C9orf72-associated dipeptide protein repeats form A11-positive oligomers in amyotrophic lateral sclerosis and frontotemporal dementia.

ABSTRACT: Hexanucleotide repeat expansion in C9orf72 is one of the most common causes of amyotrophic lateral sclerosis and frontotemporal dementia. The hexanucleotide expansion, formed by GGGGCC (G4C2) repeats, leads to the production of five dipeptide protein repeats (DPRs) via repeat-associated non-AUG translation. Among the five dipeptide repeats, Gly-Arg, Pro-Arg, and Gly-Ala form neuronal inclusions that contain aggregates of the peptides. Several studies have attempted to model DPR-associated toxicity using various repeat lengths, which suggests a unique conformation that is cytotoxic and is independent of the repeat length. However, the structural characteristics of DPR aggregates have yet to be determined. Increasing evidence suggests that soluble species, such as oligomers, are the main cau

SUBMITTER: Bhatt N 

PROVIDER: S-EPMC10844744 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature