Overview

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle weakness due to the absence of dystrophin. This study investigates the disruption of autophagy, a cellular process responsible for degrading damaged proteins and organelles, in the skeletal muscles of DMD patients and mdx mice, a common model for DMD.

Key Findings

• Downregulation of Autophagy-Related Genes: Autophagy-related genes are significantly downregulated in dystrophin-deficient muscles.
• Phosphorylation of Key Transcription Factors: FoxO and TFEB are phosphorylated, preventing their nuclear entry and reducing autophagy-related gene expression.
• Impaired Autophagic Process: The failure in autophagosome-lysosome fusion leads to the accumulation of autophagosomes.

Potential Therapeutic Approaches

• SIRT1 Activation with Resveratrol: Resveratrol reduces the phosphorylation of FoxO and TFEB, restoring autophagic activity and improving muscle function in mdx mice.
• Transcriptional Regulation Strategies: Targeting transcriptional dysregulation of autophagy-related genes could be a promising approach for mitigating muscle degeneration in DMD.

Conclusion

This study highlights the importance of correcting the transcriptional suppression of autophagy-related genes in DMD to restore proper autophagic function. Future research should explore additional transcription factors and epigenetic mechanisms involved in this process to develop more effective treatments for DMD.