Discussion of the role of the extracellular signal-regulated kinase-phospholipase A2 pathway in production of reactive oxygen species in Alzheimer's disease |
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Authors: | Andersen Jannike M Myhre Oddvar Fonnum Frode |
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Affiliation: | (1) Norwegian Defence Research Establishment, P.O. Box 25, N-2027 Kjeller, Norway |
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Abstract: | In this paper we show that exposure of a rat brain synaptosome fraction to the amyloid beta peptide fragment A(25-35), but not the inverted peptide A(35-25), stimulated production of reactive oxygen species (ROS) in a concentration- and time-dependent manner. The ROS formation was attenuated by the tyrosine kinase inhibitor genistein, the mitogen-activated protein kinase inhibitor U0126, and the phospholipase A2 (PLA2) inhibitor 7,7-dimethyl-(5Z,8Z)-eicosadienoic acid. This strongly suggests that A(25-35) stimulated ROS production through an extracellular signal-regulated kinase-PLA2-dependent pathway. The interaction between these enzymes and their possible involvement in free radical formation in Alzheimer's disease are discussed. |
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Keywords: | Amyloid extracellular signal-regulated kinase 1 and 2 phospholipase A2 reactive oxygen species Alzheimer's disease |
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