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Journal of Inherited Metabolic Disease
Published in: Journal of Inherited Metabolic Disease 1/2015

01-01-2015 | Complex Lipids

Complex lipid trafficking in Niemann-Pick disease type C

Author: Marie T. Vanier

Published in: Journal of Inherited Metabolic Disease | Issue 1/2015

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Abstract

Niemann-Pick disease type C (NPC) is an atypical lysosomal storage disease resulting from mutations in one of two genes, either NPC1 or NPC2. Although a neurovisceral disorder, it is above all a neurodegenerative disease in the vast majority of patients. Not an enzyme deficiency, it is currently conceived as a lipid trafficking disorder. Impaired egress of cholesterol from the late endosomal/lysosomal (LE/L) compartment is a specific and key element of the pathogenesis, but other lipids, more specially sphingolipids, are also involved, and there are indications for further abnormalities. The full function of the NPC1 and NPC2 proteins is still unclear. This review provides a reappraisal of lipid storage and lysosomal enzymes activities in tissues/cells from NPC patients and animal models. It summarizes the current knowledge on the NPC1 and NPC2 proteins and their function in transport of cholesterol within the late endosomal-lysosomal compartment, with emphasis on differences between systemic organs and the brain; it also discusses regulation by membrane lipids of the NPC2-mediated cholesterol trafficking, interplay between cholesterol and sphingomyelin, the metabolic origin of glycosphingolipids stored in brain, and the putative role of free sphingoid bases in pathogenesis. Brief mention is finally made of diseases affecting other genes that were very recently shown to impact the "NPC pathway".
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Metadata
Title
Complex lipid trafficking in Niemann-Pick disease type C
Author
Marie T. Vanier
Publication date
01-01-2015
Publisher
Springer Netherlands
Published in
Journal of Inherited Metabolic Disease / Issue 1/2015
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI
https://doi.org/10.1007/s10545-014-9794-4

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