Journal
PROTEIN AND PEPTIDE LETTERS
Volume 19, Issue 6, Pages 575-585Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986612800494020
Keywords
Proprotein convertase subtilisin Kexin9 (PCSK9); low density lipoprotein receptor; low density lipoprotein-cholesterol; hypercholesterolemia; cholesterol lowering agents; PCSK9 inhibitors
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Funding
- CIHR [MOP-69093]
- NSERC [238547]
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Proprotein Convertase Subtilisin Kexin9 (PCSK9), originally called Neural Apoptosis-Regulated Convertase1 (NARC1), is the latest member of mammalian subtilase super-family. Since its discovery in 2003, it has drawn significant attention because of its function in the degradation of Low Density Lipoprotein Receptor (LDL-R). LDL-R removes circulating LDL-cholesterol (LDL-C) in the blood. Increased level of PCSK9 functional activity will lead to an accumulation of cholesterol in the blood - a high risk factor for cardiovascular disease. This is confirmed by PCSK9 knock out and transgenic animals, various biochemical and clinical studies involving gain and loss of function genetic mutations of PCSK9 found in various subset of populations. Owing to this finding, development of strategies for inhibition of PCSK9 function has drawn significant research interest for therapeutic intervention of hypercholesterolemia. Thus PCSK9 is a target for the development of new cholesterol lowering drugs.
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