Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha as a Novel Target for Bipolar Disorder and Other Neuropsychiatric Disorders

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial...

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Bibliographic Details
Published in:Biological psychiatry (1969) 2018-05, Vol.83 (9), p.761-769
Main Authors: Nierenberg, Andrew A., Ghaznavi, Sharmin A., Sande Mathias, Isadora, Ellard, Kristen K., Janos, Jessica A., Sylvia, Louisa G.
Format: Article
Language:English
Subjects:
Bipolar
Bipolar Disorder - drug therapy
Bipolar Disorder - metabolism
Energy
Humans
Lipid metabolism
Neurodegenerative Diseases - drug therapy
Neurodegenerative Diseases - metabolism
Neurodegenerative disorders
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - drug effects
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
Peroxisome Proliferator-Activated Receptors - agonists
Peroxisome Proliferator-Activated Receptors - drug effects
Peroxisome Proliferator-Activated Receptors - metabolism
PGC-1 alpha
PPAR
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Summary:Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions. The purpose of this article is to review the physiology of PGC-1 alpha, PPARs, and the role of PPAR agonists to target PGC-1 alpha to treat neurodegenerative diseases and bipolar disorder. We also review clinical trials of repurposed antidiabetic thiazolidines and anti–triglyceride fibrates (PPAR agonists) for neurodegenerative diseases and bipolar disorder. PGC-1 alpha and PPARs are innovative potential targets for bipolar disorder and warrant future clinical trials.
ISSN:0006-3223
1873-2402
DOI:10.1016/j.biopsych.2017.12.014