title: Lipids on trial: the search for the offending metabolite in Niemann-Pick type C disease.
abstract: Niemann-Pick disease type C is a complex lysosomal storage disorder caused by mutations in either the NPC1 or NPC2 genes that is characterized at the cellular level by the storage of multiple lipids, defective lysosomal calcium homeostasis and unique trafficking defects. We review the potential role of each of the individual storage lipids in initiating the pathogenic cascade and propose a model of NPC1 and NPC2 function based on the current knowledge.
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK. emyr.lloyd-evans@pharm.ox.ac.uk
authors.forename: Emyr
authors.initials: E
authors.lastname: Lloyd-Evans
authors.forename: Frances M
authors.initials: FM
authors.lastname: Platt
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000235:genetics / Q000378:metabolism*; D013110:Sphingosine / Q000378:metabolism*; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D006028:Glycosphingolipids; 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; D013110:Sphingosine