Niemann-Pick type C disease: molecular mechanisms and potential therapeutic approaches

J Neurochem. 2011 Mar;116(5):789-95. doi: 10.1111/j.1471-4159.2010.06976.x. Epub 2011 Jan 7.


Cholesterol is an important lipid of mammalian cells. Its unique physicochemical properties modulate membrane behavior and it serves as the precursor for steroid hormones, oxysterols and vitamin D. Cholesterol is effluxed from the late endosomes/lysosomes via the concerted action of at least two distinct proteins: Niemann-Pick C (NPC)1 and NPC2. Mutations in these two proteins manifest as NPC disease - a very rare, usually fatal, autosomal, recessive, neurovisceral, lysosomal storage disorder. In this review, we discuss the possible mechanisms of action for NPC1 and NPC2 in mediating cholesterol efflux, as well as the different therapeutic approaches being pursued for the treatment of this lipid storage disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cholesterol / metabolism
  • Cyclodextrins / therapeutic use
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Models, Biological
  • Molecular Chaperones / therapeutic use
  • Mutation / genetics
  • Niemann-Pick C1 Protein
  • Niemann-Pick Disease, Type C / genetics*
  • Niemann-Pick Disease, Type C / therapy*
  • Niemann-Pick Disease, Type C / urine*
  • Sphingomyelin Phosphodiesterase / therapeutic use
  • Vesicular Transport Proteins


  • Carrier Proteins
  • Cyclodextrins
  • Glycoproteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Molecular Chaperones
  • NPC1 protein, human
  • NPC2 protein, human
  • Niemann-Pick C1 Protein
  • Vesicular Transport Proteins
  • Cholesterol
  • acid sphingomyelinase-1
  • Sphingomyelin Phosphodiesterase