Fig. 6. Consequences of HDAC6 activity inhibition regulation through TubA treatment in DMD mice model.

HDAC6 inhibitor such as TubA induces a decrease in HDAC6 activity that leads to an acetylation of α-tubulin and of Smad3. HDAC6 pharmacological inhibition allows an increase of α-tubulin acetylation to restore DGC and stabilize MT network/NMJ organization. Additionally, specific inhibition of HDAC6 increases acetylation of Smad3 which can interfere with TGF-β signaling to both reduce muscle atrophy by reducing the expression of key actors such as MAFbx/MuRF1 and to stimulate protein synthesis via mTOR pathway. Our results identify HDAC6 as a pharmacological target of interest for DMD.