p75^NTR known as a cell surface receptor for NGF, BDNF, NT-3 and NT-4, is also a receptor for b-amyloid, and for the myelin axon repellant protein MAG.^1,2,4,6 Binding of neurotrophins induces receptor dimerization followed by phosphorylation of receptor kinase residues and recruitment of intracellular proteins involved in signal transduction.

p75^NTR functions alone, or in functional complexes with the neurotrophin receptors trkA, trkB and trkC. p75^NTR signals via interaction with different transducers such as TRAF6, IRAK, and RIP-2, activating NF-κB, JNK and p38, and inactivating rhoA.^1,3,6 

Receptor degradation is mediated by a metalloproteinase-dependent shedding of the extracellular domain. p75^NTR binds all neurotrophins with similar nM affinity, but binds pro-neurotrophins with greater affinity, and is more potently activated by pro-neurotrophins.⁵

Overexpression of the intracellular domain in developing neurons induces apoptosis. NGF-dependent association of NRIF with p75^NTR contributes to pro-apoptotic signaling.^7,8 

Beta-amyloid peptide binds p75^NTR and stimulates pro apoptotic signaling by p75^NTR, suggesting that the receptor may be relevant for Alzheimer's disease.⁹