Authors: Xiao-Wen Zhang, Na Feng, Yan-Chen Liu, Qiang Guo, Jing-Kang Wang, Yi-Zhen Bai, Xiao-Ming Ye, Zhuo Yang, Heng Yang, Yang Liu, Mi-Mi Yang, Yan-Hang Wang, Xiao-Meng Shi, Dan Liu, Peng-Fei Tu, Ke-Wu Zeng
Published: 2022-08-10
Source: Full article
Neuroinflammation is a fundamental contributor to progressive neuronal damage, which arouses a heightened interest in neurodegenerative disease therapy. Ubiquitin-specific protease 7 (USP7) has a crucial role in regulating protein stability in multiple biological processes; however, the potential role of USP7 in neurodegenerative progression is poorly understood. Here, we discover the natural small molecule eupalinolide B (EB), which targets USP7 to inhibit microglia activation. Cocrystal structure reveals a previously undisclosed covalent allosteric site, Cys