Caspase-8 Mediates Amyloid-β-induced Apoptosis in Differentiated PC12 Cells.

The pathogenesis of Alzheimer's disease (AD) is very complex and there are currently no significant treatments for the disease. Caspase-8 is known to be involved in neuronal apoptosis. To explore a possible molecular mechanisms involved in AD pathology, this study investigated the effect of caspase-8 knockdown on amyloid-β 1-40 (Aβ1-40)-induced apoptosis in PC12 cells. The proliferation of PC12 cells was significantly inhibited in Aβ-treated cells, and a high fraction of the cells underwent apoptosis in a dose- and time-dependent manner. Transfection of caspase-8 small interfering RNA (siRNA) resulted in reduced apoptosis following Aβ1-40 treatment. The activation of caspase-3, caspase-8, and caspase-9 was stimulated by Aβ1-40, an effect that was also significantly reduced by caspase-8 siRNA. Knockdown of caspase-8 increased the phosphorylation of the signaling molecules AKT and ERK1/2 relative to cells treated with Aβ1-40 alone. Caspase-8 is an important effector molecule involved in apoptosis induced by Aβ1-40 and is likely involved in AD pathology. This study suggests that targeted inhibition of caspase-8 may be a new therapeutic for preventing neuronal apoptosis and inhibiting the progression of AD.