Cellular and Molecular Neurobiology最新文献

{"title":"Integrative Analysis Identifies PANoptosis-Associated Molecular Patterns and Immune Alterations in Rat Cerebral Ischemic-Reperfusion Injury.","authors":"Lu Li, Yu Wang, Huili Li, Ying Gao, Lan Luo, Sheng Wang, Mu Jin","doi":"10.1007/s10571-026-01714-w","DOIUrl":"10.1007/s10571-026-01714-w","url":null,"abstract":"<p><p>Cerebral ischemia-reperfusion (I/R) injury triggers a cascade of neuroinflammatory responses and multiple forms of regulated cell death. PANoptosis, integrating pyroptosis, apoptosis, and necroptosis, has been implicated in inflammatory disorders, but its role in cerebral I/R remains unclear. This study explored the molecular profile and immune relevance of PANoptosis-related genes (PRGs) in rat I/R injury. A rat I/R model was established by transient middle cerebral artery occlusion (MCAO). Transcriptome sequencing identified differentially expressed genes (DEGs) using DESeq2, and PANoptosis-related DEGs (PR-DEGs) were obtained by intersecting with GeneCards-derived PRGs. Functional enrichment (GO, KEGG, Metascape, GSEA), weighted gene co-expression network analysis (WGCNA), and immune infiltration analyses were performed to uncover biological functions and immune features associated with PR-DEGs. Rats subjected to I/R injury showed significant infarction, neurological deficits, and increased TNF-α, IL-1β, and IL-10 expression, along with downregulated Bcl-2 and upregulated CD16 and iNOS, indicating strong inflammatory responses. A total of 51 PR-DEGs were identified, primarily enriched in inflammatory and immune signaling pathways such as TNF, NF-κB, and MAPK. WGCNA revealed the salmon module as most correlated with I/R injury, and hub genes including CASP8, STAT3 were identified. Correlation and immune infiltration analyses demonstrated strong associations between key PR-DEGs and pro-inflammatory immune cells, suggesting a close relationship between PANoptosis-associated gene expression patterns and immune dysregulation in I/R injury. Our findings suggest coordinated activation of PANoptosis-related signaling in cerebral I/R injury. CASP8 and STAT3 were identified as key PR-DEGs associated with I/R, providing a foundation for further mechanistic investigation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13269598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Blood-Brain Barrier Disruption and Gut Microbiota Dysbiosis in Parkinson's Disease.","authors":"Wanyu Yao, Li Liu, Jiaxin Wang, Shanshan Chen, Chaofan Zhang, Ruiyi Liao, Yiwei Wang, Kunling Ou, Lirong Jiang, Yang Yu, Wei Dong","doi":"10.1007/s10571-026-01738-2","DOIUrl":"10.1007/s10571-026-01738-2","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a chronic neurodegenerative disorder primarily characterized by motor dysfunction. It is the second most prevalent neurodegenerative disorder after Alzheimer's disease. Its pathological manifestations include typical motor symptoms associated with Lewy bodies and loss of nigrostriatal dopaminergic neurons. Emerging evidence indicates that blood-brain barrier (BBB) dysfunction contributes to the onset and progression of PD. The BBB is essential for maintaining central nervous system (CNS) homeostasis by restricting the entry of circulating components and exogenous substances into the brain. In PD, disruption of BBB integrity facilitates the infiltration of circulating neurotoxins, macromolecules, and microorganisms, thereby triggering neuroinflammatory and immune responses. Furthermore, gut microbiota dysbiosis significantly impacts the integrity and function of the BBB via inflammatory mediators and metabolites, thus promoting PD progression. This study summarizes the associations between the BBB and gut microbiota with the onset and progression of PD and investigates the potential of enhancing BBB integrity and optimizing the gut microbiota as a theoretical foundation for developing novel therapeutic approaches for PD. Clinical trial number: not applicable.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13357484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the Neurovascular Unit Genetic Architecture of Early-Onset Ischemic Stroke: A Single-Cell Causal Framework for Target Discovery and Therapeutic Translation.","authors":"Qiu-Han Xu, Zhao-Hui Chai, Yu-Ning Zhang, Jian Shen","doi":"10.1007/s10571-026-01722-w","DOIUrl":"10.1007/s10571-026-01722-w","url":null,"abstract":"<p><p>BACKGROUND: The global incidence of early-onset ischemic stroke (EOS) is rising, with younger patients showing marked heterogeneity and lacking traditional risk factors, underscoring the role of undiscovered genetic determinants. The neurovascular unit (NVU) is central to cerebral homeostasis, yet whether its functional alterations contribute to ischemic stroke susceptibility remains unclear. Defining the NVU’s genetic architecture is therefore crucial for elucidating pathogenic mechanisms and advancing therapeutic discovery. METHODS: We integrated single-nucleus RNA-seq–based expression quantitative trait loci (eQTL) from healthy brain tissue with GWAS from the EOS