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 b rain of patients with Alzheimer's disease. Effects of protein kinase i nhibitors (H-89, H-7, KN-62) on A beta-induced neuronal cell death wer e examined in primary culture of dissociated cerebral cortical cells. beta(25-35), the active fragment of AB, induced neuronal cell death wi th apoptotic features including chromatin condensation and DNA fragmen tation. The cell death was attenuated by cycloheximide or by H-89, a s pecific protein kinase A (PKA) inhibitor, but not by H-7 or KN-62. The se data suggest that beta(25-35) induces apoptotic cell death through the PKA-mediated pathway.