Abstract
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.
Footnotes
- Received November 6, 1996.
- Accepted January 2, 1997.
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Send reprint requests to: Christian Behl, Max Planck Institute of Psychiatry, Clinical Institute, 80804 Munich, Germany. E-mail: chris{at}mpipsykl.mpg.de
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F.L. was supported by a postdoctoral fellowship from Institute National de la Santé et de la Recherche Médicale. This work was supported in part by a grant of the Wilhelm-Woort-Stiftung für Alternsforschung (C.B.).
- The American Society for Pharmacology and Experimental Therapeutics
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