Cholesterol is an essential component of all cell membranes and particularly enriched in myelin membranes. Myelin membranes are a major target of immune attacks in the chronic neurological disorder multiple sclerosis (MS). During demyelinating insults, cholesterol is released from damaged myelin, increasing local levels of this unique lipid and impeding tissue regeneration. Here, we summarize the current knowledge of cholesterol-dependent processes during demyelination and remyelination, emphasizing cell type-specific responses. We discuss cellular lipid/ cholesterol metabolism during early and late disease phases and highlight the concept of lipid-based pharmacological interventions. We propose that knowledge of the interplay between cell type-specific cholesterol handling, inflammation, and blood-brain barrier (BBB) integrity will unravel disease processes and facilitate development of strategies for therapies to promote remyelination.
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