神经细胞凋亡调节转化酶-1在LDL胆固醇代谢中的作用

人类枯草溶菌素转化酶9(PCSK9)编码神经细胞凋亡调节转化酶-1,是一个属于丝氨酸蛋白酶K亚类的独特前蛋白转化酶。它能切割非碱性氨基酸,其底物特异性不同于许多其它前蛋白转化酶。它的唯一已知底物为前体NARC-1。PCSK9基因有多种序列变异,如错义突变S127R和F216L可引起常染色体显性高胆固醇血症;无义突变Y142X、C679X及错义变异R46L均可降低LDL胆固醇和冠心病发病率。通过研究这些变异和野生型PCSK9,发现PCSK9参与肝再生和神经分化,调节胆固醇代谢、含apoB脂蛋白代谢,并在动脉粥样硬化、冠心病等心血管疾病的发生发展和防治中发挥重要作用。

Effect of NARC-1 on Low Density Lipoprotein Cholesterol Metabolism

Proprotein convertase subtilisin/kexin type 9(PCSK9)encodes neural apoptosis-regulated convertase-1(NARC-1),which is a unique proprotein convertase related to the proteinase K subfamily of serine proteases.The specificity of its substrate is different from that of many other proprotein convertases in that it can cleave non-basic amino acids.Presently,the only known substrate of PCSK9 is itself.PCSK9 has many sequence variations.Several missense mutations(e.g.S127R and F216L)in PCSK9 are associated with an autosomal dominant form of hypercholesterolemia(ADH).Furthermore,nonsense mutations(e.g.Y142X and C679X)or new missense variants(e.g.R46L)have recently been found to be associated with a reduction in LDL cholesterol and to reduce the incidence of coronary heart disease(CHD).Further study of the wild-type or mutant PCSK9 showed that PCSK9 is not only related to liver regeneration and neuronal differentiation and regulates the metabolism of cholesterol and apoB-containing lipoproteins,but also plays an important role in the development and progression of atherosclerosis,CHD and other cardiovascular diseases.