Protein kinase inhibitor attenuates apoptotic cell death induced by amyloid beta protein in culture of the rat cerebral cortex

Amyloid beta protein (A beta) is deposited characteristically in the brain of patients with Alzheimer's disease. Effects of protein kinase inhibitors (H-89, H-7, KN-62) on A beta-induced neuronal cell death were examined in primary culture of dissociated cerebral cortical cells. beta(25-35), the active fragment of AB, induced neuronal cell death with apoptotic features including chromatin condensation and DNA fragmentation. The cell death was attenuated by cycloheximide or by H-89, a specific protein kinase A (PKA) inhibitor, but not by H-7 or KN-62. These data suggest that beta(25-35) induces apoptotic cell death through the PKA-mediated pathway.