Neurotrophin signalling pathways regulating neuronal apoptosis

Recent evidence indicates that naturally occurring neuronal death in mammal s is regulated by the interplay between receptor-mediated prosurvival and p roapoptotic signals. The neurotrophins, a family of growth factors best kno wn for their positive effects on neuronal biology, have now been shown to m ediate both positive and negative survival signals, by signalling through t he Trk and p75 neurotrophin receptors, respectively. The mechanisms whereby these two neurotrophin receptors interact to determine neuronal survival h ave been difficult to decipher, largely because both can signal independent ly or coincidentally, depending upon the cell or developmental context. Non etheless, the past several years have seen significant advances in our unde rstanding of this receptor signalling system. In this review, we focus on t he proapoptotic actions of the p75 neurotrophin receptor (p75(NTR)), and on the interplay between Trk and p75(NTR) that determines neuronal survival.