Advances in gasdermin activation, regulation, and targeted drug development

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d4048752e107">Proteins of the gasdermin family are executors of pyroptosis. Upon cleavage-dependent/independent activation, gasdermins form pores on the cell membrane, which damage the integrity of the cell membrane and lead to pro-inflammatory cellular content release and lytic cell death. The role of gasdermin in pyroptosis-associated diseases, such as allergic diseases, neurologic disorders, infections, and cancer, showcases the tremendous therapeutic potential of targeting gasdermin. New insights into non-pyroptotic functions continue to further our understanding of gasdermin. Herein we review current knowledge of the gasdermin family, demonstrating the mechanism of activation, downstream effects, and regulatory mechanisms. We also discuss the association with pyroptosis-associated diseases and the functions beyond pyroptosis, shedding light on the broader roles in various pathologic processes. Furthermore, we summarize the advances in the development of targeted agonists and inhibitors with strategies for developing pyroptosis-based anti-tumor therapies. </p>

Frontiers | Roles of pyroptosis and immune infiltration in aortic dissection

Introduction: Aortic dissection (AD) is often fatal, and its pathogenesis involves immune infiltration and pyroptosis, though the molecular pathways connecti...

JCI - NLRP3 inflammasome induces CD4+ T cell loss in chronically HIV-1–infected patients

An ancient defense mechanism: Conservation of gasdermin-mediated pyroptosis

Gasdermin (GSDM) is a family of pore-forming proteins involved in various cellular processes such as cell death and inflammation. This Primer explores a PLOS Biology study of the evolutionary history of GSDMs across metazoan species, including Amphioxus, highlighting the conservation and divergence of GSDME in inducing pyroptosis in response to infection.

An ancient defense mechanism: Conservation of gasdermin-mediated pyroptosis

Gasdermin (GSDM) is a family of pore-forming proteins involved in various cellular processes such as cell death and inflammation. This Primer explores a PLOS Biology study of the evolutionary history of GSDMs across metazoan species, including Amphioxus, highlighting the conservation and divergence of GSDME in inducing pyroptosis in response to infection.

An ancient defense mechanism: Conservation of gasdermin-mediated pyroptosis

Gasdermin (GSDM) is a family of pore-forming proteins involved in various cellular processes such as cell death and inflammation. This Primer explores a PLOS Biology study of the evolutionary history of GSDMs across metazoan species, including Amphioxus, highlighting the conservation and divergence of GSDME in inducing pyroptosis in response to infection.

Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis

Characterization of Gasdermin E-mediated pyroptosis in the basal chordate amphioxus reveals that it is transcriptionally regulated by IRF1/8, involved in bacteria induced tissue damage, and inhibited by caspase inhibitor.