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.

中文翻译：

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过氧化物酶体增殖物激活受体 Gamma Co-activator-1 Alpha 作为双相情感障碍和其他神经精神疾病的新靶点

过氧化物酶体增殖物激活受体 gamma coactivator-1 alpha (PGC-1 alpha) 是一种通过激活核受体，尤其是过氧化物酶体增殖物激活受体 (PPAR) 家族来调节代谢和炎症的蛋白质。PGC-1 alpha 和 PPARs 还调节线粒体生物发生、细胞能量产生、产热和脂质代谢。脑能量代谢也可能部分受 PGC-1 α 和 PPAR 之间的相互作用的调节。由于神经退行性疾病（亨廷顿病、帕金森病和肌萎缩侧索硬化）和双相情感障碍与线粒体和脑能量代谢失调有关，PGC-1 α 可能代表这些疾病的潜在药物靶点。本文的目的是回顾 PGC-1 alpha、PPARs、以及 PPAR 激动剂靶向 PGC-1 α 以治疗神经退行性疾病和双相情感障碍的作用。我们还回顾了用于神经退行性疾病和双相情感障碍的重新利用的抗糖尿病噻唑烷和抗甘油三酯（PPAR 激动剂）的临床试验。PGC-1 alpha 和 PPARs 是双相情感障碍的创新潜在目标，值得未来的临床试验。