The contribution of proteasomal impairment to autophagy activation by C9orf72 poly-GA aggregates.

ABSTRACT:

Background

Poly-GA, a dipeptide repeat protein unconventionally translated from GGGGCC (G4C2) repeat expansions in C9orf72, is abundant in C9orf72-related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9orf72-ALS/FTD). Although the poly-GA aggregates have been identified in C9orf72-ALS/FTD neurons, the effects on UPS (ubiquitin-proteasome system) and autophagy and their exact molecular mechanisms have not been fully elucidated.

Results

Herein, our in vivo experiments indicate that the mice expressing ploy-GA with 150 repeats instead of 30 repeats exhibit significant aggregates in cells. Mice expressing 150 repeats ploy-GA shows behavioral deficits and activates autophagy in the brain. In vitro findings suggest that the poly-GA aggregates influence pr

SUBMITTER: Pu M 

PROVIDER: S-EPMC11803000 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature