Modulation of miRNA networks by exercise in muscular dystrophies: therapeutic insights and future directions.

Muscular dystrophies (MDs) encompass a diverse group of hereditary disorders characterized by progressive skeletal muscle degeneration and weakness. While current therapeutic strategies primarily focus on symptom management, physical exercise is increasingly recognized as a potent intervention to attenuate disease progression and preserve muscle function. Recent evidence highlights the critical role of microRNAs (miRNAs)—small non-coding RNAs—in post-transcriptional gene regulation, particularly within muscle biology. Exercise dynamically modulates the expression of specific myomiRs (e.g., miR-1, miR-133, miR-206) and inflammation-associated miRNAs (miR-29, miR-146a), which collectively govern processes such as fibrosis, oxidative stress, and regeneration. This review synthesizes current knowledge on the exercise-mediated regulation of miRNA networks in MDs. We delineate the molecular mechanisms linking physical activity to miRNA biogenesis and examine the downstream therapeutic effects on dystrophic pathology. Furthermore, we critically assess the gap between preclinical success in animal models and the scarcity of human clinical data, proposing a roadmap for developing precision exercise interventions that target miRNA networks to enhance therapeutic outcomes. Precision in this context entails miRNA-guided exercise dosing (e.g., adjusting intensity based on real-time miRNA expression profiles), biomarker-driven personalization (e.g., using circulating miRNAs to tailor regimens for individual patients), and integration with gene or exon-skipping therapies to synergistically address subtype-specific pathologies in MDs such as DMD, BMD, and LGMD.