TFEB, FOXO3 and TLR4 in resveratrol-induced autophagy in a mucopolysaccharidosis IIIB mouse model

Mucopolysaccharidosis (MPS) type IIIB is the progressive degeneration of the central nervous system. Resveratrol is proposed as a potential therapeutic molecule as a drug reducing inflammation and for improving behavior of MPS mice. Here we investigated autophagy in correlation with immune response in an MPS IIIB mouse model. The effects of resveratrol on mouse behavior and the levels of selected cytokines that influence the inflammation were assessed. The study was performed on both male and female mice treated or not with resveratrol. The results of behavioral, molecular and biochemical experiments confirmed that autophagy and immune response are disturbed in MPS IIIB mice. A correlation between behavioral disturbances and levels of heparan sulfate and TLR4 could be observed. The FOXO3 transcription factor was identified as one of the key factors in the resveratrol-mediated stimulation of the autophagy process in the MPS IIIB mouse model, though it was not the sole pathway induced by this compound. We conclude that resveratrol can modulate the degradation of glycosaminoglycans and also may contribute to the reduction of inflammation and the normalization of animal behavior in the MPS IIIB model.