Estrogen protects neuronal cells from amyloid β-induced apoptotic cell death

Accumulating studies have shown that estrogen replacement therapy reduces the risk of Alzheimer's disease. In this study, we clarified that 17 beta -esrradiol (E2) significantly rescues PC12 neuronal cells from amyloid beta protein (A beta)-induced cell death. We found that the amino acid residues of 25 to 35 (A beta 25-35) were more cytotoxic than the full length protein (A beta1-40) and these residues induced DNA fragmentation typical for apoptosis. In addition, E2 was confirmed to inhibit calcium influx and cytochrome c release induced by A beta 25-35. Since these sequential events cause apoptosis, the protective effect of E2 may be exerted not by the direct interaction with A beta, but by the blockade of the mitochondrial apoptotic pathway induced by A beta. NeuroReport 12:1965-1970 (C) 2001 Lippincott Williams & Wilkins.