Hao Wudi, Feng Cong
Department of Laboratory Medicine, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang 110004, China.
Laboratory of Research in Parkinson's Disease and Related Disorders, Health Science Institute, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
Neurobiol Dis. 2023 Oct 27:106333. doi: 10.1016/j.nbd.2023.106333.
Pyroptosis is an inflammatory and lysis type of programmed cell death. In the canonical pyroptosis signaling pathway, the NLRP3 inflammasome activates inflammatory caspase-1, which then shears cut the executor protein GSDMD. The N domains of GSDMD move to heterogeneous membranes, form pores, and release inflammatory cytokines IL-1β and IL-18, causing cell membrane swelling and rupture. Pyroptosis is mainly regulated by the key proteins in the signaling pathway, including inflammasome, caspase-1, GSDMD, IL-1β, and IL-18, as well as their agonists and inhibitors. Appropriate pyroptosis can improve host defense mechanisms, while excessive pyroptosis would derive pathological effects on central nervous system, leding to neuroinflammatory response, blood-brain barrier damage, and cognitive disfunction.
细胞焦亡是一种炎症性和裂解性的程序性细胞死亡。在经典的细胞焦亡信号通路中，NLRP3炎性小体激活炎性半胱天冬酶-1，然后其剪切执行者蛋白GSDMD。GSDMD的N结构域转移至异质膜，形成孔道，并释放炎性细胞因子IL-1β和IL-18，导致细胞膜肿胀和破裂。细胞焦亡主要受信号通路中的关键蛋白调控，包括炎性小体、半胱天冬酶-1、GSDMD、IL-1β和IL-18，以及它们的激动剂和抑制剂。适度的细胞焦亡可改善宿主防御机制，而过度的细胞焦亡会对中枢神经系统产生病理影响，导致神经炎症反应、血脑屏障损伤和认知功能障碍。
