{"title":"Mechanistic insights into gasdermin-mediated pyroptosis","authors":"Yang Bai, Youdong Pan, Xing Liu","doi":"10.1038/s41580-025-00837-0","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"16 1","pages":""},"PeriodicalIF":81.3000,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Molecular Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41580-025-00837-0","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
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.
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.