Antiapoptotic and pronecrotic actions of neurotrophins.

Neurotrophins promote the differentiation, growth, and survival of neurons in the nervous system. Specifically, neurotrophins promote neuronal survival by interfering with programmed cell death or apoptosis. In addition to roles of neurotrophins as survival factors, neurotrophins can act as risk factors of neuronal injury under various pathological conditions. Neurotrophins markedly potentiate neuronal cell necrosis induced by activation of N-methyl-D-aspartate receptors, deprivation of oxygen and glucose, and free radicals. Moreover, prolonged exposure to neurotrophins results in widespread neuronal necrosis through free radical-mediated mechanisms. Whereas cellular and molecular mechanisms underlying antiapoptosis action of neurotrophins have been well documented, extensive study will be needed to delineate mechanisms for the neurotrophin-induced neuronal necrosis through activation of Trk tyrosine kinase receptors.