Molecular Neurobiology最新文献

{"title":"Nutritional Interventions in Amyotrophic Lateral Sclerosis: From Ketogenic Diet and Neuroprotective Nutrients to the Microbiota-Gut-Brain Axis Regulation.","authors":"Samira Nabakhteh, Anahita Lotfi, Arman Afsartaha, Elaheh Sadat Khodadadi, Siavash Abdolghaderi, Mozhdeh Mohammadpour, Yasaman Shokri, Pouria Kiani, Sajad Ehtiati, Sara Khakshournia, Seyyed Hossein Khatami","doi":"10.1007/s12035-025-04830-8","DOIUrl":"10.1007/s12035-025-04830-8","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with significant challenges in diagnosis and treatment. Recent research has highlighted the complex nature of ALS, encompassing behavioral impairments in addition to its neurological manifestations. While several medications have been approved to slow disease progression, ongoing research is focused on identifying new therapeutic targets. The current review focuses on emerging therapeutic strategies and personalized approaches aimed at improving patient outcomes. Recent advancements highlight the importance of targeting additional pathways such as mitochondrial dysfunction and neuroinflammation to develop more effective treatments. Personalized medicine, including genetic testing and biomarkers, is proving valuable in stratifying patients and tailoring treatment options. Complementary therapies, such as nutritional interventions like the ketogenic diet and microbiome modulation, also show promise. This review emphasizes the need for a multidisciplinary approach that integrates early diagnosis, targeted treatments, and supportive care to address the multisystemic nature of ALS and improve the quality of life for patients.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9216-9239"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustaining Brain Youth by Neural Stem Cells: Physiological and Therapeutic Perspectives.","authors":"Matilde Santos, João A Ferreira Moreira, Sónia Sá Santos, Susana Solá","doi":"10.1007/s12035-025-04774-z","DOIUrl":"10.1007/s12035-025-04774-z","url":null,"abstract":"<p><p>In the last two decades, stem cells (SCs) have attracted considerable interest for their research value and therapeutic potential in many fields, namely in neuroscience. On the other hand, the discovery of adult neurogenesis, the process by which new neurons are generated in the adult brain, challenged the traditional view that the brain is a static structure after development. The recent findings showing that adult neurogenesis has a significant role in brain plasticity, learning and memory, and emotional behavior, together with the fact that it is strongly dependent on several external and internal factors, have sparked more interest in this area. The mechanisms of adult neural stem cell (NSC) regulation, the physiological role of NSC-mediated neuroplasticity throughout life, and the most recent NSC-based therapeutic applications will be concisely reviewed. Noteworthy, due to their multipotency, self-renewal potential, and ability to secrete growth and immunomodulatory factors, NSCs have been mainly suggested for (1) transplantation, (2) neurotoxicology tests, and (3) drug screening approaches. The clinical trials of NSC-based therapy for different neurologic conditions are, nonetheless, mostly in the early phases and have not yet demonstrated conclusive efficacy or safety. Here, we provide an outlook of the major challenges and limitations, as well as some promising directions that could help to move toward stem cell widespread use in the treatment and prevention of several neurological disorders.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8222-8247"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes as Biomarkers and Therapeutic Agents in Neurodegenerative Diseases: Current Insights and Future Directions.","authors":"Sam Dehghani, Ozgecan Ocakcı, Pars Tan Hatipoglu, Veli Cengiz Özalp, Atakan Tevlek","doi":"10.1007/s12035-025-04825-5","DOIUrl":"10.1007/s12035-025-04825-5","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs) like Alzheimer's, Parkinson's, and ALS rank among the most challenging global health issues, marked by substantial obstacles in early diagnosis and effective treatment. Current diagnostic techniques frequently demonstrate inadequate sensitivity and specificity, whilst conventional treatment strategies encounter challenges related to restricted bioavailability and insufficient blood-brain barrier (BBB) permeability. Recently, exosomes-nanoscale vesicles packed with proteins, RNAs, and lipids-have emerged as promising agents with the potential to reshape diagnostic and therapeutic approaches to these diseases. Unlike conventional drug carriers, they naturally traverse the BBB and can deliver bioactive molecules to affected neural cells. Their molecular cargo can influence cell signaling, reduce neuroinflammation, and potentially slow neurodegenerative progression. Moreover, exosomes serve as non-invasive biomarkers, enabling early and precise diagnosis while allowing real-time disease monitoring. Additionally, engineered exosomes, loaded with therapeutic molecules, enhance this capability by targeting diseased neurons and overcoming conventional treatment barriers. By offering enhanced specificity, reduced immunogenicity, and an ability to bypass physiological limitations, exosome-based strategies present a transformative advantage over existing diagnostic and therapeutic approaches. This review examines the multifaceted role of exosomes in NDDs, emphasizing their diagnostic capabilities, intrinsic therapeutic functions, and transformative potential as advanced treatment vehicles.