title: The regulation of catalase activity by PPAR γ is affected by α-synuclein.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University Jerusalem, 91120, Israel.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Yakunin
authors.affiliation: Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University Jerusalem, 91120, Israel.
authors.forename: Haya
authors.initials: H
authors.lastname: Kisos
authors.affiliation: Genetic Metabolic Diseases Lab, Academic Medical Center, University of Amsterdam Amsterdam, 1105 AZ, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Kulik
authors.affiliation: Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University Jerusalem, 91120, Israel.
authors.forename: Jessica
authors.initials: J
authors.lastname: Grigoletto
authors.affiliation: Genetic Metabolic Diseases Lab, Academic Medical Center, University of Amsterdam Amsterdam, 1105 AZ, The Netherlands.
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.affiliation: Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University Jerusalem, 91120, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Sharon