Abstract:

Neurotrophins (NTs) are implicated in the maintenance and survival of the peripheral and central nervous systems and mediate several forms of synaptic plasticity. Members of the family include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT3, and NT4. NTs were first identified as survival factors for developing neurons, but are pleiotropic molecules that can exert a variety of functions, including the regulation of neuronal differentiation, axonal and dendritic growth, and synaptic plasticity. NTs interact with two distinct types of receptors: the common p75 neurotrophin receptor, which belongs to the tumor necrosis factor receptor superfamily of death receptors and the Trk receptor tyrosine kinase family. Trks contain an extracellular domain at which the NT binds, a single transmembrane domain, and an intracellular domain with tyrosine kinase activity. Three different Trks have been identified during the vertebrate evolution: TrkA, TrkB, and TrkC. NGF is the preferred ligand for TrkA, BDNF, and NT4/5 are preferred for TrkB, and NT3 for TrkC.