Consortium. Mendelian randomization (MR), Bayesian colocalization, and Steiger filtering were applied to infer causal effects of NVU cell-type–specific gene expression on EOS. Cross-ancestry validation and PheWAS were conducted to assess robustness and pleiotropy. For translational insights, in silico drug screening, drug–disease MR, and molecular simulations were performed. RESULTS: MR analysis identified two NVU-resident genes—CYP4V2 in excitatory neurons and ANXA11 in astrocytes—as significantly associated with EOS. Both showed strong colocalization and consistent directionality, with cross-ancestry validation prioritizing CYP4V2 as a robust candidate. PheWAS revealed no major pleiotropic effects. Evidence from CYP4V2 knockout mice revealed neurological and metabolic abnormalities, supporting its biological relevance to ischemic stroke susceptibility. Combined drug screening, genetic evidence, and molecular stability analyses prioritized methotrexate as the most promising candidate. CONCLUSIONS: This study maps the genetic architecture of NVU cells and highlights their role in EOS susceptibility. We identified CYP4V2 as a causal gene and a pharmacologically tractable target. These findings provide a translational framework linking NVU dysfunction to ischemic stroke risk and inform future precision medicine strategies. </p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13247016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celf4 Regulates Excitability of Bushy Cells in the Cochlear Nucleus of the Mouse Brainstem.","authors":"Yige Li, Siyu Qiu, Fang Wang, Zhenghong Bi, Zhiyong Liu, Yingzi He, Geng-Lin Li","doi":"10.1007/s10571-026-01732-8","DOIUrl":"10.1007/s10571-026-01732-8","url":null,"abstract":"<p><p>The CUGBP Elav-like family 4 (CELF4), an RNA-binding protein, is dynamically expressed in spiral ganglion neurons (SGNs) in the cochlea over development, but how Celf4 is involved in regulating hearing functions is poorly understood. In this study, we generated a Celf4± mouse line and examined changes in the first two synapses along the auditory pathways. Firstly, we found that hearing functions were largely intact in Celf4± mice, with exception of reduced amplitude for Wave II of auditory brainstem responses (ABRs) and increased delays for Wave II and IV, both in case of 4 kHz only. Secondly, we found that counts of inner and outer hair cells (IHCs and OHCs) and SGNs remained unchanged in Celf4± mice, and that the number and function of ribbon synapses between IHCs and SGNs were comparable between WT and Celf4± mice. Lastly, function of the endbulb of Held synapse, formed between auditory nerve fibers (ANFs) of SGNs and bushy cells in the cochlear nucleus, was significantly altered in Celf4± mice. Specifically, synaptic vesicle release was subtly reduced, and excitability of bushy cells was significantly dampened, likely due to a hyperpolarized resting membrane potential. Furthermore, we found that spike kinetics was significantly faster in Celf4± bushy cells, likely caused by a larger fast-inactivating A-type potassium current (IA) found in these cells. In conclusion, we found that Celf4 haploinsufficiency altered transmission at the endbulb of Held synapses in the cochlear nucleus in a significant and multifaceted manner, revealing the roles of Celf4 in regulating hearing functions.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13243167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxic Alpha-Synuclein and the Opening of the Gate: Blood-Brain Barrier Damage and Stepwise Leukocyte Infiltration.","authors":"Piotr Wójcik, Carsten Culmsee, Agata Adamczyk","doi":"10.1007/s10571-026-01733-7","DOIUrl":"10.1007/s10571-026-01733-7","url":null,"abstract":"<p><p>α-Synucleinopathies are characterized by the pathological accumulation of misfolded α-synuclein (α-syn). In addition to its well-established neuronal toxicity, growing evidence suggests that α-syn may be associated with alterations in vascular and immune processes that contribute to neurodegeneration. Increasing attention has been directed toward the neurovascular unit and blood–brain barrier (BBB) as potential sites of early dysfunction, which may facilitate interactions between the central nervous system and peripheral immune compartments. However, the temporal sequence of these events and the relative contributions of specific immune cell populations remain incompletely defined. Experimental and clinical studies indicate that toxic α-syn species can affect endothelial and pericyte function, disrupt tight junction organization, and alter neurovascular signaling, potentially increasing BBB permeability. Such changes may allow the entry of peripheral immune cells into the brain parenchyma, where infiltrating lymphocytes—including Th1, Th17, and cytotoxic T cells—have been reported to contribute to neuroinflammatory responses through cytokine production, antigen-specific interactions, and modulation of microglial activity. In contrast, regulatory T cells may exert limited immunomodulatory effects, while monocytes and monocyte-derived macrophages appear capable of adopting either neurotoxic or neuroprotective phenotypes depending on the local inflammatory milieu. Emerging data further suggest that neutrophils and neutrophil extracellular traps (NETs) may participate in early vascular inflammation and BBB alterations, potentially influencing subsequent immune cell recruitment. Here, we review multiple, potentially complementary mechanisms that have been proposed to underlie BBB dysfunction and immune cell infiltration in α-synucleinopathies. By integrating neurovascular and immunological perspectives, this review aims to highlight the complex and dynamic interplay between vascular compromise and immune responses, and to discuss therapeutic strategies targeting the neurovascular unit and pathological immunity.