Simpkins James W, Yi Kun Don, Yang Shao-Hua
Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science, Fort Worth, TX 76107, USA.
Front Neuroendocrinol. 2009 Jul;30(2):93-105. doi: 10.1016/j.yfrne.2009.04.013. Epub 2009 May 3.
In the present treatise, we provide evidence that the neuroprotective and mito-protective effects of estrogens are inexorably linked and involve the ability of estrogens to maintain mitochondrial function during neurotoxic stress. This is achieved by the induction of nuclear and mitochondrial gene expression, the maintenance of protein phosphatases levels in a manner that likely involves modulation of the phosphorylation state of signaling kinases and mitochondrial pro- and anti-apoptotic proteins, and the potent redox/antioxidant activity of estrogens. These estrogen actions are mediated through a combination of estrogens receptor (ER)-mediated effects on nuclear and mitochondrial transcription of protein vital to mitochondrial function, ER-mediated, non-genomic signaling and non-ER-mediated effects of estrogens on signaling and oxidative stress. Collectively, these multifaceted, coordinated action of estrogens leads to their potency in protecting neurons from a wide variety of acute insults as well as chronic neurodegenerative processes.
在本论文中，我们提供证据表明，雌激素的神经保护和线粒体保护作用紧密相连，且涉及雌激素在神经毒性应激期间维持线粒体功能的能力。这是通过诱导核基因和线粒体基因表达、以可能涉及调节信号激酶以及线粒体促凋亡和抗凋亡蛋白磷酸化状态的方式维持蛋白磷酸酶水平，以及雌激素强大的氧化还原/抗氧化活性来实现的。这些雌激素作用是通过雌激素受体（ER）介导的对线粒体功能至关重要的蛋白质的核转录和线粒体转录的影响、ER介导的非基因组信号传导以及雌激素对信号传导和氧化应激的非ER介导作用共同介导的。总体而言，雌激素的这些多方面、协调的作用使其能够有效保护神经元免受各种急性损伤以及慢性神经退行性过程的影响。
