RT Journal Article SR Electronic T1 Neuroprotection against Oxidative Stress by Estrogens: Structure-Activity Relationship JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 535 OP 541 DO 10.1124/mol.51.4.535 VO 51 IS 4 A1 Behl, Christian A1 Skutella, Thomas A1 Lezoualc’H, Frank A1 Post, Anke A1 Widmann, Martina A1 Newton, Christopher J. A1 Holsboer, Florian YR 1997 UL http://molpharm.aspetjournals.org/content/51/4/535.abstract AB Oxidative stress-induced neuronal cell death has been implicated in different neurological disorders and neurodegenerative diseases; one such ailment is Alzheimer’s disease. Using the Alzheimer’s disease-associated amyloid β protein, glutamate, hydrogen peroxide, and buthionine sulfoximine, we investigated the neuroprotective potential of estrogen against oxidative stress-induced cell death. We show that 17-β-estradiol, its nonestrogenic stereoisomer, 17-α-estradiol, and some estradiol 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 independent of an activation of estrogen receptors.