Correction of GSK3β at young age prevents muscle pathology in mice with myotonic dystrophy type 1.

ABSTRACT: Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disease caused by expanded CUG repeats, which misregulate RNA metabolism through several RNA-binding proteins, including CUG-binding protein/CUGBP1 elav-like factor 1 (CUGBP1/CELF1) and muscleblind 1 protein. Mutant CUG repeats elevate CUGBP1 and alter CUGBP1 activity via a glycogen synthase kinase 3β (GSK3β)-cyclin D3-cyclin D-dependent kinase 4 (CDK4) signaling pathway. Inhibition of GSK3β corrects abnormal activity of CUGBP1 in DM1 mice [human skeletal actin mRNA, containing long repeats ( HSA^LR) model]. Here, we show that the inhibition of GSK3β in young HSA^LR mice prevents development of DM1 muscle pathology. Skeletal muscle in 1-yr-old HSA^LR mice, treated at 1.5 mo for 6 wk with the inhibi

SUBMITTER: Wei C 

PROVIDER: S-EPMC5893173 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature