细胞焦亡效应蛋白的作用机制及相关疾病的研究进展

Recent progress in mechanisms of major effector proteins for pyroptosis and the related diseases

细胞焦亡是一种促炎的程序性细胞死亡方式,并同时具有凋亡和坏死的特点。Toll样受体(Toll like receptors,TLRs)可以感受及识别不同的刺激,并传递信号至依赖半胱氨酸天冬氨酸酶-1(caspase-1)的经典焦亡途径或依赖半胱氨酸天冬氨酸酶-11(caspase-11)的非经典焦亡途径。炎性体在激活信号下的装配是诱导焦亡途径的核心环节,其中NLRP3炎性体是目前研究最多的,是其典型代表。激活的炎性体可以活化炎性caspases,后者进一步促进白细胞介素-1β/18(IL-1β/18)的成熟和释放。焦亡的执行蛋白GSDMD可以在细胞膜上形成膜孔,最终导致细胞渗透溶胀和裂解,同时将炎症因子释放到细胞外,进一步加重炎症反应。

Pyroptosis is a pro-inflammatory type of programmed cell death, has features of both apoptosis and necrosis. TLRs family can sense different stimuli of PAMPs and DAMPs, and transmit the signaling for pyroptosis, depending on caspase-l-dependent canonical pathways and caspase-ll-dependent noneanonical pathways. The specific inflammasome in each pathway assembles in the presence of various activating factors, and NLRP3 inflammasome has been most characterized. The maturation of inflammatory easpases and eytokines IL-1β and IL-18 in pyroptosis relies on the activation of inflammasomes. The final execution of pyroptosis relies on a new discovered protein, GSDMD, which forms pores on the cell membranes, and in turn leads cell swelling and lysis. As releasing intracellular inflammatory cytokines, pyroptosis exacerbates the inflammation.