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13243169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Small Chemical Compound Repsox Potentiates Oct4-Driven Astrocyte-to-Neural Stem Cell Reprogramming via Notch1/Hes1/Smurf2 Pathway.","authors":"Xiaoyu Ma, Zijian Liu, Yuqing He, Dandan Zhang, Peng Deng, Lin Li, Xin Li, Junping Li, Quanrui Ma, Hao Yang","doi":"10.1007/s10571-026-01731-9","DOIUrl":"10.1007/s10571-026-01731-9","url":null,"abstract":"<p><p>Central nervous system (CNS) injury is a prevalent and devastating neurological disorder characterized by progressive and irreversible neuronal loss, leading to persistent neurological deficits. Cell-replacement therapy using pluripotent neural stem cells (NSCs) offers considerable promise for treating CNS injury treatment. Our recent studies have demonstrated that mature astrocytes can be directly reprogrammed to a pluripotent state through specific stimuli. However, acquiring sufficient quantities of functional induced NSCs (iNSCs) derived from astrocytes for clinical applications remains challenging due to the low efficiency and instability in previous methodologies. Consequently, it is of critical importance to improve the reprogramming efficiency of astrocytes into iNSCs. In this study, we showed that the reprogramming of astrocytes into iNSCs via a single transcription factor Oct4 is significantly enhanced by continuous treatment with Repsox, a small molecule inhibitor of transforming growth factor-β (TGF-β) signaling. This enhancement was substantiated by increased efficiency in both reprogramming and conversion processes towards genuine NSCs, as demonstrated by the acquisition of distinctive hallmark NSC properties, including distinct morphological features, self-renewal capacity, expression of NSC-specific markers, and multipotency. Furthermore, the resulting iNSCs successfully differentiated into astrocytes, neurons, and oligodendrocytes. Notably, compared to iNSCs generated by Oct4 alone, Oct4/Repsox-induced NSCs exhibited a greater propensity to give rise to more neurons with neuronal functional properties, and relative fewer glial cells. Mechanistically, the activation of Notch1/Hes1/Smurf2 signaling cascades was involved in this enhanced intricate cell reprogramming events. The efficient reprogramming of astrocyte into iNSCs will provide a promising autologous cell-based therapeutic strategy for patients with CNS injury.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13243170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The AMPK-BECN1-System Xc⁻ Pathway in Traumatic Brain Injury: Implications for Exosome-Based Therapy.","authors":"Shenglin Yan, Weican Chen, Yuxin Huang, Nanying Jiang, Yibin Liu, Weifeng Liu","doi":"10.1007/s10571-026-01719-5","DOIUrl":"10.1007/s10571-026-01719-5","url":null,"abstract":"<p><p>Secondary neuronal death following traumatic brain injury (TBI) constitutes a central pathological mechanism driving permanent functional deficits. Mounting evidence reveals the “autophagy-ferroptosis axis,” forged by dysfunctional autophagy converging with activated ferroptosis, as a critical driver of this process. This review synthesizes current evidence on the molecular underpinnings of this axis within TBI, suggesting the AMPK (AMP-activated protein kinase)-BECN1 (beclin 1)-System Xc⁻ pathway as one potential core regulatory network. We provide an in-depth exploration of how this network may orchestrate neuronal fate through the “upstream decision-making” of the energy sensor AMPK, the “dual-function bridge” role of BECN1, and the “terminal executioner” function of System Xc⁻. Building upon this foundation, the review further advances an intervention hypothesis leveraging exosomes derived from olfactory ensheathing cells overexpressing brain-derived neurotrophic factor (BDNF-OE-OEC-Exos). We suggest their potential for TBI therapy, while acknowledging that this concept remains to be validated in relevant disease models and human studies.