Role of neurotrophins in preventing glutamate induced neuronal cell death.

Neurotrophic factors are important regulators of neuronal survival and differentiation during embryonic development. However, these molecules also act on fully mature neurons and have been shown to rescue cells following brain damage and in degenerating diseases. The neurotrophins comprise a family of related molecules including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF, neurotrophin-3 (NT-3) and neurotrophin 4/5 (NT 4/5). They are all expressed in the peripheral but particularly also in some parts of the central nervous system. Moreover, NGF and BDNF mRNAs are induced by neuronal activity mainly through glutamate receptor activation. The functional significance, however, of the enhanced neuronal production of neurotrophins and other growth factors following stimulation by glutamate is largely unknown. Glutamate in large doses or after prolonged receptor activation causes neuronal death as observed in different neuropathological states. Here, evidence is presented supporting the view that neurotrophic factors such as BDNF and fibroblast growth factors (FGF) promote central neuronal survival after excessive glutamate exposures.