Targeting pyroptosis as a preventive and therapeutic approach for stroke

作者：Junpeng Long, Yang Sun, Shasha Liu, Songwei Yang, Chen Chen, Zhao Zhang, Shifeng Chu, Yantao Yang, Gang Pei, Meiyu Lin, Qian Yan, Jiao Yao, Yu-Ting Lin, Fan Yi, Lei Meng, Yong Tan, Qidi Ai, Nai‐Hong Chen · 发表于：Cell Death Discovery · 年份：2023 · DOI：10.1038/s41420-023-01440-y · 被引用次数：140 · 研究领域：Inflammasome and immune disorders、Gout, Hyperuricemia, Uric Acid、Streptococcal Infections and Treatments

Stroke has caused tremendous social stress worldwide, yet despite decades of research and development of new stroke drugs, most have failed and rt-PA (Recombinant tissue plasminogen activator) is still the accepted treatment for ischemic stroke. the complexity of the stroke mechanism has led to unsatisfactory efficacy of most drugs in clinical trials, indicating that there are still many gaps in our understanding of stroke. Pyroptosis is a programmed cell death (PCD) with inflammatory properties and are thought to be closely associated with stroke. Pyroptosis is regulated by the GSDMD of the gasdermin family, which when cleaved by Caspase-1/Caspase-11 into N-GSDMD with pore-forming activity can bind to the plasma membrane to form small 10-20 nm pores, which would allow the release of inflammatory factors IL-18 and IL-1β before cell rupture, greatly exacerbating the inflammatory response. The pyroptosis occurs mainly in the border zone of cerebral infarction, and glial cells, neuronal cells and brain microvascular endothelial cells (BMECs) all undergo pyroptosis after stroke, which largely exacerbates the breakdown of the blood-brain barrier (BBB) and thus aggravates brain injury. Therefore, pyroptosis may be a good direction for the treatment of stroke. In this review, we focus on the latest mechanisms of action of pyroptosis and the process by which pyroptosis regulates stroke development. We also suggest potential therapeutic stroke drugs that target the pyroptosis pathway,...