motor neuron disease, multiple sclerosis and Parkinson's disease is too limited to draw conclusions. Secondly, experimental studies in existing animal models for neurodegenerative disease support a therapeutic (beneficial) effect of low frequency magnetic field treatment on behavioural and neuroanatomical abnormalities relevant for dementia (including Alzheimer's disease), multiple sclerosis and Parkinson's disease and no effect on disease progression in models relevant for motor neuron disease.},
}

@article {pmid40747386,
year = {2025},
author = {Arnold, WD and Castoro, R and Saxena, S},
title = {Innovations In Physical Medicine and Rehabilitation: Advances in the Diagnosis, Treatment, and Care of Amyotrophic Lateral Sclerosis.},
journal = {Missouri medicine},
volume = {122},
number = {3},
pages = {199-205},
pmid = {40747386},
issn = {0026-6620},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/therapy/rehabilitation ; *Physical and Rehabilitation Medicine/trends/methods ; Quality of Life ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that causes loss of upper and lower motor neurons, leading to muscle weakness and ultimately death. This review highlights recent advancements in Neuromuscular Medicine and Physical Medicine and Rehabilitation (PM&R), emphasizing innovations in the diagnosis, treatment, and care delivery for ALS. The field of PM&R emphasizes a multidisciplinary, patient-centered approach, incorporating advanced diagnostic tools, therapeutic strategies, adaptive equipment, and telerehabilitation to optimize function. Neuromuscular PM&R physicians play a key role in managing symptoms and maximizing functional independence. Current disease-modifying therapies include riluzole and edaravone which provide only modest benefits, but emerging gene therapies like tofersen for SOD1-related ALS offer promise for targeted treatment for genetic forms of ALS. Future advancements in regenerative therapies, biotechnologies, and digital health integration hold the potential to improve care and enhance the quality of life and functional independence of individuals living with ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/therapy/rehabilitation
*Physical and Rehabilitation Medicine/trends/methods
Quality of Life