Neuroprotective role of neurotrophins: relationship between nerve growth factor and apoptotic cell survival pathway after cerebral ischemia.

Neurotrophins provide a neuroprotective effect in a variety of brain diseases. Recent reports demonstrate that neurotrophins play an important role in the regulation of apoptotic neuronal cell death and in the relationship between this machinery and activation of cell survival pathways. The cascade reactions of the two major cell survival pathways, mitogen-activated protein kinase and phosphatidylinositol 3-kinase, are known to play a critical role in the regulation of apoptotic neuronal cell survival pathways. Neurotrophins such as nerve growth factor regulate these two cell survival pathways in in vitro studies. However, the role of neurotrophins in cell survival remains unclear in in vivo apoptotic neuronal cell death. We discuss the mechanism of neuroprotection by neurotrophins and also discuss cell survival effect of nerve growth factor on apoptotic neuronal cell death after in vivo cerebral ischemia.