Faculty of Bioengineering and Bioinformatics and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
J Alzheimers Dis. 2012;28(2):283-9. doi: 10.3233/JAD-2011-111391.
Much experimental evidence suggests that age-related brain pathologies are most often mediated by reactive oxygen species primarily originating from mitochondria (mROS). Two papers with such evidence have been recently published in the Journal of Alzheimer's Disease (Stefanova et al., J Alzheimers Dis 21, 476-491, 2010; Lloret et al., J Alzheimers Dis, doi: 10.3233/JAD-2011-110890). In the first paper, it was shown that appearance of a typical behavioral trait of aging in rats (that old animals do not enter an open arm in a maze) was completely reversed by ten weeks treatment of the old rats with the mitochondria-targeted antioxidant SkQ1. In the second article, the authors identified molecular mechanisms by which amyloid-β-induced mROS can mediate hyperphosphorylation of the tau protein, a key event in Alzheimer's disease. Conventional antioxidants prevented such hyperphosphorylation. In this article, I will summarize the present state of the art in this field. I conclude that mitochondria-targeted rechargeable antioxidants are promising as tools to treat brain pathologies developing in elderly humans.
大量实验证据表明，与年龄相关的脑部病变通常是由主要源自线粒体的活性氧物质（mROS）介导的。最近在《阿尔茨海默病杂志》（Journal of Alzheimer's Disease）上发表了两篇有此类证据的论文（Stefanova 等人，J Alzheimers Dis 21, 476-491, 2010；Lloret 等人，J Alzheimers Dis，doi: 10.3233/JAD-2011-110890）。在第一篇论文中，研究表明，通过用靶向线粒体的抗氧化剂 SkQ1 对老年大鼠进行十周的治疗，大鼠出现了衰老的典型行为特征（即老年动物不在迷宫的开放臂中进入），这一特征完全被逆转了。在第二篇文章中，作者确定了淀粉样β诱导的 mROS 如何介导 tau 蛋白过度磷酸化的分子机制，tau 蛋白过度磷酸化是阿尔茨海默病的关键事件。传统的抗氧化剂可以预防这种过度磷酸化。在本文中，我将总结该领域的最新进展。我得出的结论是，靶向线粒体的可再充电抗氧化剂作为治疗老年人脑病变的工具具有广阔的前景。
