Compelling evidence indicates that repair of damage to the central nervous system (CNS) is inhibited by the presence of protein factors within myelin that prevent axonal regrowth. Myelin growth inhibitors and their common receptor have been identified as targets in the treatment of spinal cord injury and stroke. We have determined the NMR structure of one of the myelin growth inhibitors, the neurite outgrowth inhibitor (Nogo). We studied the structure of this protein alone and in the presence of dodecylphosphocholine micelles to mimic the natural cell membrane environment. Using computational docking methods, NMR data and mutagenesis results, we calculated the optimal protein-protein interface between our structure of Nogo and the Nogo receptor. We have developed a library of compounds that bind to Nogo in the nM concentration range and block function; these compounds promote axonal growth.

Blocking the neurite outgrowth inhibitor (Nogo) to promote neuroregeneration

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.