Liang Yu, Zhong Guangshang, Ren Mingxin, Sun Tingting, Li Yangyang, Ye Ming, Ma Caiyun, Guo Yu, Liu Changqing
School of Clinical Medicine, Bengbu Medical College, Bengbu, 233000, China.
School of Life Sciences, Bengbu Medical College, Bengbu, 233000, China.
Neuromolecular Med. 2023 Dec;25(4):471-488. doi: 10.1007/s12017-023-08755-0. Epub 2023 Sep 12.
Parkinson's disease (PD) is a common neurodegenerative disease that is mainly in middle-aged people and elderly people, and the pathogenesis of PD is complex and diverse. The ubiquitin-proteasome system (UPS) is a master regulator of neural development and the maintenance of brain structure and function. Dysfunction of components and substrates of this UPS has been linked to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Moreover, UPS can regulate α-synuclein misfolding and aggregation, mitophagy, neuroinflammation and oxidative stress to affect the development of PD. In the present study, we review the role of several related E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) on the pathogenesis of PD such as Parkin, CHIP, USP8, etc. On this basis, we summarize the connections and differences of different E3 ubiquitin ligases in the pathogenesis, and elaborate on the regulatory progress of different DUBs on the pathogenesis of PD. Therefore, we can better understand their relationships and provide feasible and valuable therapeutic clues for UPS-related PD treatment research.
帕金森病（PD）是一种常见的神经退行性疾病，主要发生于中老年人，其发病机制复杂多样。泛素-蛋白酶体系统（UPS）是神经发育以及脑结构和功能维持的主要调节因子。该UPS的组分和底物功能异常与帕金森病和阿尔茨海默病等神经退行性疾病有关。此外，UPS可调节α-突触核蛋白的错误折叠和聚集、线粒体自噬、神经炎症和氧化应激，从而影响帕金森病的发展。在本研究中，我们综述了几种相关的E3泛素连接酶和去泛素化酶（DUBs）如帕金蛋白（Parkin）、CHIP、USP8等在帕金森病发病机制中的作用。在此基础上，我们总结了不同E3泛素连接酶在发病机制中的联系与差异，并阐述了不同DUBs对帕金森病发病机制的调节进展。因此，我们可以更好地理解它们之间的关系，并为与UPS相关的帕金森病治疗研究提供可行且有价值的治疗线索。
