Amyloid beta neurotoxicity not mediated by the mitogen-activated protein kinase cascade in cultured rat hippocampal and cortical neurons.

It has recently been reported that Alzheimer's disease amyloid beta protein (Abeta) activates the mitogen-activated protein kinase (MAPK) cascade in certain types of cells. In the present study, we investigated whether this signal transduction cascade is involved in Abeta neurotoxicity by using cultured rat hippocampal and cortical neurons. Exposure of the cells to Abeta (1-20microM) resulted in a progressive cell death with no change in phosphorylation of p44/42 MAPK (ERK1/2). Furthermore, Abeta-induced neuronal death was not at all affected by U0126 and PD98059, inhibitors of the MAPK-activating enzyme MEK. These results suggest that the MEK/ERK signal transduction cascade is not crucial for Abeta neurotoxicity.