Friday, 20 April 2012

PCSK9 : an attractive drug target for lowering LDL-C?

PCSK9 plays a major role in cholesterol metabolism through posttranslational down regulation of LDLR, the receptor responsible for clearing LDL-C from plasma.
PCSK9 (neural apoptosis-regulated convertase, NARC-1) is a 692-residue extracellular protein representing the 9th member of the secretory subtilase family expressed primarily in the kidneys, liver and intestines.

Genetic studies mapped PCSK9 along with LDLR and APOB to cause autosomal dominant hypercholesterolemia (ADH). Gain-of-function mutations increased plasma levels of low-density lipoprotein cholesterol (LDL-C), whereas nonsense or missense (loss-of-function) mutations, which interfere with folding or secretion of PCSK9, led to a reduction of plasma levels of LDL-C and an 88% decrease in the risk of coronary heart disease (CHD).
These findings led to a hypothesis that PCSK9 exerts its role in cholesterol metabolism through posttranslational down-regulation of LDLR, the receptor responsible for clearing plasma LDL-C. The hypothesis is consistent with a secreted form of PCSK9 bound directly to the first epidermal growth factor-like repeat (EGF-A) of LDLR and resulting in degradation of the receptor. PCSK9 appears to be an attractive drug target for lowering LDL-C.

PCSK9 Products:
CircuLex Human PCSK9 ELISA Kit - Product Code CY-8079
CircuLex Mouse/Rat PCSK9 ELISA Kit - Product Code CY-8078
CircuLex PCSK9-LDLR in vitro Binding Assay Kit - Product Code CY-8150


1. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, Basak A, Prat A, Chretien M (2003) Proc Natl Acad Sci USA 100:928
2. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, et al. (2003) Nat Genet 34:154
3. Leren TP (2004) Clin Genet 65:419
4. Allard D, Amsellem S, Abifadel M, Trillard M, Devillers M, Luc G, Krempf M, Reznik Y, Girardet JP, Fredenrich A, et al. (2005) Hum Mutat 26:497.
5. Cohen JC, Boerwinkle E, Mosley TH, Jr, Hobbs HH (2006) N Engl J Med 354, 1264
 6. Berge KE, Ose L, Leren TP (2006) Arterioscler Thromb Vasc Biol 26:1094
7. Maxwell KN, Breslow JL (2004) Proc Natl Acad Sci USA 101:7100
 8. Rashid S, Curtis DE, Garuti R, Anderson NN, Bashmakov Y, Ho YK, Hammer RE, Moon YA, Horton JD (2005) Proc Natl Acad Sci USA 102:5374
9. Lagace, T. A., Curtis, D. E., Garuti, R., McNutt, M. C., Park, S. W., Prather, H. B., Anderson, N. N., Ho, Y. K., Hammer, R. E., and Horton, J. D. (2006) J. Clin. Investig. 116, 2995
10. Cameron, J., Holla, O. L., Ranheim, T., Kulseth, M. A., Berge, K. E., and Leren, T. P. (2006) Hum. Mol. Genet. 15, 1551รข€“1558 11. Zhang, D. W., Lagace, T. A., Garuti, R., Zhao, Z., McDonald, M., Horton, J. D., Cohen, J. C., and Hobbs, H. H. (2007) J. Biol. Chem. 282, 18602

1 comment:

  1. A great and fantastic idea on attractive drug of lowering LDL-C.I’ll be learning about some of the features as I go along. I hope that it eventually proves easier for you the reader to follow the postings and comments.

    Mark Holland

    Iron Assay Kit


Webmaster: AnnWebCom | Site design: Creative Copyright 2005-2015 Caltag-Medsystems Limited - all rights reserved