Neuroprotective effects of estrogen against beta-amyloid toxicity are mediated by estrogen receptors in cultured neuronal cells

Although estrogen is known to exert beneficial effects on Alzheimer's disea se, its underlying cellular mechanisms have not been clear. In this study w e investigated whether or not neuroprotective effects of estrogen are media ted by estrogen receptors (ERs). Treatment of estrogen (1.8 nM) reduced bet a-amyloid (A beta)-induced death of ER-expressing W4 cells. This effect of estrogen was blocked by a specific ER blocker ICI 182,780. When estrogen wa s treated to HT22 cells, which lack functional ERs, A beta -induced cell de ath was not affected. Transfection of HT22 cells with human ER alpha, but n ot ERP, restored protective action of estrogen against A beta. Hoechst stai ning revealed that estrogen protected ER alpha -expressing cells by blockin g A beta -induced apoptosis. These results indicate that estrogen blocks A beta -induced cell death via ER alpha -dependent pathways. (C) 2001 Elsevie r Science Ireland Ltd. All rights reserved.