Huntingtin Ubiquitination Mechanisms and Novel Possible Therapies to Decrease the Toxic Effects of Mutated Huntingtin.

ABSTRACT: Huntington Disease (HD) is a dominant, lethal neurodegenerative disorder caused by the abnormal expansion (>35 copies) of a CAG triplet located in exon 1 of the HTT gene encoding the huntingtin protein (Htt). Mutated Htt (mHtt) easily aggregates, thereby inducing ER stress that in turn leads to neuronal injury and apoptosis. Therefore, both the inhibition of mHtt aggregate formation and the acceleration of mHtt degradation represent attractive strategies to delay HD progression, and even for HD treatment. Here, we describe the mechanism underlying mHtt degradation by the ubiquitin-proteasome system (UPS), which has been shown to play a more important role than the autophagy-lysosomal pathway. In particular, we focus on E3 ligase proteins involved in the UPS and detail their structure-funct

SUBMITTER: Fiorillo A 

PROVIDER: S-EPMC8709430 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature