Niemann-Pick protein

Niemann-Pick disease C type 2 Gmj activator protein deficiency Sphingolipid activator protein deficiency... 

In the very rare and fatal Niemann-Pick Cl disease lysosomes in cells of the central nervous system and the viscera accumulate LDL-derived cholesterol. Study of the DNA of patients led to discovery of a 1278-residue integral membrane protein, which may be required for the Golgi-mediated transport of unest-erified cholesterol from lysosomes to the ER.189/232 234c... 

Field, F.J., Bom, E., and Mathur, S.N. 2004. Stanol esters decrease plasma cholesterol independently of intestinal ABC sterol transporters and Niemann-Pick Cl-like 1 protein gene expression. J. Lipid Res. 45, 2252-2259. 

Cholesterol is absorbed by intestinal epithelial cells via a Niemann-Pick Cl-Like 1 (NPCILI) protein. This is the target of a number of anti-hyperhpidaemic drugs used to lower cholesterol levels. Examples include miglustafi aUopregnanolone, oxysterols and cyclodextrins all are able to slow the progress of the disease, but none as yet provides an... 

Altmann SW, Davis HR Jr, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M, Wang L, Murgolo N, Graziano MP (2004) Niemann-Pick Cl Like 1 protein is critical for intestinal cholesterol absorption. Science 303 1201-1204... 

Choudhury A, Dominguez M, Puri V, et al. (2002) Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells. 1 Clin Invest 109 1541-1550... 

Davies, J., F. Chen, and Y. loannou. 2000. Transmembrane molecular pump activity of Niemann-Pick Cl protein. Science 290 2295-2298. 

Zhang, M., Sun, M., Dwyer, N. K., Comly, M. E., Patel, S. C., Sundaram, R., Hanover, J. A., and Blanchette-Mackie, E. J., Differential trafficking of the Niemann-Pick Cl and 2 proteins highlights distinct roles in late endocytic lipid trafficking, Acta Paediatr Suppl 92 (2003) 63-73. 

Liscum, L., Sturley, S.L. 2004. Intracellular trafficking of Niemann-Pick C proteins 1 and 2 obligate components of subcellular lipid transport. Biochim. Biophys. Acta 1685 22-27. 

Recent data indicate that ezetimibe inhibits a specific transport process in jejunal enterocytes, which take up cholesterol from the lumen. The putative transport protein is Niemann-Pick Cl-hke 1 protein (NPCILI). In wild-type mice, ezetimibe inhibits cholesterol absorption by about 70% in NPCILI knockout mice, cholesterol absorption is 86% lower than in wild-type mice, and ezetimibe has no effect on cholesterol absorption. Ezetimibe does not affect intestinal triglyceride absorption. In human subjects, ezetimibe reduced cholesterol absorption by 54%, precipitating a compensatory increase in cholesterol synthesis, which can be inhibited with a cholesterol synthesis inhibitor such as a statin. There is also a substantial reduction of plasma levels of plant sterols (campesterol and sitosterol concentrations are reduced by 48 and 41%, respectively), indicating that ezetimibe also inhibits intestinal absorption of plant sterols. 

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