C9orf72 regulates the unfolded protein response and stress granule formation by interacting with eIF2α.

ABSTRACT: Rationale: A C9orf72 hexanucleotide repeat expansion (GGGGCC) is the most common genetic origin of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Haploinsufficiency of C9orf72 has been proposed as a possible disease mechanism (loss-of-function mechanism). Additionally, the aberrantly activated unfolded protein response (UPR) and stress granule (SG) formation are associated with the etiopathology of both ALS and FTD. However, the molecular determinants in this pathogenesis are not well characterized. Methods: We performed an immunoprecipitation-mass spectrometry (IP-MS) assay to identify potential proteins interacting with the human C9orf72 protein. We used C9orf72 knockout cell and rat models to determine the roles of C9orf72 in translati

SUBMITTER: Zheng W 

PROVIDER: S-EPMC9691347 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature