Lipids on trial: the search for the offending metabolite in Niemann-Pick type C disease

Traffic. 2010 Apr;11(4):419-28. doi: 10.1111/j.1600-0854.2010.01032.x. Epub 2010 Jan 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cholesterol / metabolism*
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Glycosphingolipids / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lipid Metabolism
  • Lysosomes / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Niemann-Pick C1 Protein
  • Niemann-Pick Disease, Type C / genetics
  • Niemann-Pick Disease, Type C / metabolism*
  • Sphingosine / metabolism*
  • Vesicular Transport Proteins

Substances

  • Carrier Proteins
  • Glycoproteins
  • Glycosphingolipids
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • NPC1 protein, human
  • NPC2 protein, human
  • Niemann-Pick C1 Protein
  • Vesicular Transport Proteins
  • Cholesterol
  • Sphingosine