Pyroptosis is a novel inflammatory form of programmed cell death that is distinct from apoptosis, ferroptosis, necroptosis and autophagy. Its core feature is the formation of plasma membrane pores mediated by the Gasdermin family of proteins, which leads to cell membrane rupture and the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), thereby triggering a robust inflammatory response. Pyroptosis can participate in the pathogenesis of various skeletal muscle diseases, including skeletal muscle atrophy, idiopathic inflammatory myopathies (IIM), and rhabdomyolysis (RM), through molecular pathways including Caspase-1-dependent canonical pathway, Caspase-4/5/11-dependent non-classical pathway, Caspase-3/8-mediated pathways, and granzyme-mediated pathways. Exercise intervention, as a safe and effective non-pharmacological therapy, has shown significant potential in the prevention and treatment of skeletal muscle diseases. Its beneficial effects are closely related to the regulation of pyroptosis signaling pathways. Both aerobic exercise and resistance training can downregulate the expression of key pyroptosis molecules, thereby inhibiting inflammasome activation and the release of pro-inflammatory factors, ultimately alleviating muscle damage and inflammatory responses. However, different forms of exercise exhibit differential effects on the regulation of pyroptosis, and specific exercise prescriptions need to be personalized based on age, disease type, and severity. However, the specific molecular targets through which exercise mediates pyroptosis in the regulation of skeletal muscle diseases have not been fully elucidated, and the differential effects of various exercise modalities on specific pyroptotic pathways still require systematic investigation. This article reviews the developmental trajectory of pyroptosis, systematically summarizes the molecular mechanisms of pyroptosis and its roles in major skeletal muscle diseases, and outlines the regulatory effects of different forms of exercise on pyroptosis. The aim is to clarify the mechanisms linking exercise and pyroptosis, providing a comprehensive theoretical reference for the development of strategies targeting pyroptosis in the prevention and treatment of skeletal muscle diseases, while also offering a scientific basis for designing personalized exercise intervention programs in clinical practice.
LI et al. (Thu,) studied this question.