Figure 1.

The relationship between PI3-K–Akt–mTOR signaling and autophagy in muscular dystrophy. The major anabolic pathway regulating protein synthesis in skeletal muscle is mTOR/TORC1 signaling. Upstream trigger (IGF-1, mechanical stress, etc.) activates mTOR signaling through a number of different intermediary proteins such as Akt and Rheb. Several anabolic stimulation increases the amount of activated Akt, which blocks the nuclear translocation of Foxo3 to enhance the expression of autophagy-related genes (Bnip, LC3, and Atg12) and atrogene (atrogin-1 and MuRF-1). In dystrophic muscle, higher Akt potently blocks the inhibition of Rheb by TSC-1/TSC-2, and hyperactivate mTORC1. Unnecessary activated mTORC1 would extremely enhance protein synthesis and blocks autophagy-dependent signaling. Therefore, muscular dystrophy exhibits apparent defect of autophagic process similar to sarcopenic muscle.