PCSK9与多种代谢相关疾病发生发展关系的研究进展

Research advances in the relationship between PCSK9 and the occurrence and development of various metabolic diseases

前蛋白转化酶枯草溶菌素9(PCSK9)可以在细胞内外通过与低密度脂蛋白受体(LDLR)的相互作用影响LDLR的降解,在转录后水平调节LDLR从而影响血液中低密度脂蛋白胆固醇(LDL-C)的含量,已被验证是治疗心血管疾病的有效靶点,成为此类药物研发的热点之一。然而,随着人们对PCSK9生物学功能的进一步深入研究,发现它还参与了多种疾病的发生发展。本文总结了目前已发现的PCSK9在代谢性疾病(糖尿病、非酒精性脂肪肝)及与代谢密切相关的疾病(阿尔茨海默病、肿瘤)中的生物学功能,阐述PCSK9与这些疾病发生发展的关系,探讨该蛋白作为这些疾病治疗靶点的可能性。

Proprotein convertase subtilisin 9 (PCSK9) regulates degradation of LDLR via interacting with it at post-transcriptional levels in intracellular and extracellular microenvironments to affect the content of LDL-C in the blood. PCSK9 has been proven to be an effective target for the treatment of cardiovascular diseases and the development of PCSK9-tageting drugs have become one of the hot spots. However,along with the further study of the biological functions of PCSK9,it is found that PCSK9 is also involved in the occurrence and development of various diseases. This review article provides a comprehensive overview of the biological functions of PCSK9 in metabolic diseases (diabetes and nonalcoholic fatty liver disease) and metabolism-related diseases (Alzheimer’s disease and tumor),and the relationship between PCSK9 and the occurrence and development of these diseases,which might give some clues to discuss the possibility of PCSK9 as a therapeutic target of these diseases.