The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Cholesterol accumulation in NPC1-deficient neurons is ganglioside dependent.

Niemann-Pick type C (NPC) disease is a lysosomal disorder commonly caused by a recessive mutation in NPC1, which encodes an integral membrane protein with regions of homology to the morphogen receptor, Patched, and to 3-hydroxy-3-methylglutaryl coenzyme A reductase. Neurons in NPC disease exhibit extensive storage of free cholesterol and glycosphingolipids (GSLs), including GM2 and GM3 gangliosides. Most studies have viewed cholesterol storage as primary, with NPC1 functioning as a retroendocytic transporter for regulation of cholesterol homeostasis. Here, we analyze the effects of genetically depriving NPC neurons of complex gangliosides by creating mice doubly deficient in both NPC1 and the GSL synthetic enzyme, GM2/GD2 synthase (GalNAcT). Ganglioside and cholesterol expression in neurons of NPC1(-/-)/GalNAcT(+/+), NPC1(-/-)/GalNAcT(-/-), NPC1(+/+)/GalNAcT(-/-), and WT mice was examined in situ by immunocytochemical and histochemical methods. Neurons in double-deficient mice lacked intraneuronal GM2 accumulation as expected, but remarkably also exhibited absence or dramatic reduction in free cholesterol. Neurons storing cholesterol consistently showed GM3 accumulation but some GM3-positive neurons lacked cholesterol storage. These findings provide a compelling argument that cholesterol sequestration in NPC1-deficient neurons is ganglioside dependent and suggest that the function of NPC1 in these cells may be more closely linked to homeostatic control of GSLs than cholesterol.[1]


  1. Cholesterol accumulation in NPC1-deficient neurons is ganglioside dependent. Gondré-Lewis, M.C., McGlynn, R., Walkley, S.U. Curr. Biol. (2003) [Pubmed]
WikiGenes - Universities