Mitochondria-targeted antioxidants as promising drugs for treatment of age-related brain diseases.

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.