idebenone and resveratrol extend lifespan and improve motor function of htra2 knockout mice等物质白藜芦醇延长寿命和改善运动机能htra2基因敲除小鼠.pdfVIP

Idebenone and Resveratrol Extend Lifespan and Improve Motor Function of HtrA2 Knockout Mice 1 . ¨ 2. ´ 1 3 3 Ellen Gerhardt * , Simone Graber , Eva M. Szego˝ , Nicoleta Moisoi , L. Miguel Martins , Tiago F. Outeiro1, Pawel Kermer4 ¨ 1 Department of NeuroDegeneration and Restorative Research, DFG Research Center: Molecular Physiology of the Brain, University Medicine Gottingen, Georg-August ¨ ¨ University, Gottingen, Germany, 2 High Throughput Screening Unit, Leibniz-Institut fur Molekulare Pharmakologie, Berlin, Germany, 3 Cell Death Regulation Laboratory, Toxicology Unit , Medical Research Council, Leicester, United Kingdom, 4 Department of Neurology, DFG Research Center: Molecular Physiology of the Brain, University ¨ ¨ Medicine Gottingen, Gottingen, Germany Abstract Heterozygous loss-of-function mutation of the human gene for the mitochondrial protease HtrA2 has been associated with increased risk to develop mitochondrial dysfunction, a process known to contribute to neurodegenerative disorders such as Huntington’s disease (HD) and Parkinson’s disease (PD). Knockout of HtrA2 in mice also leads to mitochondrial dysfunction and to phenotypes that resemble those found in neurodegenerative disorders and, ultimately, lead to death of animals around postnatal day 30. Here, we show that Idebenone, a synthetic antioxidant of the coenzyme Q family, and Resveratr