ULK overexpression mitigates motor deficits and neuropathology in mouse models of Machado-Joseph disease.

ABSTRACT: Machado-Joseph disease (MJD) is a fatal neurodegenerative disorder clinically characterized by prominent ataxia. It is caused by an expansion of a CAG trinucleotide in ATXN3, translating into an expanded polyglutamine (polyQ) tract in the ATXN3 protein, that becomes prone to misfolding and aggregation. The pathogenesis of the disease has been associated with the dysfunction of several cellular mechanisms, including autophagy and transcription regulation. In this study, we investigated the transcriptional modifications of the autophagy pathway in models of MJD and assessed whether modulating the levels of the affected autophagy-associated transcripts (AATs) would alleviate MJD-associated pathology. Our results show that autophagy is impaired at the transcriptional level in MJD, affecting mu

SUBMITTER: Vasconcelos-Ferreira A 

PROVIDER: S-EPMC8753369 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature