Disease relevance of NPC1

• Niemann-Pick type C (NPC) disease is a fatal autosomal-recessive neurodegenerative disorder characterized by the inappropriate accumulation of unesterified cholesterol in aberrant organelles [1].
• Niemann-Pick type C (NPC) is an autosomal recessive lysosomal storage disease [2].

High impact information on NPC1

• A Drosophila model of the Niemann-Pick type C lysosome storage disease: dnpc1a is required for molting and sterol homeostasis [1].
• A select group of compounds inhibits both Shh signaling, regulated by Ptc1, and late endosomal lipid sorting, regulated by the Ptc-related Niemann-Pick C1 (NPC1) protein [3].
• We show that, like NPC1-regulated lipid sorting, Shh signal transduction is blocked by antibodies that specifically disrupt the internal membranes of late endosomes, which provide a platform for protein and lipid sorting.CONCLUSIONS: These data support a model in which Ptc1 inhibits Smo only when in the same compartment [3].
• Fibroblasts from individuals with Niemann-Pick type C exhibit defective intracellular cholesterol transport [2].
• Mutations of a Drosophila NPC1 gene confer sterol and ecdysone metabolic defects [4].

Biological context of NPC1

• The recessive lethal phenotype of NPC1a mutants can be partially rescued on a diet of high cholesterol or one that includes the insect steroid hormone 20-hydroxyecdysone [4].

Associations of NPC1 with chemical compounds

• We also find that expression of NPC1a in the ring gland is sufficient to rescue the lethality associated with the loss of NPC1a and that cholesterol levels in NPC1a mutant larvae are unchanged relative to controls [4].

References