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Proprotein Convertase Subtilisin Kexin9 (PCSK9): A Novel Target For Cholesterol Regulation

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Abstract:

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.

Keywords: Hypercholesterolemia (ADH); PCSK9 inhibitors; Proprotein convertase subtilisin Kexin9 (PCSK9); cholesterol lowering agents; fluorogenic peptide; hypercholesterolemia; low density lipoprotein receptor; low density lipoproteincholesterol; lysosome compartments; trans Golgi network (TGN)

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986612800494020

Affiliations: Chronic Disease Program, Regional Protein Chemistry Center, Ottawa Hospital Research Institute, 725 Parkdale Avenue, Ottawa, ON K1Y 4E9, Canada.

Publication date: June 1, 2012

More about this publication?
  • Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.
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