Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators - PubMed (original) (raw)

. 2006 Oct 20;127(2):397-408.

doi: 10.1016/j.cell.2006.09.024.

Stavit Drori, Marc Uldry, Jessica M Silvaggi, James Rhee, Sibylle Jäger, Christoph Handschin, Kangni Zheng, Jiandie Lin, Wenli Yang, David K Simon, Robert Bachoo, Bruce M Spiegelman

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• PMID: 17055439
• DOI: 10.1016/j.cell.2006.09.024

Free article

Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators

Julie St-Pierre et al. Cell. 2006.

Free article

Abstract

PPARgamma coactivator 1alpha (PGC-1alpha) is a potent stimulator of mitochondrial biogenesis and respiration. Since the mitochondrial electron transport chain is the main producer of reactive oxygen species (ROS) in most cells, we examined the effect of PGC-1alpha on the metabolism of ROS. PGC-1alpha is coinduced with several key ROS-detoxifying enzymes upon treatment of cells with an oxidative stressor; studies with RNAi or null cells indicate that PGC-1alpha is required for the induction of many ROS-detoxifying enzymes, including GPx1 and SOD2. PGC-1alpha null mice are much more sensitive to the neurodegenerative effects of MPTP and kainic acid, oxidative stressors affecting the substantia nigra and hippocampus, respectively. Increasing PGC-1alpha levels dramatically protects neural cells in culture from oxidative-stressor-mediated death. These studies reveal that PGC-1alpha is a broad and powerful regulator of ROS metabolism, providing a potential target for the therapeutic manipulation of these important endogenous toxins.

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• PGC-1alpha, a new therapeutic target in Huntington's disease?
  McGill JK, Beal MF. McGill JK, et al. Cell. 2006 Nov 3;127(3):465-8. doi: 10.1016/j.cell.2006.10.023. Cell. 2006. PMID: 17081970 Review.

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