Lipid and cholesterol trafficking in NPC

Biochim Biophys Acta. 2004 Oct 11;1685(1-3):28-37. doi: 10.1016/j.bbalip.2004.08.009.

Abstract

Niemann-Pick type C, or NPC for short, is an early childhood disease exhibiting progressive neurological degeneration, associated with hepatosplenomegaly in some cases. The disease, at the cellular level, is a result of improper trafficking of lipids such as cholesterol and glycosphingolipids (GSLs) to lysosome-like storage organelles (LSOs), which become engorged with these lipids. It is believed that the initial defect in trafficking, whether of cholesterol or a GSL, results in an eventual traffic jam in these LSOs. This leads to the retention of not only other lipids, but also of transmembrane proteins that transiently associate with the late endosomes (LE) in normal cells, on their way to other cellular destinations such as the trans-Golgi network (TGN). In this review, we discuss the biophysical properties of lipids and cholesterol that might determine their intracellular itineraries, and how these itineraries are altered in NPC cells, which have defects in the proteins NPC1 or NPC2. We also discuss some potential therapeutic directions being suggested by recent research.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Biophysical Phenomena
  • Biophysics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cholesterol / metabolism*
  • Endocytosis
  • Endoplasmic Reticulum / metabolism
  • Endosomes / metabolism
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Humans
  • Lipid Metabolism*
  • Lysosomes / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Models, Biological
  • Niemann-Pick Diseases / drug therapy
  • Niemann-Pick Diseases / etiology
  • Niemann-Pick Diseases / metabolism*
  • Niemann-Pick Diseases / pathology

Substances

  • Carrier Proteins
  • Glycoproteins
  • Membrane Glycoproteins
  • NPC1 protein, human
  • NPC2 protein, human
  • Cholesterol