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13222926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuro-Behavioral Improvement and Mechanistic Pathways of Bone Marrow-Derived Mesenchymal Stem Cells and Exosomes in Experimental Multiple Sclerosis: A Systematic Review and Meta-analysis.","authors":"Hadis Kariminejad-Farsangi, Haniyeh Kariminejad-Farsangi, Meraj Sharifi, Saman Azh, Zahra Ghadery Nasab, Marzie Dehghan-Kuroki, Sara Joushi","doi":"10.1007/s10571-026-01715-9","DOIUrl":"10.1007/s10571-026-01715-9","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder with limited disease-modifying treatments. Bone marrow-derived mesenchymal stem cells (BM-MSCs) and their exosomes have emerged as promising therapeutic candidates due to their immunomodulatory and neuroprotective properties. This systematic review and meta-analysis evaluated the efficacy of BM-MSC and MSC-derived exosome therapy on clinical outcomes and mechanistic pathways in experimental autoimmune encephalomyelitis (EAE) models. A comprehensive search was conducted across PubMed, Web of Science, Scopus, Embase, ProQuest, and gray literature sources. In vivo studies investigating BM-MSC or MSC-exosome interventions in EAE models were included. Clinical score data were synthesized using random-effects models with standardized mean differences (SMD). Mechanistic outcomes included demyelination, GFAP and IBA1 expression, and inflammatory cytokines. Study quality was assessed using SYRCLE’s risk of bias tool, and publication bias was evaluated through funnel plots, Egger’s test, and trim-and-fill analysis. Sixty-one studies met inclusion criteria, with 48 included in the meta-analysis. BM-MSC treatment significantly improved clinical scores (SMD = –1.49, 95% CI: –1.86 to –1.11, I² = 84.31%, P = 0.00) and reduced demyelination (SMD = –2.96, 95% CI: –4.49 to –1.43, I² = 95.78%, P = 0.00). MSC therapy significantly decreased GFAP-positive astrocytes (SMD = –2.99, P = 0.03) and IBA1-positive microglia (SMD = –.82, P = 0.00). Furthermore, MSC treatment led to a significant reduction in TNF-α levels (SMD = –8.58, 95% CI: –6.23 to –0.92, P = 0.03). In contrast, effects on IL-10, IL-17, and IFN-γ levels were not statistically significant. MSC-derived exosomes showed a non-significant reduction in clinical scores (SMD = –3.14, 95% CI: –6.71 to 0.42, I² = 97.43%, P = 0.08). BM-MSC therapy demonstrates significant benefits in EAE models through immunomodulation and neuroprotection. While MSC-derived exosomes show potential, their effects require further validation. Future research should focus on standardized protocols, optimal dosing strategies, and mechanistic studies to facilitate clinical translation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13216409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Extracellular Vesicles (EVs)-Mediated Immune Dysregulation and Chronic Inflammation in Autism Spectrum Disorder.","authors":"Houda Yasmine Ali Moussa, Remy Thomas, Rawan Hussam Albatarni, Kyung Chul Shin, Wared Nour-Eldine, Fouad A Al-Shaban, Sara A Abdulla, Abeer R Al-Shammari, Julie Decock, Yongsoo Park","doi":"10.1007/s10571-026-01723-9","DOIUrl":"10.1007/s10571-026-01723-9","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by repetitive behaviors, communication deficits, and frequent comorbidities. While both genetic and environmental factors contribute to ASD etiology, immune dysregulation has emerged as a potential environmental driver, suggesting a critical role of chronic inflammation in ASD pathophysiology. We previously demonstrated that ASD individuals display specific changes in plasma EV cargo which is associated with immune dysregulation. Here, we show that ASD EVs contain dysregulated cytokine profiles, including Gro-α/CXCL1, RANTES/CCL5, IFN-γ, stem cell growth factor beta (SCGF-β), and IL-15. Notably, ASD EVs enhance IFN-γ secretion from peripheral blood lymphocytes (PBLs) in direct co-cultures, which can be reversed by treatment with the anti-inflammatory agent dexamethasone (Dex). Our findings suggest that ASD EVs contribute to chronic inflammation and highlight a potential therapeutic target for ASD intervention by mitigating ASD EV-induced chronic inflammation.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"46 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial-Immune Dysfunction in MS: Therapeutic Potential of EV-Mediated Transfer.","authors":"Parsa Navazi, Mohammad Fereidouni, Nafiseh Erfanian","doi":"10.1007/s10571-026-01716-8","DOIUrl":"10.1007/s10571-026-01716-8","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system. In this disease, mitochondrial dysfunction contributes to neurodegeneration, axonal loss, and progressive disability. Extracellular vesicle (EV)-mediated mitochondrial transfer has emerged as a promising cell-free strategy to restore mitochondrial homeostasis and modulate immune responses within the CNS. Preclinical studies, particularly in experimental autoimmune encephalomyelitis models, demonstrate that EV-based delivery of mitochondrial cargo improves cellular bioenergetics. In parallel, this approach reduces oxidative stress and neuroinflammation while supporting remyelination and neuroprotection. This review summarizes the mechanistic rationale, current preclinical evidence, and future translational perspectives of EV-mediated mitochondrial therapy in MS.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13216381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}