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Free Radic Biol Med. 2016 Nov;100:153-163. doi: 10.1016/j.freeradbiomed.2016.06.023. Epub 2016 Jun 25.

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

Author information

1
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom; Laboratory of Neurosciences, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.
2
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom. Electronic address: m.duchen@ucl.ac.uk.

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.

KEYWORDS:

Mitochondrial function; Neurodegenerative disorders; Neuroprotection; PPARγ agonists

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