【摘 要】
：
Recent studies of human genetics and genome-wide screens have identified proprotein convertase subtilisin type 9 (PCSK9) as the third gene associated with a
【机 构】
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VA Palo Alto Health Care System USA
【出 处】
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中国上海第七届国际新药发明科技年会
论文部分内容阅读
Recent studies of human genetics and genome-wide screens have identified proprotein convertase subtilisin type 9 (PCSK9) as the third gene associated with autosomal dominant familial hypercholesterolemia,after LDL receptor (LDLR) and apoB100.PCSK9 functions as a natural inhibitor of LDLR that binds the extracellular domain of LDLR and triggers its intracellular degradation.PCSK9 and LDLR are coordinately regulated at the transcriptional level by sterols through their promoter-imbedded sterol response elements (SRE) and co-induced by statins.Identification of regulatory networks modulating PCSK9 transcription is important for developing selective repressors of PCSK9 to improve statin efficacy by prolonging the upregulation of LDLR.Interestingly,the plant-derived hypocholesterolemic compound berberine (BBR) upregulates LDLR expression while down regulating PCSK9.
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