{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:39:41Z","timestamp":1792172381454,"version":"4.4.0"},"reference-count":271,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Multiple sclerosis is a chronic, immune-mediated neurodegenerative disorder of the central nervous system, characterized by widespread demyelination, axonal injury, and progressive neurological impairment. The pathophysiology of multiple sclerosis involves complex interactions between immune cells and central nervous system resident cells, with oligodendrocytes (the myelin-producing glial cells) occupying a central role in both the disease\u2019s onset and progression. Oligodendrocyte dysfunction, including diminished regenerative capacity, heightened vulnerability to inflammatory cytokines, and increased susceptibility to oxidative stress, contributes significantly to the failure of remyelination observed in chronic multiple sclerosis lesions. Key factors such as microglial activation, T-cell-mediated cytotoxicity, and altered signaling pathways affecting oligodendrocyte progenitor cell maturation are explored in depth. Some therapeutic strategies under investigation encompass the use of pharmacological agents, cell-based interventions, and modulation of both the extracellular matrix and the immune microenvironment. Advancing our understanding of oligodendrocyte biology, along with the intrinsic and extrinsic factors that impede effective remyelination, is critical for the development of innovative, targeted therapies aimed at attenuating neurodegeneration and enhancing long-term clinical outcomes in patients with multiple sclerosis.<\/jats:p>","DOI":"10.3390\/cells14181408","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T19:16:17Z","timestamp":1757445377000},"page":"1408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["White Matter in Crisis: Oligodendrocytes and the Pathophysiology of Multiple Sclerosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Mario","family":"Garc\u00eda-Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Program of Immunology and Immunotherapy, CIMA-Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Department of Immunology and Immunotherapy, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37297","DOI":"10.1097\/MD.0000000000037297","article-title":"Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment","volume":"103","author":"Haki","year":"2024","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Coyle, P.K. 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