Niemann-Pick C1 Disease Gene: Homology to Mediators of Cholesterol Homeostasis
Open Access
- 11 July 1997
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 277 (5323), 228-231
- https://doi.org/10.1126/science.277.5323.228
Abstract
Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)–derived cholesterol. By positional cloning methods, a gene (NPC1)with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-typeNPC1cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking. The 1278–amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.Keywords
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