Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/37421
Title: Idebenone and resveratrol extend lifespan and improve motor function of HtrA2 knockout mice
Authors: Gerhardt, E.
Gräber, S.
Szego, E. M.
Moisoi, N.
Martins, L. Miguel
Outeiro, T. F.
Kermer, P.
First Published: 19-Dec-2011
Publisher: Public Library of Science
Citation: PLoS One, 2011, 6 (12), e28855
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 Resveratrol, a bioactive compound extracted from grapes, are both able to ameliorate this phenotype. Feeding HtrA2 knockout mice with either compound extends lifespan and delays worsening of the motor phenotype. Experiments conducted in cell culture and on brain tissue of mice revealed that each compound has a different mechanism of action. While Idebenone acts by downregulating the integrated stress response, Resveratrol acts by attenuating apoptosis at the level of Bax. These activities can account for the delay in neuronal degeneration in the striata of these mice and illustrate the potential of these compounds as effective therapeutic approaches against neurodegenerative disorders such as HD or PD.
DOI Link: 10.1371/journal.pone.0028855
eISSN: 1932-6203
Links: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028855
http://hdl.handle.net/2381/37421
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2011 Gerhardt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, MRC Toxicology Unit

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