Tang Mi-Bo, Liu Yi-Xuan, Hu Zheng-Wei, Luo Hai-Yang, Zhang Shuo, Shi Chang-He, Xu Yu-Ming
Department of Geriatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Front Aging Neurosci. 2025 Feb 12;16:1454735. doi: 10.3389/fnagi.2024.1454735. eCollection 2024.
Peroxisome proliferator-activated receptor- coactivator-1α (PGC-1α), which is highly expressed in the central nervous system, is known to be involved in the regulation of mitochondrial biosynthesis, metabolic regulation, neuroinflammation, autophagy, and oxidative stress. This knowledge indicates a potential role of PGC-1α in a wide range of functions associated with neurological diseases. There is emerging evidence indicating a protective role of PGC-1α in the pathogenesis of several neurological diseases. As such, a deeper and broader understanding of PGC-1α and its role in neurological diseases is urgently needed. The present review provides a relatively complete overview of the current knowledge on PGC-1α, including its functions in different types of neurons, basic structural characteristics, and its interacting transcription factors. Furthermore, we present the role of PGC-1α in the pathogenesis of various neurological diseases, such as intracerebral hemorrhage, ischemic stroke, Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and other PolyQ diseases. Importantly, we discuss some compounds or drug-targeting strategies that have been studied to ameliorate the pathology of these neurological diseases and introduce the possible mechanistic pathways. Based on the available studies, we propose that targeting PGC-1α could serve as a promising novel therapeutic strategy for one or more neurological diseases.
过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)在中枢神经系统中高表达,已知其参与线粒体生物合成、代谢调节、神经炎症、自噬和氧化应激的调控。这表明PGC-1α在与神经疾病相关的广泛功能中具有潜在作用。越来越多的证据表明PGC-1α在几种神经疾病的发病机制中具有保护作用。因此,迫切需要对PGC-1α及其在神经疾病中的作用进行更深入、更广泛的了解。本综述提供了关于PGC-1α当前知识的相对完整概述,包括其在不同类型神经元中的功能、基本结构特征及其相互作用的转录因子。此外,我们阐述了PGC-1α在各种神经疾病发病机制中的作用,如脑出血、缺血性中风、阿尔茨海默病、帕金森病、肌萎缩侧索硬化症、亨廷顿病和其他多聚谷氨酰胺疾病。重要的是,我们讨论了一些已研究的用于改善这些神经疾病病理的化合物或药物靶向策略,并介绍了可能的作用机制途径。基于现有研究,我们提出靶向PGC-1α可能成为一种有前景的针对一种或多种神经疾病的新型治疗策略。