Lipid imbalance in the neurological disorder, Niemann-Pick C disease

Vance, Jean E.

doi:10.1016/j.febslet.2006.06.008

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Volume 580, Issue 23 , Pages 5518-5524, 9 October 2006

Lipid imbalance in the neurological disorder, Niemann-Pick C disease

Edited by Gerrit van Meer

Canadian Institutes for Health Research Group on the Molecular and Cell Biology of Lipids, Department of Medicine, 332 HMRC, University of Alberta, Edmonton, Alta., Canada T6G 2S2

Received 11 May 2006; received in revised form 29 May 2006; accepted 1 June 2006. published online 15 June 2006.

Abstract

Niemann-Pick C (NPC) disease is a progressive neurological disorder in which cholesterol, gangliosides and bis-monoacylglycerol phosphate accumulate in late endosomes/lysosomes. This disease is caused by mutations in either the NPC1 or NPC2 gene. NPC1 and NPC2 are involved in egress of lipids, particularly cholesterol, from late endosomes/lysosomes but the precise functions of these proteins are not clear. An important question regarding the function of NPC proteins is: why do mutations in these ubiquitously expressed proteins have such dire consequences in the brain? This review summarizes the roles of NPC proteins in lipid homeostasis particularly in the central nervous system.

Keywords: Cholesterol, Neurodegeneration, Gangliosides, Late endosomes, Lysosomes