Signaling pathways mediating anti-apoptotic action of neurotrophins.
Neurotrophins promote survival and suppress apoptosis in many populations of neurons. Currently, phosphatidylinositol-3 kinase (PI-3K) is recognized as the main mediator of this protective effect. However, most of the data collected so far on the anti-apoptotic signaling of neurotrophins were obtained using trophic withdrawal paradigms. Recent data from our and other groups indicate that extracellular-signal-regulated kinase 1/2 (Erk 1/2) may play a critical role in suppressing neuronal apoptosis triggered by cellular damage. Thus, it appears that either Erk1/2 or PI-3K, depending on the nature of the death-inducing stimulus, can mediate anti-apoptotic signaling of neurotrophins. In this review, we discuss the contribution of Erk1/2 and PI-3K to neuroprotection by neurotrophins. We also present data suggesting possible mechanisms by which these pathways might suppress neuronal death.
Hetman
M
M
Department of Environmental Health, University of Washington, Seattle, WA 98195-7234, USA. mhetman@u.washington.edu.
Xia
Z
Z
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases