The p75 neurotrophin receptor in human development and disease

The functional effects of nerve growth factor (NGF) and its precursor, pro-NGF, are thought to be mediated through binding of these ligands to one or both of their receptors, TrkA and p75NTR. While the signaling pathways and downstream effects of NGF binding to TrkA are reasonably well known, those related to the binding of NGF and pro-NGF to p75NTR are less well understood. Furthermore, p75NTR appears to play functional roles that are unrelated to its ability to bind NGF and pro-NGF, some of which are ligand-independent and others of which are dependent upon binding to other neurotrophins. As these functional roles and their biochemical mechanisms become better known, the importance of p75NTR, related receptors, and both extracellular ligands and intracellular interactors and effectors for human development and health has become increasingly apparent. A complete understanding of p75NTR and its cellular partners is best served by approaching the remaining questions from both sides, with studies of function in normal states and studies of dysfunction in aberrant states mutually informing one another.