Idebenone and resveratrol extend lifespan and improve motor function of HtrA2 knockout mice..pdf (337.88 kB)
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Idebenone and resveratrol extend lifespan and improve motor function of HtrA2 knockout mice

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journal contribution
posted on 21.04.2016, 09:59 by E. Gerhardt, S. Gräber, E. M. Szego, N. Moisoi, L. Miguel Martins, T. F. Outeiro, P. Kermer
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.

History

Citation

PLoS One, 2011, 6 (12), e28855

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Old Departments Pre 01 Aug 2015/Department of Cell Physiology and Pharmacology (Pre 01 Aug 2015)

Version

VoR (Version of Record)

Published in

PLoS One

Publisher

Public Library of Science

eissn

1932-6203

Acceptance date

16/11/2011

Copyright date

2011

Available date

21/04/2016

Publisher version

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028855

Language

en