p75 neurotrophin receptor signaling in nervous system injury and degeneration: paradox and opportunity

Injury or insult to the adult nervous system often results in reactivation of signaling pathways that are normally only active during development. The p75 neurotrophin receptor (p75(NTR)) is one such signaling molecule whose expression increases markedly following neural injury in many of the same cell types that express p75(NTR) during development. A series of studies during the past decade has demonstrated that p75(NTR) signaling contributes to neuronal and glial cell damage, axonal degeneration and dysfunction during injury and cellular stress. Why the nervous system reacts to injury by inducing a molecule that aids the demise of cells and axons is a biological paradox that remains to be explained satisfactorily. On the other hand, it may offer unique therapeutic opportunities for limiting the severity of nervous system injury and disease.