程序性坏死信号通路和炎症性疾病研究进展

Advances in the study of the signaling pathways of necroptosis and inflammatory diseases

程序性坏死(necroptosis)是半胱氨酸天冬氨酸蛋白酶(caspase)非依赖性细胞死亡模式,同细胞凋亡一样受细胞内信号途径的调控。受体相互作用蛋白激酶(receptor interaction protein kinase,RIP)1和3参与信号通路的调控,依次形成死亡诱导信号复合体、坏死复合体,促进程序性坏死的发生。这种细胞死亡模式在多种炎症性疾病的发生发展中起着非常重要的作用。

Necroptosis is a mechanism of cell death that is independent of caspase and that can be regulated by cellular signaling pathways just like apoptosis. Necroptosis can be initiated via many factors such as death receptors （DRs）, Toll- like receptors （TLRs）, and nucleotide binding and oligomerization domain-like receptors （NLRs）. Receptor interaction protein kinase 1 and receptor interaction protein kinase 3 regulate this signaling pathway. Necroptosis can be specifically inhibited by necrostatin-1. The formation of the death inducing signaling complex and the necrosome complex promote programmed cell death. Mixed lineage kinase domain-like protein a critical mediator of necroptosis. Necroptosis plays a major role （MLKL） is a component of the necrosome complex and in the pathogenesis of numerous inflammatory diseases.