The regulation of catalase activity by PPAR γ is affected by α‐synuclein. (17th February 2014)

• Record Type: Journal Article
• Authors: Yakunin, Eugenia; Kisos, Haya; Kulik, Willem; Grigoletto, Jessica; Wanders, Ronald J. A.; Sharon, Ronit
• Is Part Of: Annals of clinical and translational neurology. Volume 1:Number 3(2014:Mar.)
• Page Start: 145
• Page End: 159
• Publication Date: 2014-02-17
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.38
• Languages: English
• ISSNs: 2328-9503

Abstract

<abstract abstract-type="main" id="acn338-abs-0001"> <title>Abstract</title> <sec id="acn338-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="acn338-sec-0002" sec-type="section"> <title>Methods</title> <p>Utilizing brains of A53T <italic>α</italic>‐Syn and ntg mice, and cultured cells, we analyzed catalase activity and expression, and performed biochemical analyses of peroxisomal metabolites.</p> </sec> <sec id="acn338-sec-0003" sec-type="section"> <title>Results</title> <p>Lower catalase expression and lower activity levels were detected in A53T <italic>α</italic>‐Syn brains and <italic>α</italic>‐Syn‐expressing cells. The effect on catalase activity was independent of disease progression, represented by mouse age and <italic>α</italic>‐Syn mutation, suggesting a potential physiological function for <italic>α</italic>‐Syn. Notably, catalase activity and expression were unaffected in brains of mice modeling Alzheimer's disease. Moreover, we found that <italic>α</italic>‐Syn expression downregulate the peroxisome proliferator‐activated receptor (PPAR)<italic>γ</italic>, which controls catalase transcription. Importantly, activation of either PPAR<italic>γ</italic>2, PPAR<italic>α</italic> or retinoic X receptor eliminated the inhibiting effect of <italic>α</italic>‐Syn on catalase activity. In addition, activation of these nuclear receptors enhanced the accumulation of soluble <italic>α</italic>‐Syn oligomers, resulting in a positive association between the degree of soluble <italic>α</italic>‐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 <italic>α</italic>‐Syn mice.</p> </sec> <sec id="acn338-sec-0004" sec-type="section"> <title>Interpretation</title> <p>Our results suggest that <italic>α</italic>‐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 <italic>α</italic>‐Syn oligomers.</p> </sec> </abstract>