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PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease.

Corona, JC; Duchen, MR; (2016) PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease. Free Radical Biology & Medicine , 100 pp. 153-163. 10.1016/j.freeradbiomed.2016.06.023. Green open access

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Abstract

There is increasing evidence for the involvement of mitochondrial dysfunction and oxidative stress in the pathogenesis of many of the major neurodegenerative and neuroinflammatory diseases, suggesting that mitochondrial and antioxidant pathways may represent potential novel therapeutic targets. Recent years have seen a rapidly growing interest in the use of therapeutic strategies that can limit the defects in, or even to restore, mitochondrial function while reducing free radical generation. The peroxisome proliferation-activated receptor gamma (PPARγ), a ligand-activated transcription factor, has a wide spectrum of biological functions, regulating mitochondrial function, mitochondrial turnover, energy metabolism, antioxidant defence and redox balance, immune responses and fatty acid oxidation. In this review, we explore the evidence for potential beneficial effects of PPARγ agonists in a number of neurological disorders, including Parkinson's disease, Alzheimer's disease, Amyotrophic lateral sclerosis and Huntington's disease, ischaemia, autoimmune encephalomyelitis and neuropathic pain. We discuss the mechanisms underlying those beneficial effects in particular in relation to mitochondrial function, antioxidant defence, cell death and inflammation, and suggest that the PPARγ agonists show significant promise as therapeutic agents in otherwise intractable neurological disease.

Type: Article
Title: PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.freeradbiomed.2016.06.023
Publisher version: http://dx.doi.org/10.1016/j.freeradbiomed.2016.06....
Language: English
Additional information: © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Neuroprotection, PPARγ agonists, mitochondrial function, neurodegenerative disorders
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1502524
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