Decoding the molecular mechanisms of pyroptosis and its therapeutic development prospects
TL;DR
This review systematically summarizes the molecular regulatory mechanisms of pyroptosis, encompassing classical and non-classical inflammasome pathways, activation and modulation of gasdermin proteins, and the intricate signaling networks involved.
Abstract
Pyroptosis is an emerging form of inflammatory programmed cell death primarily mediated by the gasdermin protein family, characterized by cell swelling, membrane pore formation, and the release of pro-inflammatory cytokines such as IL-1β and IL-18. This mode of cell death has garnered significant attention due to its critical involvement in a variety of diseases, including cancer, cardiovascular disorders, autoimmune diseases, and metabolic syndromes, positioning it as a promising therapeutic target. Despite advances, the complexity of pyroptosis regulation and its dual roles in disease pathogenesis present challenges that necessitate comprehensive understanding. This review systematically summarizes the molecular regulatory mechanisms of pyroptosis, encompassing classical and non-classical inflammasome pathways, activation and modulation of gasdermin proteins, and the intricate signaling networks involved. We further highlight the dualistic roles of pyroptosis in tumor development, immune modulation, and chronic inflammatory conditions. Incorporating the latest research progress, we explore emerging therapeutic strategies targeting pyroptosis, including small molecule inhibitors, nanomaterials, stem cell-derived exosomes, and gene regulation technologies, critically evaluating their clinical applicability and limitations. By providing an integrative overview of pyroptosis-related mechanisms and innovative treatment approaches, this article aims to offer a theoretical foundation and future research direction for precision medicine and novel drug development.