Gasdermin家族蛋白介导的细胞焦亡及其病理作用与靶向干预  

Gasdermin-Mediated Pyroptosis and Its Pathological Roles and Targeted Intervention

作　　者：白杨 邓万燕 闵睿 刘星 BAI Yang;DENG Wanyan;MIN Rui;LIU Xing(The Center for Microbes,Development and Health,Institut Pasteur of Shanghai,Chinese Academy of Sciences,Shanghai 200031,China;University of Chinese Academy of Sciences,Beijing 100049,China;Shanghai Huashen Institute of Microbes and Infections,Shanghai 200052,China)

机构地区：[1]中国科学院上海巴斯德研究所微生物、发育与健康研究中心,上海200031 [2]中国科学院大学,北京100049 [3]上海华申微生物与感染研究所,上海200052

出　　处：《药学进展》2022年第8期603-616,共14页Progress in Pharmaceutical Sciences

基　　金：上海市市级科技重大专项资助的课题(No.HS2021SHZX001)。

摘　　要：细胞焦亡是一种程序性的炎性细胞死亡,关键执行分子是gasdermin家族蛋白。在细胞感知危险信号后,gasdermin发生剪切活化,释放出具有成孔活性的N端结构域,这一结构域与细胞膜磷脂结合并寡聚化形成稳定的膜孔洞结构,破坏细胞膜的完整性,并同时介导细胞向外界释放大量促炎细胞因子和危险信号。Gasdermin家族蛋白介导的细胞焦亡与促炎因子释放在感染、炎症相关疾病以及肿瘤中发挥了重要作用。综述介绍了gasdermin家族蛋白的激活与成孔机制,以及gasdermins在感染性疾病、炎症相关疾病与肿瘤中的作用,总结并展望了gasdermin家族蛋白作为多种疾病治疗靶标的潜力。Pyroptosis,a programmed inflammatory cell death,is executed by gasdermin family members.In response to danger signals,gasdermin is subjected to protease-mediated cleavage and activation,releasing its N-terminal domain with membrane pore-forming activity.N-terminal gasdermin binds to cell membrane phospholipids,and oligomerizes and forms stable membrane pore structures,causing loss of membrane integrity and secretion of pro-inflammatory cytokines and alarmins.Gasdermin-mediated pyroptosis and inflammatory responses play key roles in multiple biological processes including infection,inflammatory diseases as well as cancers.This review introduces the activation and pore-forming mechanisms of gasdermin family members and their roles in the above-mentioned diseases,and also highlights the therapeutic potentials in the treatment of related diseases by targeting gasdermins.

关 键 词：细胞焦亡 gasdermin 成孔机制 感染 炎症相关疾病 肿瘤 治疗靶标 

分 类 号：R363[医药卫生—病理学]