Cellular pathology of Niemann-Pick type C disease.
Niemann-Pick type C (NPC) is a lysosomal storage disorder that results in the accumulation of cholesterol and sphingolipids. Mutations in the NPC1 or NPC2 gene are responsible for the disease but the precise functions of the encoded proteins remain unresolved. Recent observations have challenged the traditional concept of NPC as a primary cholesterol transport defect. This review updates the recent NPC literature, summarizing the increasing insight into the cholesterol trafficking circuits and also addressing the contribution of other lipids in the cellular pathogenesis. The importance of NPC as a model for subcellular lipid imbalance in studying more common diseases, such as Alzheimer's and cardiovascular diseases, is discussed.
Ikonen
Elina
E
Institute of Biotechnology, University of Helsinki, Helsinki, Finland. elina.ikonen@helsinki.fi
Hölttä-Vuori
Maarit
M
D002352:Carrier Proteins / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D004705:Endocytosis; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008562:Membrane Glycoproteins / Q000235:genetics; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; C104585:NPC2 protein, human; D000077296:Niemann-Pick C1 Protein; D033921:Vesicular Transport Proteins; D002784:Cholesterol