Targeting pyroptosis for skeletal muscle atrophy: mechanistic insights and therapeutic perspectives

Abstract

Skeletal muscle atrophy is a progressive syndrome characterised by the loss of skeletal muscle mass and function. It significantly impairs patients’ quality of life and clinical prognosis. Current intervention strategies have limited efficacy, necessitating the identification of novel therapeutic targets. Pyroptosis, a form of programmed cell death mediated by the Gasdermin protein family and accompanied by intense inflammatory responses, has been found to play a pivotal role in skeletal muscle homeostasis. Through core signalling axes NLRP3-caspase-1-GSDMD, it triggers the release of large amounts of inflammatory cytokines, establishing and sustaining a chronic inflammatory microenvironment that drives protein degradation. This review systematically elucidates the core molecular mechanisms of pyroptosis, revealing its role in exacerbating skeletal muscle atrophy through direct damage to myofibres and the establishment of chronic inflammatory microenvironments. It summarises potential intervention strategies targeting pyroptosis, further analysing key challenges in current research and prospects for clinical translation.