Neurochemical Research 2003-02-01

Discussion of the role of the extracellular signal-regulated kinase-phospholipase A2 pathway in production of reactive oxygen species in Alzheimer's disease.

Jannike M Andersen, Oddvar Myhre, Frode Fonnum

Index: Neurochem. Res. 28(2) , 319-26, (2003)

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Abstract

In this paper we show that exposure of a rat brain synaptosome fraction to the amyloid beta peptide fragment betaA(25-35), but not the inverted peptide betaA(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 betaA(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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