Stroke is a major cause of death and disability worldwide that triggers a variety of neuropathological conditions, leading to the initiation of several pro-inflammatory mediators and neuronal damage. Neuroinflammation has been considered the potential therapeutic target and contributes to the pathology of ischemia and reperfusion. Pyroptosis is an inflammatory form of programmed cell death that plays an important role in immune protection against stroke. Gasdermin D (GSDMD) is the final executor of pyroptosis upon cleavage by caspases-1/4/5/11, followed by canonical and noncanonical inflammasome activation, leading to a series of inflammatory responses. GSDMD N-terminal domain assembles plasma membrane as well as organelle membrane pores to induce cytolysis, thereby triggering cytokine release and inflammatory-related cell death. In our review, we concisely summarized and highlighted the potential role of GSDMD-regulated pyroptosis and the biological characteristic of GSDMD as a therapeutic target in ischemic stroke. A better understanding of the roles of GSDMD may provide a theoretical basis for the design of novel therapeutic interventions for the treatment of ischemic stroke.

中风是全球范围内导致死亡和残疾的主要原因，可引发多种神经病理学状况，导致多种促炎介质和神经元损伤的发生。神经炎症已被认为是潜在的治疗靶点，并有助于缺血和再灌注的病理学。细胞焦亡是程序性细胞死亡的一种炎症形式，在针对中风的免疫保护中起着重要作用。Gasdermin D (GSDMD) 是被 caspase-1/4/5/11 裂解后细胞焦亡的最终执行者，随后是典型和非典型炎症小体激活，导致一系列炎症反应。GSDMD N 端结构域组装质膜以及细胞器膜孔以诱导细胞溶解，从而引发细胞因子释放和炎症相关的细胞死亡。在我们的评论中，我们简要总结并强调了 GSDMD 调节的细胞焦亡的潜在作用以及 GSDMD 作为缺血性卒中治疗靶点的生物学特性。更好地理解 GSDMD 的作用可能为设计用于治疗缺血性中风的新型治疗干预措施提供理论基础。