A novel inhibitor of p75-neurotrophin receptor improves functional outcomes in two models of traumatic brain injury.

ABSTRACT: The p75 neurotrophin receptor is important in multiple physiological actions including neuronal survival and neurite outgrowth during development, and after central nervous system injury. We have discovered a novel piperazine-derived compound, EVT901, which interferes with p75 neurotrophin receptor oligomerization through direct interaction with the first cysteine-rich domain of the extracellular region. Using ligand binding assays with cysteine-rich domains-fused p75 neurotrophin receptor, we confirmed that EVT901 interferes with oligomerization of full-length p75 neurotrophin receptor in a dose-dependent manner. Here we report that EVT901 reduces binding of pro-nerve growth factor to p75 neurotrophin receptor, blocks pro-nerve growth factor induced apoptosis in cells expressing p75 neuro

SUBMITTER: Delbary-Gossart S 

PROVIDER: S-EPMC4892754 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature