Zhang Huayu, Xu Qian, Zhao Yimeng, He Naiqi, Ren Zhong, Xiang Qiong, Tang Zhihan, Liu Lushan
Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, Hunan Province 421001, P.R. China.
Curr Med Chem. 2024 Feb 16. doi: 10.2174/0109298673269288231123095215.
The proprotein convertase subtilisin/kexin type 9 (PCSK9) belongs to a member of the proprotein convertase (PC) family, which is mainly secreted by the liver and plays a central role in lipid metabolism. Furthermore, PCSK9 plays a multifunctional role in promoting the inflammatory response, inducing cell apoptosis and pyroptosis and affecting tumor homeostasis. The brain is the organ with the richest lipid content. Incidentally, PCSK9 increased in many brain diseases, including brain injury and Alzheimer's disease (AD). Consequently, the relationship between PCSK9 and brain diseases has attracted increasing research interest. Amyloid beta (Aβ) accumulation is the central and initial event in the pathogenesis of AD. This study focuses on the effects of PCSK9 on Aβ accumulation in the brain via multiple modalities to explore the potential role of PCSK9 in AD, which is characterized by progressive loss of brain cells by increasing Aβ accumulation. The study also explores the new mechanism by which PCSK9 is involved in the pathogenesis of AD, providing interesting and innovative guidance for the future of PCSK9-targeted therapy for AD.
前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）属于前蛋白转化酶（PC）家族成员，主要由肝脏分泌，在脂质代谢中起核心作用。此外，PCSK9在促进炎症反应、诱导细胞凋亡和焦亡以及影响肿瘤内环境稳定方面发挥着多功能作用。大脑是脂质含量最丰富的器官。顺便提一下，PCSK9在许多脑部疾病中都会升高，包括脑损伤和阿尔茨海默病（AD）。因此，PCSK9与脑部疾病之间的关系已引起越来越多的研究关注。β淀粉样蛋白（Aβ）的积累是AD发病机制的核心和起始事件。本研究通过多种方式聚焦于PCSK9对脑内Aβ积累的影响，以探索PCSK9在AD中的潜在作用，AD的特征是通过增加Aβ积累导致脑细胞进行性丧失。该研究还探索了PCSK9参与AD发病机制的新机制，为未来针对AD的PCSK9靶向治疗提供了有趣且创新的指导。
