遗传 ›› 2020, Vol. 42 ›› Issue (10): 965-978.doi: 10.16288/j.yczz.20-065
收稿日期:
2020-04-06
修回日期:
2020-05-20
出版日期:
2020-10-20
发布日期:
2020-05-21
通讯作者:
王琰
E-mail:2017202040140@whu.edu.cn;Wang.y@whu.edu.cn
作者简介:
吴玉娴,在读硕士研究生,专业方向:生物化学与分子生物学。E-mail: 基金资助:
Received:
2020-04-06
Revised:
2020-05-20
Online:
2020-10-20
Published:
2020-05-21
Contact:
Wang Yan
E-mail:2017202040140@whu.edu.cn;Wang.y@whu.edu.cn
Supported by:
摘要:
血清低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)水平的升高是导致心血管疾病发生的主要危险因素。低密度脂蛋白受体(LDL receptor, LDLR)介导的低密度脂蛋白(low density lipoprotein, LDL)清除是决定循环中LDL-C水平的主要因素。LDL与细胞表面的LDLR结合后通过经典的网格蛋白小窝(clathrin-coated vesicles)内化进入细胞。在酸性核内体中,LDLR与LDL解离并循环回到细胞表面,释放的LDL将被运送到溶酶体中降解。前蛋白转化酶枯草溶菌素9 (proprotein convertase subtilisin kexin type 9, PCSK9)编码一种肝脏分泌型蛋白,其突变与LDL-C水平密切相关。前期研究已经证明,PCSK9直接与细胞表面的LDLR相互作用,二者一起通过网格蛋白小窝内化进入细胞。然而,在酸性核内体中,PCSK9和LDLR形成紧密的复合物,并进入溶酶体中进行降解,从而减少肝细胞表面LDLR的水平,降低肝脏对LDL-C的清除,该过程对于维持血浆中LDL在相对恒定的水平具有重要作用。因此,阻断PCSK9功能已成为治疗高胆固醇血症的新策略。本文综述了PCSK9的功能和机制研究的最新进展,并着重介绍了PCSK9抑制剂的研究进展,旨在为PCSK9-LDLR通路的研究和胆固醇代谢的调控提供参考。
吴玉娴, 王琰. PCSK9降解低密度脂蛋白受体分子机制研究进展[J]. 遗传, 2020, 42(10): 965-978.
Yuxian Wu, Yan Wang. Progress on the molecular mechanisms of PCSK9-mediated degradation of low density lipoprotein receptor[J]. Hereditas(Beijing), 2020, 42(10): 965-978.
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