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细胞焦亡在炎症性疾病和癌症中的机制与治疗调控。

Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer.

机构信息

Shandong Provincial Key Laboratory of Animal Resistant, School of Life Sciences, Shandong Normal University, Jinan 250014, China.

出版信息

Int J Mol Sci. 2020 Feb 20;21(4):1456. doi: 10.3390/ijms21041456.

Abstract

Programmed Cell Death (PCD) is considered to be a pathological form of cell death when mediated by an intracellular program and it balances cell death with survival of normal cells. Pyroptosis, a type of PCD, is induced by the inflammatory caspase cleavage of gasdermin D (GSDMD) and apoptotic caspase cleavage of gasdermin E (GSDME). This review aims to summarize the latest molecular mechanisms about pyroptosis mediated by pore-forming GSDMD and GSDME proteins that permeabilize plasma and mitochondrial membrane activating pyroptosis and apoptosis. We also discuss the potentiality of pyroptosis as a therapeutic target in human diseases. Blockade of pyroptosis by compounds can treat inflammatory disease and pyroptosis activation contributes to cancer therapy.

摘要

程序性细胞死亡(PCD)被认为是一种由细胞内程序介导的病理性细胞死亡形式,它平衡了细胞死亡和正常细胞的存活。细胞焦亡是一种 PCD 类型,由炎症性半胱天冬酶切割 Gasdermin D(GSDMD)和凋亡半胱天冬酶切割 Gasdermin E(GSDME)诱导。本综述旨在总结由形成孔的 GSDMD 和 GSDME 蛋白介导的细胞焦亡的最新分子机制,这些蛋白可使质膜和线粒体膜通透性增加,从而激活细胞焦亡和细胞凋亡。我们还讨论了细胞焦亡作为人类疾病治疗靶点的潜力。通过化合物抑制细胞焦亡可以治疗炎症性疾病,而细胞焦亡的激活有助于癌症治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e7/7073143/171128f887de/ijms-21-01456-g001.jpg

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