Myelin lipid metabolism and its role in myelination and myelin maintenance

Abstract

Myelin is a specialized cell membrane indispensable for rapid nerve conduction. The high abundance of membrane lipids is one of myelin’s salient features that contribute to its unique role as an insulator that electrically isolates nerve fibers across their myelinated surface. The most abundant lipids in myelin include cholesterol, glycosphingolipids, and plasmalogens, each playing critical roles in myelin development as well as function. This review serves to summarize the role of lipid metabolism in myelination and myelin maintenance, as well as the molecular determinants of myelin lipid homeostasis, with an emphasis on findings from genetic models. In addition, the implications of myelin lipid dysmetabolism in human diseases are highlighted in the context of hereditary leukodystrophies and neuropathies as well as acquired disorders such as Alzheimer’s disease. Public summary: • Myelin is an electrical insulator required for rapid nerve conduction. • Myelin is lipid-rich and has a unique lipid composition. • Disruption of lipid metabolism adversely affects myelin homeostasis. • Targeting lipid dysmetabolism could help address disease-associated myelin loss.