Amyloid β 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 (A beta) 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 A beta neurotoxicity by using cultured rat hippocampal and cortical neurons. Exposure of the cells to A beta (1-20 mu M) resulted in a progressive cell death with no change in phosphorylation of p44/42 MAPK (ERK1/2). Furthermore, A beta-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 AP neurotoxicity. (C) 2000 Elsevier Science Ltd. All rights reserved.