Neurotrophic Factor Protection against Excitotoxic Neuronal Death

Abstract

Neurotrophic factors are polypeptides capable of promoting neuronal survival in both the developing and the adult brain. In addition to the neurotrophins, NGF, brain-derived neurotropic factor, and NT-3 to -6, other neurotrophic factors include ciliary neurotrophic factor, fibroblast growth factors, insulin-like growth factors, members of the transforming growth factor superfamily, members of the epidermal growth factor family, and other cytokines such as leukemia inhibitory factor, oncostatin M, and interleukins-6 and -11. One condition under which these factors promote survival is the challenge of neurons with analogs of excitatory amino acid transmitters. Such analogs, including quinolinic acid, kainic acid, and ibotenic acid, are frequently employed as models of neurological diseases such as Huntington's disease, Parkinson's disease, Alzheimer's disease, epilepsy, cerebellar degenerations, and amyotrophic lateral sclerosis. Excitotoxicity also plays a role in neu ronal death caused by focal ischemia, hypoglycemia, or trauma. Although much has been learned about the mechanisms of both the action of neurotrophic factors and of cell death in response to excitotoxins, the mechanism of protection by these factors remains uncertain. This review explores the biochemical and phys iological changes mediated by neurotrophic factors that may underlie their ability to protect against excito toxic cell death. Second messenger pathways used degenerately by both excitotoxins and neurotrophic factors are discussed as a potential site of interaction mediating the protective effects of neurotrophic factors. Particular attention is also paid to the importance of the route of neurotrophic factor delivery in conferring neuroprotection in particular excitotoxic models. The Neuroscientist 1:286-297, 1995