These authors contributed equally to this work
The regulation of catalase activity by PPAR γ is affected by α-synuclein
Article first published online: 17 FEB 2014
© 2014 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Annals of Clinical and Translational Neurology
Volume 1, Issue 3, pages 145–159, March 2014
How to Cite
Yakunin, E., Kisos, H., Kulik, W., Grigoletto, J., Wanders, R. J. A. and Sharon, R. (2014), The regulation of catalase activity by PPAR γ is affected by α-synuclein. Annals of Clinical and Translational Neurology, 1: 145–159. doi: 10.1002/acn3.38
- Issue published online: 14 MAR 2014
- Article first published online: 17 FEB 2014
- Manuscript Accepted: 7 JAN 2014
- Manuscript Revised: 27 DEC 2013
- Manuscript Received: 27 SEP 2013
- Israel Science Foundation. Grant Number: 182/12
- Rosetrees. Grant Number: M90
While evidence for oxidative injury is frequently detected in brains of humans affected by Parkinson's disease (PD) and in relevant animal models, there is uncertainty regarding its cause. We tested the potential role of catalase in the oxidative injury that characterizes PD.
Utilizing brains of A53T α-Syn and ntg mice, and cultured cells, we analyzed catalase activity and expression, and performed biochemical analyses of peroxisomal metabolites.
Lower catalase expression and lower activity levels were detected in A53T α-Syn brains and α-Syn-expressing cells. The effect on catalase activity was independent of disease progression, represented by mouse age and α-Syn mutation, suggesting a potential physiological function for α-Syn. Notably, catalase activity and expression were unaffected in brains of mice modeling Alzheimer's disease. Moreover, we found that α-Syn expression downregulate the peroxisome proliferator-activated receptor (PPAR)γ, which controls catalase transcription. Importantly, activation of either PPARγ2, PPARα or retinoic X receptor eliminated the inhibiting effect of α-Syn on catalase activity. In addition, activation of these nuclear receptors enhanced the accumulation of soluble α-Syn oligomers, resulting in a positive association between the degree of soluble α-Syn oligomers and catalase activity. Of note, a comprehensive biochemical analysis of specific peroxisomal metabolites indicated no signs of dysfunction in specific peroxisomal activities in brains of A53T α-Syn mice.
Our results suggest that α-Syn expression may interfere with the complex and overlapping network of nuclear receptors transcription activation. In result, catalase activity is affected through mechanisms involved in the regulation of soluble α-Syn oligomers.