Cholesterol in myelin biogenesis and hypomyelinating disorders.
The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids.
Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany. Electronic address: saher@em.mpg.de.
Gesine
G
Saher
Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany. Electronic address: stumpf@em.mpg.de.
Sina Kristin
SK
Stumpf
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D052556:Niemann-Pick Disease, Type C / Q000378:metabolism* / Q000473:pathology; D020371:Pelizaeus-Merzbacher Disease / Q000378:metabolism* / Q000473:pathology; D017933:Peripheral Nervous System / Q000166:cytology / Q000378:metabolism; D019082:Smith-Lemli-Opitz Syndrome / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission
D002784:Cholesterol
Cholesterol; Myelin; Niemann–Pick disease type C; Oligodendrocyte; Pelizaeus–Merzbacher disease; Smith–Lemli–Opitz syndrome