化学生物学调控Gasdermin 介导的细胞焦亡及其治疗潜力
Chemical Modulation of Gasdermin-Mediated Pyroptosis and Therapeutic Potential.
机构信息
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA; Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio 44106, USA.
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
出版信息
J Mol Biol. 2022 Feb 28;434(4):167183. doi: 10.1016/j.jmb.2021.167183. Epub 2021 Aug 3.
Abstract
Pyroptosis, a lytic form of programmed cell death, both stimulates effective immune responses and causes tissue damage. Gasdermin (GSDM) proteins are a family of pore-forming executors of pyroptosis. While the most-studied member, GSDMD, exerts critical functions in inflammasome biology, emerging evidence demonstrates potential broad relevance for GSDM-mediated pyroptosis across diverse pathologies. In this review, we describe GSDM biology, outline conditions where inflammasomes and GSDM-mediated pyroptosis represent rational therapeutic targets, and delineate strategies to manipulate these central immunologic processes for the treatment of human disease.
摘要
细胞焦亡是一种细胞程序性死亡的形式，它既能刺激有效的免疫反应，又能导致组织损伤。Gasdermin (GSDM) 蛋白是细胞焦亡的一类形成孔的效应执行者。虽然研究最多的成员 GSDMD 在炎症小体生物学中发挥着关键作用，但新出现的证据表明，GSDM 介导的细胞焦亡在多种病理情况下具有潜在的广泛相关性。在这篇综述中，我们描述了 GSDM 的生物学特性，概述了炎症小体和 GSDM 介导的细胞焦亡作为合理治疗靶点的条件，并阐述了操纵这些核心免疫过程以治疗人类疾病的策略。
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