Mechanistic insights into gasdermin-mediated pyroptosis

IF 81.3 1区 生物学 Q1 CELL BIOLOGY
Yang Bai, Youdong Pan, Xing Liu
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引用次数: 0

Abstract

Pyroptosis, a novel mode of inflammatory cell death, is executed by membrane pore-forming gasdermin (GSDM) family members in response to extracellular or intracellular injury cues and is characterized by a ballooning cell morphology, plasma membrane rupture and the release of inflammatory mediators such as interleukin-1β (IL-1β), IL-18 and high mobility group protein B1 (HMGB1). It is a key effector mechanism for host immune defence and surveillance against invading pathogens and aberrant cancerous cells, and contributes to the onset and pathogenesis of inflammatory and autoimmune diseases. Manipulating the pore-forming activity of GSDMs and pyroptosis could lead to novel therapeutic strategies. In this Review, we discuss the current knowledge regarding how GSDM-mediated pyroptosis is initiated, executed and regulated, its roles in physiological and pathological processes, and the crosstalk between different modes of programmed cell death. We also highlight the development of drugs that target pyroptotic pathways for disease treatment.

Abstract Image

气凝胶介导的焦亡机制
焦亡是炎症细胞死亡的一种新模式,是由膜成孔气皮蛋白(GSDM)家族成员对细胞外或细胞内损伤的反应而导致的,其特征是细胞形态呈气球状,质膜破裂,炎症介质如白细胞介素-1β (IL-1β)、IL-18和高迁移率组蛋白B1 (HMGB1)的释放。它是宿主免疫防御和监视入侵病原体和异常癌细胞的关键效应机制,并参与炎症和自身免疫性疾病的发生和发病机制。操纵GSDMs的成孔活性和焦亡可能导致新的治疗策略。在这篇综述中,我们讨论了目前关于gsdm介导的焦亡是如何启动、执行和调节的,它在生理和病理过程中的作用,以及不同模式的程序性细胞死亡之间的串扰。我们还强调了针对疾病治疗的焦亡途径的药物开发。
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来源期刊
Nature Reviews Molecular Cell Biology
Nature Reviews Molecular Cell Biology 生物-细胞生物学
CiteScore
173.60
自引率
0.50%
发文量
118
审稿时长
6-12 weeks
期刊介绍: Nature Reviews Molecular Cell Biology is a prestigious journal that aims to be the primary source of reviews and commentaries for the scientific communities it serves. The journal strives to publish articles that are authoritative, accessible, and enriched with easily understandable figures, tables, and other display items. The goal is to provide an unparalleled service to authors, referees, and readers, and the journal works diligently to maximize the usefulness and impact of each article. Nature Reviews Molecular Cell Biology publishes a variety of article types, including Reviews, Perspectives, Comments, and Research Highlights, all of which are relevant to molecular and cell biologists. The journal's broad scope ensures that the articles it publishes reach the widest possible audience.
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