Fig. 9.

Probable effect of mistletoe against muscle decline. IGF1 binds to IGF1 receptor leading to activation of PI3K/AKT/mTOR pathway. Mistletoe leads to higher phosphotylation of AKT resulting in activation of P70S6K, upregulation of myoD and myogenin expression and myogenesis. Mistletoe decreases phosphorylation of PTEN which dephosphorylates PIP₃, increasing PIP₂ level and resulting in a decreased AKT activity. Furthermore, mistletoe decreases expression of REDD2 which inhibits mTOR pathway. Mistletoe increases phosphorylation of FoxO supporting the observation that mistletoe could induce the phosphorylation of AMPK, which is a repressor of FoxO. AKT also causes phosphorylation and nuclear exclusion of FoxO which is key molecule inducing muscle atrophy by stimulating Murf1 and Atrogin-1. Additionally, FoxO-dependent activation of muscle atrophy is inhibited by PGC-1α