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Repurposing FDA\u2010approved drugs capable of promoting oligodendrocytes (OLs) differentiation represents a realistic and feasible approach for myelin repair and functional recovery. In this study, we report that ospemifene, an FDA\u2010approved selective estrogen receptor modulator (SERM), significantly promotes the differentiation of purified mouse oligodendrocyte precursor cells (OPCs) both in cultures and on nanofibers. In neonatal mice subjected to hypoxia, ospemifene prevented hypoxia\u2010induced myelin deficits in the developing central nervous system (CNS) and preserved neurofunctions in young adolescents, likely due to its promyelination potency. To assess the impact in demyelination models, we utilized the experimental autoimmune encephalomyelitis (EAE) mouse model, and ospemifene treatment alleviated functional deterioration in a dose\u2010dependent manner and benefited myelin regeneration. To confirm the effect on remyelination, toxin\u2010induced demyelination mice, injected with lysophosphatidylcholine into the corpus callosum, were treated with ospemifene. This treatment increased newly generated myelin sheaths in the lesions, confirming its promyelinogenesis effect. Together, our findings suggest that ospemifene is a promising treatment option for demyelinating diseases.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70235-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70235","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T09:50:57Z","timestamp":1758102657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ospemifene, a Selective Estrogen Receptor Modulator, Enhances Oligodendrocyte Myelination and Preserves Neurofunctions Against Injuries"],"prefix":"10.1111","volume":"169","author":[{"given":"Wei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery of Xinqiao Hospital Third Military Medical University  Chongqing China"},{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Emergence 5th People's Hospital of Chongqing  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junda","family":"Wang","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing 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