Resveratrol protects neuronal-like cells expressing mutant Huntingtin from dopamine toxicity by rescuing ATG4-mediated autophagosome formation

In this study, we found that Dopamine affects the stability and function of ATG4, a redox-sensitive cysteine-protein involved in the processing of LC3, a key step in the formation of autophagosomes. Resveratrol, a dietary polyphenol with anti-oxidant and pro-autophagic properties, has shown neuroprotective potential in HD. Yet the molecular mechanism through which Resveratrol can protect HD cells against DA is not known. Here, we show that Resveratrol prevents the generation of ROS, restores the level of ATG4, allows the lipidation of LC3, facilitates the degradation of polyQ-Htt aggregates and protects the cells from Dopamine toxicity.The present findings provide a mechanistic explanation of the neuroprotective activity of Resveratrol and support its inclusion in a therapeutic regimen to slow down HD progression.
Source: Neurochemistry International - Category: Neuroscience Source Type: research