title: Neuroprotection with non-feminizing estrogen analogues: an overlooked possible therapeutic strategy.
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.
authors.affiliation: 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
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Richardson
authors.forename: Kun Don
authors.initials: KD
authors.lastname: Yi
authors.forename: Evelyn
authors.initials: E
authors.lastname: Perez
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Covey
mesh_terms: D000818:Animals; D019610:Cytoprotection / Q000187:drug effects*; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D045166:Estradiol Congeners / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005262:Feminization / Q000139:chemically induced / Q000517:prevention & control*; D005621:Friedreich Ataxia / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008297:Male; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D045166:Estradiol Congeners; D018696:Neuroprotective Agents