TY - JOUR T1 - Neuroprotection against Oxidative Stress by Estrogens: Structure-Activity Relationship JF - Molecular Pharmacology JO - Mol Pharmacol SP - 535 LP - 541 DO - 10.1124/mol.51.4.535 VL - 51 IS - 4 AU - Christian Behl AU - Thomas Skutella AU - Frank Lezoualc’H AU - Anke Post AU - Martina Widmann AU - Christopher J. Newton AU - Florian Holsboer Y1 - 1997/04/01 UR - http://molpharm.aspetjournals.org/content/51/4/535.abstract N2 - 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. ER -