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9190-9215"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Clinical Model (SHACEA) for Post-stroke Cognitive Impairment Prognosis Occurred at Acute Phase and Last to 6 Months.","authors":"Nuo Ma, Yichen Zhao, Xiulin Meng, Yiming Huang, Jiangping Ma, Xueyuan Liu, Guilin Meng","doi":"10.1007/s12035-025-04783-y","DOIUrl":"10.1007/s12035-025-04783-y","url":null,"abstract":"<p><p>Post-stroke cognitive impairment (PSCI) leads to poor long-term stroke outcomes, severely increasing social and economic burdens. It is helpful to identify and intervene in PSCI in the early stage. This study intends to develop a new clinical risk score for identifying stroke survivors at significant risk of PSCI from the acute phase to 6 months of onset and to validate the new score using both internal and external cohorts. Analysis aiming to evaluate prognostic factors of acute-phase cognitive impairment lasting 6 months was carried out using two independent datasets, with one for model development and the other for validation. All enrolled patients completed baseline demographic, clinical, and imaging data collection and cognitive function scale assessment. The follow-up period was 6 months after the stroke, and interviews and cognitive function assessments were completed. A multivariate logistic regression analysis was performed, and the most important predictors were finally screened for modeling a prediction model. Six months post-stroke, 39.19% maintained PSCI in the development dataset. The final nine-point SHACEA (Stenosis, Hyperintensity, Age, Chronic cortical infarcts, Education, Atrophy) had an AUROC of 0.87 (95% CI 0.69-0.92) and was overall predictive of PSCI (LR χ² statistic of 89.34; p < 0.001). In the validation cohort, the SHACEA risk score was still relatively reliable in the validation cohort with an AUC of 0.74 (95% CI 0.71-0.80). The SHACEA risk score adequately identified acute stroke patients with cognitive impairment who are at an increased risk of developing PSCI after 6 months.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8475-8483"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving Insights into Prickle2 in Neurodevelopment and Neurological Disorders.","authors":"Yi Yang, Yanxia Mao, Yao Zhang, Tao Xiong","doi":"10.1007/s12035-025-04795-8","DOIUrl":"10.1007/s12035-025-04795-8","url":null,"abstract":"<p><p>The development of neural circuits is a complex, highly coordinated process crucial for the proper functioning of the nervous system. This process involves the intricate interplay of numerous genes and signaling pathways. Prickle2, a protein encoded by the planar cell polarity (PCP) genes, is a key component of the noncanonical Wnt/PCP signaling pathway and plays a critical role in neural circuit development. Recent studies have highlighted the essential functions of Prickle2 in various stages of neural circuit formation, including the development of the initial segment of neuronal axons, axon elongation and regeneration, dendrite formation, synapse formation, and vesicle transport. The normal expression and spatial distribution of Prickle2 are vital for these processes, and its dysregulation has been associated with several neurological disorders, including congenital neural tube defects, Alzheimer's disease, epilepsy, and autism spectrum disorders. This review aims to systematically summarize the upstream and downstream signaling pathways and regulatory interactions involving Prickle2 in neurodevelopment and neural circuit formation. By discussing the expression patterns of Prickle2 in neurodevelopment and its associations with neurological diseases, we provide insights into the mechanisms through which Prickle2 influences neurodevelopment and its potential implications in neurological disorders.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8540-8550"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of Pten Improves Huntington's Disease Phenotype by Reducing Htt Aggregates and Cell Death.","authors":"Nisha, Deepti Thapliyal, Bhavya Gohil, Aninda Sundar Modak, N Tarundas Singh, Chandramouli Mukherjee, Sanchi Ahuja, Bhavani Shankar Sahu, Mayanglambam Dhruba Singh","doi":"10.1007/s12035-025-04816-6","DOIUrl":"10.1007/s12035-025-04816-6","url":null,"abstract":"<p><p>Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder that stems from the expansion of CAG repeats within the coding region of Huntingtin (HTT) gene. Currently, there exists no effective therapeutic intervention that can prevent the progression of the disease. Our study aims to identify a novel genetic modifier with therapeutic potential. We employ transgenic flies containing HTT.ex1.Q93 