Petrone Ashley B, Gatson Joshua W, Simpkins James W, Reed Miranda N
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.
Department of Emergency Medicine, University of Texas Southwestern Medical School, Dallas, TX, United States.
Mol Cell Endocrinol. 2014 May 25;389(1-2):40-7. doi: 10.1016/j.mce.2013.12.017. Epub 2014 Jan 11.
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.
虽然雌激素神经保护的基础科学证据与临床试验中缺乏有效性之间的冲突直到现在才得到解决，但很明显，避免激活雌激素受体（ERs）的雌激素神经保护策略具有临床应用潜力。在此，我们回顾了来自体外和体内研究的证据，这些证据描述了非雌性化雌激素具有高效的神经保护作用。我们已经确定了许多非雌性化雌激素的基本化学特征，这些特征在维持或增强神经保护作用的同时，消除或减少了与雌激素受体的结合。此外，我们提供的证据表明，这些非雌性化雌激素在保护大脑免受阿尔茨海默病神经病理学和创伤性脑损伤方面具有功效。总之，非雌性化雌激素神经保护策略似乎是一种可行的选择，既能实现雌激素有益的神经保护作用，又能消除长期使用雌激素产生的有害脱靶效应。
