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Licensed Unlicensed Requires Authentication Published by De Gruyter September 6, 2013

Role of the peroxisome proliferator-activated receptors (PPAR)-α, β/δ and γ triad in regulation of reactive oxygen species signaling in brain

  • Stepan Aleshin

    Stepan Aleshin graduated in 2006 at Biological Department of Moscow State University (MSU), Russian Federation. In 2009 he received his PhD in Biochemistry and Molecular Biology at the Faculty of Bioengineering and Bioinformatics of MSU. Since 2010 he works at the Institute of Neurobiochemistry of Otto-von-Guericke University, Magdeburg as postdoctoral fellow. His main scientific interest is deciphering the mechanisms of roles of Peroxisome Proliferators Activated Receptors (PPAR) in brain diseases.

    and Georg Reiser

    Georg Reiser did his PhD at the Max-Planck Institute of Biochemistry in Martinsried and the Ludwig-Maximilians University in Munich under the supervision of B. Hamprecht in the Department of F. Lynen. After working as research fellow in the Institute for Physiological Chemistry in Wurzburg, he obtained a DFG-fellowship with further training in electrophysiology at the University College London, Department of Biophysics under R. Miledi. There, he studied nicotinic acetylcholine receptor ion channels. From 1984 he continued research in mechanisms of neural molecular signaling, focusing on calcium regulation and identification of the inositol(1,3,4,5)P4 receptor protein. From 1994 he is Professor of Neurochemistry in Magdeburg, Medical Faculty researching on various molecular mechanisms of neuroprotection in ischemia and stroke, covering functions of mitochondria, protease-activated receptors, P2Y nucleotide receptors, nuclear Peroxisome Proliferators Activated Receptors, and iPLA2isoforms.

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From the journal Biological Chemistry

Abstract

Overwhelming evidence shows that oxidative stress is a major cause in development of brain disorders. Low activity of the reactive oxygen species (ROS)-degrading system as well as high levels of oxidative damage markers have been observed in brain tissue of patients with neurodegenerative and other brain diseases to a larger extent than in healthy individuals. Many studies aimed to develop effective and safe antioxidant strategies for the therapy or prevention of brain diseases. Nevertheless, it became clear that rigorous suppression of ROS is deleterious for normal cell functioning. Thus, approaches that can regulate the ROS levels over a wide range, from inhibition to induction, will be a powerful tool for neuroprotection. A most prominent target for such ROS management is the family of peroxisome proliferator-activated receptors (PPARs). All three members (PPAR-α, -β/δ and -γ) of this nuclear receptor subfamily form a tightly connected triad. For individual PPAR isoforms, neuroprotective properties have been well proven. Their involvement in regulation of ROS production and degradation underlies the therapeutic effects. Nevertheless, the current paradigms of the involvement of PPAR in neuroprotective therapy ignore such interconnections of PPARs and aim at antioxidant effects of individual PPAR isoforms, but do not take into account the necessity of careful regulation of ROS levels. The present review (i) summarizes the data, which support the concept of the PPAR triad in brain, (ii) demonstrates that usage of the PPAR triad allows the regulation of PPAR-dependent genes over a wide range, from inhibition to upregulation, and (iii) summarizes the known data concerning the PPAR triad involvement in regulation of ROS. Our report opens new directions in the field of PPAR/ROS-related neuroscience research.


Corresponding author: Georg Reiser, Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Neurobiochemie, Leipziger Straße 44, D-39120 Magdeburg, Germany, e-mail:

About the authors

Stepan Aleshin

Stepan Aleshin graduated in 2006 at Biological Department of Moscow State University (MSU), Russian Federation. In 2009 he received his PhD in Biochemistry and Molecular Biology at the Faculty of Bioengineering and Bioinformatics of MSU. Since 2010 he works at the Institute of Neurobiochemistry of Otto-von-Guericke University, Magdeburg as postdoctoral fellow. His main scientific interest is deciphering the mechanisms of roles of Peroxisome Proliferators Activated Receptors (PPAR) in brain diseases.

Georg Reiser

Georg Reiser did his PhD at the Max-Planck Institute of Biochemistry in Martinsried and the Ludwig-Maximilians University in Munich under the supervision of B. Hamprecht in the Department of F. Lynen. After working as research fellow in the Institute for Physiological Chemistry in Wurzburg, he obtained a DFG-fellowship with further training in electrophysiology at the University College London, Department of Biophysics under R. Miledi. There, he studied nicotinic acetylcholine receptor ion channels. From 1984 he continued research in mechanisms of neural molecular signaling, focusing on calcium regulation and identification of the inositol(1,3,4,5)P4 receptor protein. From 1994 he is Professor of Neurochemistry in Magdeburg, Medical Faculty researching on various molecular mechanisms of neuroprotection in ischemia and stroke, covering functions of mitochondria, protease-activated receptors, P2Y nucleotide receptors, nuclear Peroxisome Proliferators Activated Receptors, and iPLA2isoforms.

The study in the authors’ laboratory was supported by grants from Bundesministerium für Bildung und Forschung (BMBF).

Conflict of interest statement

None to declare.

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Received: 2013-6-28
Accepted: 2013-9-4
Published Online: 2013-09-06
Published in Print: 2013-12-01

©2013 by Walter de Gruyter Berlin Boston

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