Neurotrophins function to regulate naturally occurring cell death of neurons during development. The prototype neurotrophin is nerve growth factor (NGF),
originally discovered in the 1950s as a soluble peptide promoting the survival of, and neurite outgrowth from, sympathetic ganglia. Three additional structurally homologous neurotrophic factors have been identified. These include brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) (also designated NT-5). These various neurotrophins stimulate the in vitro survival of distinct, but partially overlapping, populations of neurons. The cell surface receptors through which neurotrophins mediate their activity have been identified. For instance, the Trk A receptor is the preferential receptor for NGF, but also binds NT-3 and NT-4. The Trk B receptor binds both BDNF and NT-4 equally well, and binds NT-3 to a lesser extent, while the Trk C receptor only binds NT-3.