Repeat length of C9orf72-associated glycine-alanine polypeptides affects their toxicity.

ABSTRACT: G₄C₂ hexanucleotide repeat expansions in a non-coding region of the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). G₄C₂ insertion length is variable, and patients can carry up to several thousand repeats. Dipeptide repeat proteins (DPRs) translated from G₄C₂ transcripts are thought to be a main driver of toxicity. Experiments in model organisms with relatively short DPRs have shown that arginine-rich DPRs are most toxic, while polyGlycine-Alanine (GA) DPRs cause only mild toxicity. However, GA is the most abundant DPR in patient brains, and experimental work in animals has generally relied on the use of low numbers of repeats, with DPRs often tagged f

SUBMITTER: Moron-Oset J 

PROVIDER: S-EPMC10463776 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature