SUMMARY

Oxidative stress-induced neuronal cell death has been impli-cated in different neurological disorders and neurodegenerative diseases; one such ailment is Alzheimer’s disease. Using the Alzheimer’s disease-associated amyloid b protein, glutamate, hydrogen peroxide, and buthionine sulfoximine, we investi-gated the neuroprotective potential of estrogen against oxida-tive stress-induced cell death. We show that 17-b-estradiol, its nonestrogenic stereoisomer, 17-a-estradiol, and some estra-diol derivatives can prevent intracellular peroxide accumulation and, ultimately, the degeneration of primary neurons, clonal hippocampal cells, and cells in organotypic hippocampal slices. The neuroprotective antioxidant activity of estrogens is dependent on the presence of the hydroxyl group in the C3 position on the A ring of the steroid molecule but is indepen-dent of an activation of estrogen receptors