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Extracellular vesicles (EVs) facilitate intercellular communication by mimicking the functions of their parent cells. In this study, we found that repeated administration of neural stem cell-derived extracellular vesicles (NSC-derived EVs) improved motor performance and provided protection to lumbar motor neurons, the neuromuscular junctions, and muscle morphology in the SOD1 G93A transgenic mouse model of ALS. Furthermore, by analyzing the RNA-sequencing of muscle specimens from ALS-SOD1 patients, we demonstrated that the rescue effects of NSC-derived EVs might be linked to the p53 pathway. Compared to the PBS control treatment group, both TP53 and the p53 upregulated modulator of apoptosis (PUMA) were downregulated in the spinal cord of mice treated with NSC-derived EVs. These data provide additional knowledge for the promising use of NSC-derived EVs as a potential therapy for ALS.<\/jats:p>","DOI":"10.1093\/jnen\/nlag013","type":"journal-article","created":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T12:36:14Z","timestamp":1770554174000},"page":"1239-1248","source":"Crossref","is-referenced-by-count":0,"title":["Neural stem cell\u2013derived small extracellular vesicles ameliorate disease progression in the SOD1 G93A murine model of amyotrophic lateral sclerosis"],"prefix":"10.1093","volume":"85","author":[{"given":"Yalan","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Neurology, Peking University First Hospital , Beijing, 100034,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital , Beijing, 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