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Myelin produced by oligodendrocytes (OLs) acts as an electric insulator and assures proper conduction of information. Three major fractions of myelin lipids are cholesterol, phospholipids, and glycolipids. These lipids not only sculpt the myelin landscape as a structural support for proteins, but they also play a crucial role in molecular interactions underlying processes of protein trafficking and signal transductions. The high lipid content of myelin makes it susceptible to lipid metabolism disorders. Disorders in systemic and local lipid metabolism may lead to loss of myelin integrity and stability, and potentially to CNS demyelination seen in neurodegenerative diseases, notably progressive multiple sclerosis, for which there are few effective therapies. Precise interactions among disorders in lipid metabolism, function of oligodendrocytes, and demyelination\/remyelination events, including de novo myelin formation and myelin remodeling processes, may lay the foundation for novel therapeutics for progressive MS and other demyelinating CNS conditions.<\/jats:p>","DOI":"10.3390\/ijms26178314","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T09:31:12Z","timestamp":1756373472000},"page":"8314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Altered Lipid Metabolism in CNS Demyelination and Remyelination Are Key Elements Driving Progressive MS"],"prefix":"10.3390","volume":"26","author":[{"given":"Agata","family":"Matejuk","sequence":"first","affiliation":[{"name":"Department of Immunology, Collegium Medicum, University of Zielona G\u00f3ra, 65-417 Zielona G\u00f3ra, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szymon","family":"Matejuk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of South Alabama, 2451 University Hospital Dr., Mobile, AL 36617, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halina","family":"Offner","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research, R&D-31, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA"},{"name":"Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA"},{"name":"Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1207-6817","authenticated-orcid":false,"given":"Arthur A.","family":"Vandenbark","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research, R&D-31, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA"},{"name":"Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA"},{"name":"Department of Molecular Microbiology & Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","unstructured":"Tafti, D., Ehsan, M., and Xixis, K.L. 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