C9orf72 suppresses systemic and neural inflammation induced by gut bacteria.

ABSTRACT: A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia^1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration^3-9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins⁵ before its non-canonical translation into neural-toxic dipeptide proteins^3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation^6-9. Notably, the effects of the repeat expan

SUBMITTER: Burberry A 

PROVIDER: S-EPMC7416879 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature