Impact of differential and time-dependent autophagy activation on therapeutic efficacy in a model of Huntington disease.

ABSTRACT: Activation of macroautophagy/autophagy, a key mechanism involved in the degradation and removal of aggregated proteins, can successfully reverse Huntington disease phenotypes in various model systems. How neuronal autophagy impairments need to be considered in Huntington disease progression to achieve a therapeutic effect is currently not known. In this study, we used a mouse model of HTT (huntingtin) protein aggregation to investigate how different methods and timing of autophagy activation influence the efficacy of autophagy-activating treatment in vivo. We found that overexpression of human TFEB, a master regulator of autophagy, did not decrease mutant HTT aggregation. On the other hand, Becn1 overexpression, an autophagic regulator that plays a key role in autophag

SUBMITTER: Brattas PL 

PROVIDER: S-EPMC8204969 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature