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Horm Behav. 2013 Feb;63(2):278-83. doi: 10.1016/j.yhbeh.2012.03.013. Epub 2012 Apr 3.

Neuroprotection with non-feminizing estrogen analogues: an overlooked possible therapeutic strategy.

Author information

1
Institute for Aging and Alzheimer's Disease Research, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. James.simpkins@unthsc.edu

Abstract

Although many of the effects of estrogens on the brain are mediated through estrogen receptors (ERs), there is evidence that neuroprotective activity of estrogens can be mediated by non-ER mechanisms. Herein, we review the substantial evidence that estrogens neuroprotection is in large part non-ER mediated and describe in vitro and in vivo studies that support this conclusion. Also, we described our drug discovery strategy for capitalizing on enhancement in neuroprotection while at the same time, reducing ER binding of a group of synthetic non-feminizing estrogens. Finally, we offer evidence that part of the neuroprotection of these non-feminizing estrogens is due to enhancement in redox potential of the synthesized compounds.

PMID:
22498694
PMCID:
PMC4446729
DOI:
10.1016/j.yhbeh.2012.03.013
[Indexed for MEDLINE]
Free PMC Article
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