细胞焦亡的研究进展

Advance in research of pyroptosis

细胞焦亡是不同于细胞凋亡和细胞坏死特征的另外一种程序性细胞死亡方式,由Gasdermin蛋白介导发生。炎症小体激活后,活化的Caspase-1/4/5/11剪切激活GSDMD,释放的GSDMD N端片段重新折叠,并寡聚在细胞膜上形成直径10~15 nm的孔洞,促进了炎性物质的释放,并最终引起细胞溶胀死亡。除此之外,其他蛋白酶也能通过非炎症小体激活机制剪切激活Gasdermin家族蛋白介导细胞焦亡的发生。细胞焦亡近年来被广泛报道参与多种炎症性疾病的发生发展。本文就细胞焦亡的特征、分子机制、和疾病的关系以及靶向GSDMD的治疗策略进行综述。

Pyroptosis is another form of programmed cell death different from apoptosis and necrosis,which is executed by Gasdermin protein. Upon inflammasome activation,GSDMD is cleavaged by activated Caspase-1/4/5/11 and the released N-terminal fragment of GSDMD refolds and oligomerizes to form a hole with a diameter of 10~15 nm in the cell membrane,which promotes inflammatory substances release and cell swelling and death. In addition,other proteases can also cleave and activate Gasdermin proteins in an inflammasome independent way to mediate the occurrence of pyroptosis. Pyroptosis has been widely reported to participate in the occurrence and development of various inflammatory diseases. This article summarizes the characteristics of pyroptosis,molecular mechanism,and associated disease,as well as therapeutic strategies.