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Abstract

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 demye-
linating 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 con-
cept 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.