Department of Emergency Medicine, Lanzhou University Second Hospital, Lanzhou, China.
Department of Emergency Medicine, Lanzhou University Second Hospital, Lanzhou, China.
Int Immunopharmacol. 2024 Jun 30;135:112321. doi: 10.1016/j.intimp.2024.112321. Epub 2024 May 24.
Sepsis is a life-threatening multi-organ dysfunction syndrome caused by an abnormal host response to infection. Regulated cell death is essential for maintaining tissue homeostasis and eliminating damaged, infected, or aging cells in multicellular organisms. Gasdermin D, as a member of the gasdermin family, plays a crucial role in the formation of cytoplasmic membrane pores. Research has found that GSDMD plays important roles in various forms of regulated cell death such as pyroptosis, NETosis, and necroptosis. Therefore, through mediating regulated cell death, GSDMD regulates different stages of disease pathophysiology. This article mainly summarizes the concept of GSDMD, its role in regulated cell death, its involvement in organ damage associated with sepsis-related injuries mediated by regulated cell death via GSDMD activation and introduces potential drugs targeting GSDMD that may provide more effective treatment options for sepsis patients through drug modification.
脓毒症是一种危及生命的多器官功能障碍综合征,由宿主对感染的异常反应引起。程序性细胞死亡对于维持组织内稳态以及清除多细胞生物中受损、感染或衰老的细胞是至关重要的。Gasdermin D 作为 gasdermin 家族的一员,在细胞质膜孔的形成中发挥着关键作用。研究发现 GSDMD 在多种形式的程序性细胞死亡中发挥着重要作用,如细胞焦亡、NETosis 和坏死性凋亡。因此,GSDMD 通过调节程序性细胞死亡,调节不同阶段的疾病病理生理学。本文主要总结了 GSDMD 的概念、它在程序性细胞死亡中的作用、它在通过 GSDMD 激活介导的与脓毒症相关损伤相关的器官损伤中的作用,并介绍了可能针对 GSDMD 的潜在药物,通过药物修饰,为脓毒症患者提供更有效的治疗选择。