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

Abstract

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.

• Authors: Andrew A Nierenberg, Sharmin A Ghaznavi, Isadora Sande Mathias, Kristen K Ellard, Jessica A Janos, Louisa G Sylvia
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 83 Issue 9 Pg. 761-769 (05 01 2018) ISSN: 1873-2402 [Electronic] United States
• PMID: 29502862 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• PPARGC1A protein, human
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Peroxisome Proliferator-Activated Receptors

Topics

• Bipolar Disorder (drug therapy, metabolism)
• Humans
• Neurodegenerative Diseases (drug therapy, metabolism)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (drug effects, metabolism)
• Peroxisome Proliferator-Activated Receptors (agonists, drug effects, metabolism)