Pyroptosis in health and disease:mechanisms,regulation and clinical perspective

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外文摘要：Pyroptosis is a type of programmed cell death characterized by cell swelling and osmotic lysis,resulting in cytomembrane rupture and release of immunostimulatory components,which play a role in several pathological processes.Significant cellular responses to various stimuli involve the formation of inflammasomes,maturation of inflammatory caspases,and caspase-mediated cleavage of gasdermin.The function of pyroptosis in disease is complex but not a simple angelic or demonic role.While inflammatory diseases such as sepsis are associated with uncontrollable pyroptosis,the potent immune response induced by pyroptosis can be exploited as a therapeutic target for anti-tumor therapy.Thus,a comprehensive review of the role of pyroptosis in disease is crucial for further research and clinical translation from bench to bedside.In this review,we summarize the recent advancements in understanding the role of pyroptosis in disease,covering the related development history,molecular mechanisms including canonical,non-canonical,caspase 3/8,and granzyme-mediated pathways,and its regulatory function in health and multiple diseases.Moreover,this review also provides updates on promising therapeutic strategies by applying novel small molecule inhibitors and traditional medicines to regulate pyroptosis.The present dilemmas and future directions in the landscape of pyroptosis are also discussed from a clinical perspective,providing clues for scientists to develop novel drugs targeting pyroptosis.

作者：

Yifan Liu、Renjie Pan、Yuzhen Ouyang、Wangning Gu、Tengfei Xiao、Hongmin Yang、Ling Tang、Hui Wang、Bo Xiang、Pan Chen

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作者单位：

The Affiliated Cancer Hospital of Xiangya School of Medicine,Central South University/Hunan Cancer Hospital,Changsha 410013,China

Department of Oncology,Xiangya Hospital,Central South University,87th Xiangya road,Changsha 410008 Hunan province,China

Department of Neurology,Xiangya Hospital,Central South University,87th Xiangya road,Changsha 410008 Hunan province,China

基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaKey Research and Development Program of Hunan ProvinceKey Research and Development Program of Hunan ProvinceKey Research and Development Program of Hunan ProvinceKey Research and Development Program of Hunan ProvinceScientific Research Program of FuRong LaboratoryScientific Research Program of FuRong LaboratoryNatural Science Foundation of Hunan ProvinceNatural Science Foundation of Hunan ProvinceNatural Science Foundation of Hunan ProvinceNatural Science Foundation of Hunan ProvinceHunan Cancer Hospital Climb PlanHunan Cancer Hospital Climb PlanHunan Cancer Hospital Climb Plan

项目编号：

8217320182272758U23A204562022SK20262023DK20012024DK2007China2023SK2094China2022JJ700202023JJ601202024JJ3036China2023NSFC-B005ZX2021003China

出版年：

2024

DOI：

10.1038/s41392-024-01958-2

信号转导与靶向治疗(英文)

CSTPCD

ISSN：

年,卷(期)：2024.9(10)