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Integr. Neurosci."],"abstract":"<jats:p>Both myelination and remyelination in the central nervous system (CNS) rely on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). However, the microenvironment and underlying mechanisms of these two processes are significantly different. Myelination is driven by intrinsic developmental programs, whereas remyelination is triggered as a response to demyelinating injury. These distinct origins shape unique microenvironmental conditions that critically influence the respective processes. The microenvironment comprises, the extracellular matrix (ECM) and cellular components. Neurons, microglia, and astrocytes play stage-specific roles, ensuring proper myelin turnover under physiological conditions and regeneration after demyelination. Dysregulation of the microenvironment represents a critical driver of aberrant myelination and remyelination failure, as well as a key limitation of current pro-regenerative strategies. In this review, we discuss the cellular and molecular basis of microenvironmental regulation, recent advances in pathological microenvironmental alterations across demyelinating diseases (multiple sclerosis and neuromyelitis optica spectrum disorder) and myelin-associated disorders (Alzheimer\u2019s disease and ischemic stroke), and emerging pro-remyelination strategies targeting the microenvironment, such as Bruton\u2019s tyrosine kinase (BTK) inhibitors and microglia replacement strategies. We provide a non-cell autonomous perspective to advance the understanding of OLs differentiation and CNS remyelination.<\/jats:p>","DOI":"10.31083\/jin43257","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T08:26:51Z","timestamp":1780129611000},"source":"Crossref","is-referenced-by-count":0,"title":["Microenvironmental Regulation of Central Nervous System Myelination and Remyelination"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2055-7785","authenticated-orcid":true,"given":"Yuxuan","family":"Wang","sequence":"first","affiliation":[{"name":"Clinical Biobank Center, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 510280 Guangzhou, Guangdong, China"},{"name":"The Second School of Clinical Medicine, Southern Medical University, 510280 Guangzhou, Guangdong, China"},{"name":"Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, 510280 Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0879-1310","authenticated-orcid":true,"given":"Lingzhen","family":"Tan","sequence":"additional","affiliation":[{"name":"Clinical Biobank Center, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 510280 Guangzhou, Guangdong, China"},{"name":"The Second School of Clinical Medicine, Southern Medical University, 510280 Guangzhou, Guangdong, China"},{"name":"Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, 510280 Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9224-7702","authenticated-orcid":true,"given":"Lin","family":"Lao","sequence":"additional","affiliation":[{"name":"Clinical Biobank Center, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 510280 Guangzhou, Guangdong, China"},{"name":"The Second School of Clinical Medicine, Southern Medical University, 510280 Guangzhou, Guangdong, China"},{"name":"Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, 510280 Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0506-3114","authenticated-orcid":true,"given":"Xiaomeng","family":"Huang","sequence":"additional","affiliation":[{"name":"The Second School of Clinical Medicine, Southern Medical University, 510280 Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0692-8999","authenticated-orcid":true,"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515 Guangzhou, Guangdong, China"},{"name":"Department of Neurology, The Eighth Affiliated Hospital, The First People\u2019s Hospital of Shunde, Southern Medical University, 528300 Foshan, Guangdong, China"},{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, 510515 Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7925-9506","authenticated-orcid":true,"given":"Haitao","family":"Sun","sequence":"additional","affiliation":[{"name":"Clinical Biobank Center, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 510280 Guangzhou, Guangdong, China"},{"name":"Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, 510280 Guangzhou, Guangdong, China"},{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, 510515 Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Stadelmann C, Timmler S, Barrantes-Freer A, Simons M. 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