期刊
ATHEROSCLEROSIS
卷 203, 期 1, 页码 1-7出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2008.06.010
关键词
Hypercholesterolemia; LDL receptor; PCSK9; Therapeutic target
The LDL receptor (LDLr) inhibitor Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) has emerged as a genetically validated target for lowering plasma LDL cholesterol levels. In 2007, PCSK9 was found to act as a chaperone that binds the LDLr, thereby targeting it for lysosomal degradation. The enzymatic activity of PCSK9 is not involved in that process, but rather permits proper intramolecular processing of PCSK9. This was demonstrated by both site directed mutagenesis and independent reports of the PCSK9 crystal structure. These reports also elucidated the mode of action of several naturally occurring mutants of PCSK9 associated with hyper- or hypocholesterolemia. The present review summarizes studies published or in print before May 2008 investigating the functional significance of PCSK9 and its promising aspects as a prognostic tool and a drug target. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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