G-quadruplex-binding small molecules ameliorate <i>C9orf72</i> FTD/ALS pathology <i>in vitro</i> and <i>in vivo</i>.

ABSTRACT: Intronic GGGGCC repeat expansions in C9orf72 are the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which are characterised by degeneration of cortical and motor neurons, respectively. Repeat expansions have been proposed to cause disease by both the repeat RNA forming foci that sequester RNA-binding proteins and through toxic dipeptide repeat proteins generated by repeat-associated non-ATG translation. GGGGCC repeat RNA folds into a G-quadruplex secondary structure, and we investigated whether targeting this structure is a potential therapeutic strategy. We performed a screen that identified three structurally related small molecules that specifically stabilise GGGGCC repeat G-quadruplex RNA We investigated their effect in C9orf

SUBMITTER: Simone R 

PROVIDER: S-EPMC5760849 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature