Division of Brain Sciences, Imperial College London, UK.
IUBMB Life. 2012 Dec;64(12):958-64. doi: 10.1002/iub.1097. Epub 2012 Nov 6.
Peroxisome proliferator-activated receptor-γ (PPARγ) was initially involved in the regulation of glucose and lipid metabolism, cell differentiation, as well as in the transcriptional control of a wide range of inflammatory genes. However, during the last decade, there has been evidence of the implication of this nuclear receptor in neurodegeneration. Various studies have shown that the administration of PPARγ ligands leads to a reduced pathology in many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, and stroke. PPARγ cofactors have a critical function in regulating the activity of PPARγ. Recent reports have brought to light the role of the PPARγ coactivator-1α (PGC-1α) in several neurodegenerative pathologies. However, very little is know about other PPARγ cofactors in the brain, such as the receptor-interacting protein 140, as well as the nuclear receptor corepressor, which seems to be required for normal neural development at specific embryonic stages. In this review, we aim to analyze the role of the main regulators of PPARγ in the brain and during neurodegeneration.
过氧化物酶体增殖物激活受体-γ（PPARγ）最初参与葡萄糖和脂质代谢的调节、细胞分化，以及广泛的炎症基因的转录控制。然而，在过去的十年中，有证据表明这种核受体与神经退行性变有关。各种研究表明，PPARγ 配体的给药导致许多神经退行性疾病（如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症、多发性硬化症、亨廷顿病和中风）的病理减轻。PPARγ 共激活因子在调节 PPARγ 的活性方面具有关键作用。最近的报告揭示了 PPARγ 共激活因子-1α（PGC-1α）在几种神经退行性病理中的作用。然而，对于大脑中的其他 PPARγ 共激活因子，如受体相互作用蛋白 140 以及核受体共抑制因子，人们知之甚少，它们似乎在特定胚胎阶段的正常神经发育中是必需的。在这篇综述中，我们旨在分析大脑中和神经退行性变过程中 PPARγ 的主要调节因子的作用。
