title: Non-feminizing estrogens: a novel neuroprotective therapy.
abstract: While the conflict between basic science evidence for estrogen neuroprotection and the lack of effectiveness in clinical trials is only now being resolved, it is clear that strategies for estrogen neuroprotection that avoid activation of ERs have the potential for clinical application. Herein we review the evidence from both in vitro and in vivo studies that describe high potency neuroprotection with non-feminizing estrogens. We have characterized many of the essential chemical features of non-feminizing estrogens that eliminate or reduce ER binding while maintaining or enhancing neuroprotection. Additionally, we provide evidence that these non-feminizing estrogens have efficacy in protecting the brain from AD neuropathology and traumatic brain injury. In conclusion, it appears that the non-feminizing estrogen strategy for neuroprotection is a viable option to achieve the beneficial neuroprotective effects of estrogens while eliminating the toxic off-target effects of chronic estrogen administration.
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, United States; Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, WV, United States.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Petrone
authors.affiliation: Department of Emergency Medicine, University of Texas Southwestern Medical School, Dallas, TX, United States.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Gatson
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, United States; Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, WV, United States.
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
authors.affiliation: Center for Basic and Translational Stroke Research, West Virginia University, Morgantown, WV, United States; Department of Psychology, West Virginia University, Morgantown, WV, United States. Electronic address: Miranda.Reed@mail.wvu.edu.
authors.forename: Miranda N
authors.initials: MN
authors.lastname: Reed
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D004967:Estrogens; D018696:Neuroprotective Agents; D011960:Receptors, Estrogen
keywords: Alzheimer’s disease; Estradiol; Estrogen receptors; Neuroprotection; Non-feminizing estrogens; Traumatic brain injury