Advances in the research of gasdermin-dependent pyroptosis mechanisms and therapeutic targets in inflammatory diseases

Inflammation, especially invasive bacterial inflammation, has always been a hot topic in medical research. With the emergence of superbugs and highly virulent viruses, current treatment methods are gradually revealing areas of deficiency. As an inflammatory form of cell death, the concept of pyroptosis offers new possibilities for the treatment of inflammation. Pyroptosis is typically triggered by inflammasomes and executed by the Gasdermin (GSDM) family. It is characterized by membrane perforation, cell swelling, and the release of cellular contents such as pro-inflammatory factors. Pyroptosis plays a crucial role in host immune defense, inflammatory diseases, and tumor regulation. In this review, we comprehensively explored each member of the GSDM family and its activation pathways, reviewed the cellular consequences of GSDM activation, and the role of GSDM-mediated pyroptosis in inflammatory diseases such as sepsis. We also provided a detailed account of the latest advancements in inflammation control targeting GSDM, aiming to offer new perspectives for precise therapies targeting pyroptosis.