Targeted inhibition of the Shroom3-Rho kinase protein-protein interaction circumvents Nogo66 to promote axon outgrowth.

ABSTRACT:

Background

Inhibitory molecules in the adult central nervous system, including NogoA, impede neural repair by blocking axon outgrowth. The actin-myosin regulatory protein Shroom3 directly interacts with Rho kinase and conveys axon outgrowth inhibitory signals from Nogo66, a C-terminal inhibitory domain of NogoA. The purpose of this study was to identify small molecules that block the Shroom3-Rho kinase protein-protein interaction as a means to modulate NogoA signaling and, in the longer term, enhance axon outgrowth during neural repair.

Results

A high throughput screen for inhibitors of the Shroom3-Rho kinase protein-protein interaction identified CCG-17444 (Chem ID: 2816053). CCG-17444 inhibits the Shroom3-Rho kinase interaction in vitro with micromolar potency. This compou

SUBMITTER: Dickson HM 

PROVIDER: S-EPMC4467669 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature