In this review, we will mainly summarize the molecular characteristics and biological significance of NPC2, highlighting its vital roles in NPC disease.
Because neurodegeneration is the main clinical feature of NPC disease, and FTY720 accumulates in the CNS and has several advantages over available histone deacetylase inhibitors now in clinical trials, our work provides a potential opportunity for treatment of this incurable disease.-Newton, J., Hait, N. C., Maceyka, M., Colaco, A., Maczis, M., Wassif, C. A., Cougnoux, A., Porter, F. D., Milstien, S., Platt, N., Platt, F. M., Spiegel, S. FTY720/fingolimod increases NPC1 and NPC2 expression and reduces cholesterol and sphingolipid accumulation in Niemann-Pick type C mutant fibroblasts.
Impaired function of NPC1 or NPC2 lysosomal proteins leads to the intracellular accumulation of unesterified cholesterol, the primary defect underlying Niemann-Pick type C (NPC) disease.
Mutations in the NPC1 or NPC2 genes lead to Niemann-Pick type C (NPC) disease, a rare lysosomal storage disorder characterized by progressive neurodegeneration.
Niemann-Pick type C (NPC) disease is a lysosomal storage disease in which endocytosed cholesterol becomes sequestered in late endosomes/lysosomes (LEs/Ls) because of mutations in either the NPC1 or NPC2 gene.
The Niemann-Pick type C (NPC) disease is characterized by accumulation of lipids within the late endosome/lysosome (LE/LY) compartment as a result of dysfunctions of the NPC1 or NPC2 proteins and an altered distribution and/or functioning of proteins involved in the regulation of membrane dynamics.
Genetic deficiency of NPC1 or NPC2 results in a devastating cholesterol-glycosphingolipidosis of brain and other organs known as Niemann-Pick type C (NPC) disease.
This review provides a detailed examination of NPC1 and HE1/NPC2 in regulating the transport of cholesterol through the late endosomal/lysosomal system to other cellular compartments responsible for maintaining intracellular cholesterol homeostasis, and how defective function of these proteins may be responsible for the pathophysiology associated with NPC disease.