Pharmacological mechanism and structure of ubiquitin proteases associated with depression: A review
Yinxiao Jiang1, Ling Ye2, Kexin Han1
1College of Pharmacy, Anhui University of Chinese Medicine, 230012 Hefei, China; Yangtze Delta Drug Advanced Research Institute, 226100 Nantong, China; Nantong InnoStar Bio-technology Co., Ltd., 226100 Nantong, China.
Abstract:
Depression is one of the most common neurologic diseases. It is associated with multiple factors such as inflammation, NMDAR, GABAR, and monoamine neurotransmitters. Ubiquitin and ubiquitination are responsible for protein degradation. The ubiquitin enzyme system plays an essential role in neuromodulation. At the same time, proteolysis-targeting chimeras (PROTACs), which selectively degrade target proteins based on the ubiquitin enzyme system, have been recognized as the most popular technology for drug development in recent years. Therefore, we reviewed the ubiquitin proteases that have been reported, which are associated with depression. Among them, nine ubiquitin ligase E3s are highlighted. Simultaneously, we summarized the pharmacological mechanism network of E3 ubiquitin ligases. In addition, the structural features of E3 ubiquitin-protein ligases were also reviewed. This review aims to discuss the possibility of developing drugs with ubiquitin and PROTAC technology. Additionally, the study reviews the regulation of the ubiquitin protease system within the mechanistic network of depression.
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