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Extracellular signal regulated kinases 1 and 2 (ERK1/2) regulate cellular responses to a varietyof extracellular stimuli. In the nervous system, ERK1/2 is critical for neur-onal differentiation, plasticityand mayalso modulate neuronal survival. In this minireview, we present evidence that supports prosurvival activityof ERK1/2 in neurons. Several reports suggest that ERK1/2 mediates neuropro-tective activityof extracellular factors, including neurotro-phins. In addition, ERK1/2 is activated byneuronal injury | Eur. J. Biochem. 271 2050-2055 2004 FEBS 2004 doi 10.1111 j.1432-1033.2004.04133.x MINIREVIEW Role of extracellular signal regulated kinases 1 and 2 in neuronal survival Michal Hetman1 2 3 and Agata Gozdz1 1 Kentucky Spinal Cord Research Injury Center and Departments of Neurological Surgery and 2Pharmacology and Toxicology University of Louisville KY USA 3Nencki Institute Warsaw Poland Extracellular signal regulated kinases 1 and 2 ERK1 2 regulate cellular responses to a variety of xxacicellukir stimuli. In the nervous system ERK1 2 is critical for neuronal differentiation plasticity add may olso modulate neuronal survival. In this minireview we present evidence that supports prosurvival activity ff ERKf 2 m neurons. Several reports suggest that ERK1 2 mediates neuropro-tective activityof extracellular factors including neurotro-phins. In addition ERK1 2 is activated by neuronal injury. In damaged cells ERK1 2 activation may act as a dfeensive mechanism that helps to compensate for the deleterious effects of a damaging insult. The emerging mechanisms of ERK1 2-mediated neuroprotection mayinvolve transcriptional regulation and or direct inhibition of cell death machinery. Keywords apoptosis MAP-kinase neurons neuroprotection programmed cell death signal transduction survival. Signaling pathways and neuronal survival Death of neurons occurs during development of the central nervous system CNS . Therefore restriction of neuronal death bysurvival signaling is critical for the proper formation of the CNS 1 . In CNS pathologies including stroke Alzheimer s disease or CNS trauma nerve cell death occurs as a result of cell injury 11 . Consequanely survival signaling cascades mayprovide targets for neuroprotective therapies against these conditions. Neuronal survival signaling involves several pathways including phoshpatidylo-inositol-3-kinase PI3K extracellular signal regulated kinase 1 2 ERK1 2 or extracellular signal regulated kinase 5 ERK5 2 . Interestingly while PI3K .