and mRFP-HTT.588.Q138 constructs, which encode mutant pathogenic Huntingtin (Htt) proteins featuring 93 and 138 polyglutamine (Q) repeats respectively. The resultant mutant proteins cause the loss of photoreceptor neurons in the eye and a progressive loss of neuronal tissues in the brain and motor neurons in Drosophila. Several findings have demonstrated the association of HD with growth factor signaling defects. Phosphatase and tensin homolog (Pten) have been implicated in the negative regulation of the Insulin signaling/receptor tyrosine signaling pathway which regulates the growth and survival of cells. In the present study, we downregulated Pten and found a significant improvement in morphological phenotypes in the eye, brain, and motor neurons. These findings were further correlated with the enhancement of the functional vision and climbing ability of the flies. We also found the reduction in both Htt aggregate and caspase levels which are involved in the apoptotic pathway. In alignment with the genetic modulation of Pten, we elucidated the protective role of Pten inhibition through the utilization of VO-OHpic. VO-OHpic improved the climbing ability of flies and reduced the poly(Q) aggregates and apoptosis levels. A similar reduction in Htt aggregates was observed in the mouse neuronal inducible HD cell line model. Our study illustrates that Pten inhibition is a potential therapeutic approach for HD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8752-8767"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein E ε4-Specific Relationship Between Serum Olfactomedin 4 and Alzheimer's Disease.","authors":"Chunxiao Wei, Guimei Zhang, Xiaoshu Fu, Meng Zhao, Weijie Zhai, Yanxin Shen, Li Sun","doi":"10.1007/s12035-025-04812-w","DOIUrl":"10.1007/s12035-025-04812-w","url":null,"abstract":"<p><p>Olfactomedin 4 (OLFM4) plays important roles in inflammation, immune regulation, apoptosis, and neurodevelopment. This study aimed to investigate the correlation of serum OLFM4 with Alzheimer's disease (AD) and its clinical phenotype in different apolipoprotein E (APOE) ε4 status. Serum OLFM4 levels were measured in 122 AD patients and 113 healthy controls (HC). Correlations between OLFM4 levels and cognitive function and brain volume were analyzed in the context of APOE ε4 status. Multivariate logistic regression modeling was used to assess the contribution of high OLFM4 levels and APOE ε4 status to the risk of AD. It turns out that serum OLFM4 levels were significantly higher in patients with AD than in HC and were associated with APOE ε4 status but not sex. Serum OLFM4 levels showed a dose-response relationship with cognitive function and were correlated with brain atrophy. The combination of high OLFM4 levels and APOE ε4 expression was a risk factor for AD (odds ratio = 5.440; p = 0.017). In conclusion, serum OLFM4 may be involved in the pathology of AD and holds promise as a potential biomarker of AD as well as a therapeutic target. And the effects of OLFM4 for AD may be mediated by APOE ε4.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8900-8911"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilot Exploration of RGMa-BMP4 Signaling in Neutrophil Activation in NMOSD: Integrating Clinical and Molecular Insights.","authors":"Weihe Zhang, Lei Cui, Yeqiong Zhang, Yang He, Xiaoxuan Li, Yu Wang, Jinsong Jiao, Dantao Peng, Ming Jin, Cheng Xiao","doi":"10.1007/s12035-025-04840-6","DOIUrl":"10.1007/s12035-025-04840-6","url":null,"abstract":"<p><p>Neuromyelitis optica spectrum disorder (NMOSD) is a disabling autoimmune disease. Neutrophil activation plays a crucial role in the neuroinflammatory damage observed during disease exacerbations. This study aims to elucidate the potential role of the repulsive guidance molecule A-bone morphogenetic protein 4 (RGMa-BMP4) signaling pathway in neutrophil activation during NMOSD attacks. We employed transcriptomic sequencing, quantitative PCR, flow cytometry, and Western blot analysis on peripheral blood samples from NMOSD patients in acute and remission phases. Additionally, an NMO rat model was established to investigate in vivo molecular mechanisms, focusing on key signaling molecules, including RGMa, BMP4, and SMADs. Transcriptomic analysis identified five genes associated with NMOSD pathogenesis or neutrophil activation, with RGMA, EGFR, and HLA-DOB showing the most significant differences. RT-qPCR confirmed elevated levels of RGMA, BMP4, and SMADs in the acute phase. Flow cytometry and Western blotting demonstrated an increased nuclear-to-cytoplasmic ratio of SMAD4 protein in neutrophils from acute-phase NMOSD patients. In the NMO rat model, we observed significant upregulation of RGMA, BMP4, and SMAD4 mRNA in brain and spinal cord tissues, along with enhanced nuclear translocation of SMAD4 protein. Furthermore, there was a marked increase in myeloperoxidase (MPO) mRNA expression, a marker of neutrophil activation, in both brain and spinal cord tissues in the model group. Our findings indicate that the RGMa-BMP4 signaling pathway likely plays a key role in neutrophil-mediated neuroinflammation during NMOSD attacks. These results suggest potential therapeutic targets within this pathway, warranting further investigation into their clinical implications.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9151-9161"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insights on the Potential Role of Pyroptosis in Parkinson's Neuropathology and Therapeutic Targeting of NLRP3 Inflammasome with Recent Advances in Nanoparticle-Based miRNA Therapeutics.","authors":"Hebatallah M Saad, Esraa Atef, Abeer E Elsayed","doi":"10.1007/s12035-025-04818-4","DOIUrl":"10.1007/s12035-025-04818-4","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a widespread neurodegenerative disorder characterized by the gradual degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). This review aims to summarize the recent advancements in the pathophysiological mechanisms of pyroptosis, mediated by NLRP3 inflammasome, in advancing PD and the anti-pyroptotic agents that target NLRP3 inflammatory pathways and miRNA. PD pathophysiology is primarily linked to the aggregation of α-synuclein, the overproduction of reactive oxygen species (ROS), and the development of neuroinflammation due to microglial activation. Prior research indicated that a significant quantity of microglia is activated in both PD patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models, triggering neuroinflammation and resulting in a cascade of cellular death. Microglia possess an inflammatory complex pathway termed the nucleotide-binding oligomerization domain-, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome. Activation of the NLRP-3 inflammasome results in innate cytokines maturation, including IL-18 and IL-1β, which initiates the neuroinflammatory signal and induces a type of inflammatory cell death known as pyroptosis. Upon neuronal damage, intracellular levels of damage-associated molecular patterns (DAMPs), including reactive oxygen species (ROS), would build. DAMPs induce unregulated cell death and subsequent release of oxidative intermediates and pro-inflammatory cytokines, leading to the progression of PD. Thus, targeting of neuroinflammation using antipyroptotic medications can be efficiently achieved by blocking NLRP3 and obstructing IL-1β signaling and release. Furthermore, many research studies showed that miRNAs have been identified as regulators of the NLRP3 inflammasome and Nrf2 signal, which subsequently modulate the NLRP3-Nrf2 axis in PD. Nanotechnology promises potential for the advancement of miRNA-based therapies. Nanoparticles that ensure miRNA stability, traverse the blood-brain barrier (BBB) and distribute miRNA targeting regions needed to be created. In conclusion, targeting the pyroptosis pathway via NLRP3 or miRNA may serve as a prospective therapeutic strategy for PD in the future.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9365-9384"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal lncRNA RMRP-shuttled by Olfactory Mucosa-Mesenchymal Stem Cells Suppresses Microglial Pyroptosis to Improve Spinal Cord Injury via EIF4A3/SIRT1.","authors":"Chuang Wang, Jiangshan Zhang, Weiming Chen, Ling Gao, Jun He, Ying Xia","doi":"10.1007/s12035-025-04756-1","DOIUrl":"10.1007/s12035-025-04756-1","url":null,"abstract":"<p><p>Microglial pyroptosis significantly influences the pathological process and functional recovery after spinal cord injury (SCI). Olfactory mucosal mesenchymal stem cells (OM-MSCs) have shown remarkable therapeutic effects in SCI due to their neural substitution potential and paracrine mechanism. Therefore, the purpose of this study was to investigate the function and mechanism of OM-MSCs-derived exosomes (Exo) in regulating microglial pyroptosis after SCI. OM-MSCs and their secreted Exo were extracted and identified correspondingly. Microglia cells (HMC3) were stimulated by lipopolysaccharide (LPS) and co-cultured with Exo; the cell viability and pyroptosis of HMC3 cells were validated by CCK-8 and flow cytometry analysis. The inflammatory cytokines and pyroptosis-related proteins were measured by ELISA and western blot. Molecular interactions were verified by RNA immunoprecipitation and RNA pull-down. The SCI mouse model was constructed and administered with Exo, and then the histopathological features were detected using H&E, Nissl staining, and BMS score. lncRNA RMRP was enriched in OM-MSCs-Exo and downregulated in LPS-induced HMC3 cells. OM-MSCs-Exo administration markedly elevated lncRNA RMRP expression and repressed microglial pyroptosis in LPS-induced HMC3 cells, while these effects were diminished when lncRNA RMRP was depleted in OM-MSCs-Exo. Mechanistically, lncRNA RMRP maintained SIRT1 mRNA stability by recruiting EIF4A3. Overexpression of SIRT1 could rescue lncRNA RMRP knockdown-mediated microglia pyroptosis. In vivo data further supported that OM-MSCs-Exo administration relieves pyroptosis and nerve damage after SCI by carrying lncRNA RMRP. Our data suggested that exosomal lncRNA RMRP mitigated microglia pyroptosis and promoted motor function recovery after SCI by regulating the EIF4A3/SIRT1 axis.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8150-8165"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}