Niemann-Pick C disease: cholesterol handling gone awry.
Niemann-Pick C disease (NPC) is a debilitating, recessive disorder in humans that causes unrelenting neurological deterioration and is complicated by the presence of lipid-laden foamy cells in the major organs of the body. NPC fibroblasts cultured with an excess of low density lipoprotein (LDL) abnormally sequester cholesterol in their lysosomes. Biochemical analyses of NPC cells suggest an impairment in the intracellular transport of cholesterol to post-lysosomal destinations occurs in NPC. The recent identification of the NPC gene, NPC1, provides a definitive diagnosis of the disease and a means of studying this key component of intracellular cholesterol transport and homeostasis.
Morris
J A
JA
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Carstea
E D
ED
D000818:Animals; D002352:Carrier Proteins; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D005347:Fibroblasts; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D011506:Proteins; D002784:Cholesterol