The pathophysiology and mechanisms of NP-C disease.
The molecular isolation of NPC1 and NPC2, the genes defective in patients with Niemann-Pick disease type C (NP-C), has heralded in an exponential increase in our understanding of this syndrome and thus of human intracellular sterol transport. Despite this, neither the mechanisms of action nor the substrates for these putative transporters have been defined. In this overview, we describe our perspectives on the current awareness of the genetic determination and cellular biology of this syndrome, with emphasis on the underlying events that lead to neurodegeneration and the manner in which they might eventually be treated.
Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032, USA. sls37@columbia.edu
Stephen L
SL
Sturley
Marc C
MC
Patterson
William
W
Balch
Laura
L
Liscum
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism; D005544:Forecasting; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology* / Q000628:therapy; D013107:Sphingolipids / Q000235:genetics / Q000378:metabolism; 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; D013107:Sphingolipids; D033921:Vesicular Transport Proteins; D002784:Cholesterol