The neurotrophin receptor p75NTR: novel functions and implications for diseases of the nervous system

Neurotrophins have long been known to promote the survival and differentiation of vertebrate neurons. However, these growth factors can also induce cell death through the p75 neurotrophin receptor (p75NTR), a member of the tumor necrosis factor receptor superfamily. Consistent with a function in controlling the survival and process formation of neurons, p75NTR is mainly expressed during early neuronal development. In the adult, p75NTR is re-expressed in various pathological conditions, including epilepsy, axotomy and neurodegeneration. Potentially toxic peptides, including the amyloid β- (Aβ-) peptide that accumulates in Alzheimer's disease, are ligands for p75NTR. Recent work also implicates p75NTR in the regulation of both synaptic transmission and axonal elongation. It associates with the Nogo receptor, a binding protein for axonal growth inhibitors, and appears to be the transducing subunit of this receptor complex.