In vivo functions of p75(NTR): challenges and opportunities for an emerging therapeutic target

The p75 neurotrophin receptor (p75(NTR)) functions at the molecular nexus of cell death, survival, and differentiation. In addition to its contribution to neurodegenerative diseases and nervous system injuries, recent studies have revealed unanticipated roles of p75(NTR) in liver repair, fibrinolysis, lung fibrosis, muscle regeneration, and metabolism. Linking these various p75(NTR) functions more precisely to specific mechanisms marks p75(NTR) as an emerging candidate for therapeutic intervention in a wide range of disorders. Indeed, small molecule inhibitors of p75(NTR) binding to neurotrophins have shown efficacy in models of Alzheimer's disease (AD) and neurodegeneration. Here, we outline recent advances in understanding p75(NTR) pleiotropic functions in vivo, and propose an integrated view of p75(NTR) and its challenges and opportunities as a pharmacological target.