NEUROPROTECTION AGAINST OXIDATIVE STRESS BY ESTROGENS - STRUCTURE-ACTIVITY RELATIONSHIP

Oxidative stress-induced neuronal cell death has been implicated in di fferent neurological disorders and neurodegenerative diseases; one suc h ailment is Alzheimer's disease. Using the Alzheimer's disease-associ ated amyloid beta protein, glutamate, hydrogen peroxide, and buthionin e sulfoximine, we investigated the neuroprotective potential of estrog en against oxidative stress-induced cell death. We show that 17-beta-e stradiol, its nonestrogenic stereoisomer, 17-alpha-estradiol, and same estradiet derivatives can prevent intracellular peroxide accumulation and, ultimately, the degeneration of primary neurons, clonal hippocam pal cells, and cells in organotypic hippocampal slices. The neuroprote ctive antioxidant activity of estrogens is dependent on the presence o f the hydroxyl group in the C3 position on the A ring of the steroid m olecule but is independent of an activation of estrogen receptors.