USP14 inhibitor attenuates cerebral ischemia/reperfusion-induced neuronal injury in mice.
USP14 inhibitor attenuates cerebral ischemia/reperfusion-induced neuronal injury in mice.
复制标题
DOI：
10.1111/jnc.13941
复制
发表时间：
2017-03
影响因子：
4.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Min JW;Lü L;Freeling JL;Martin DS;Wang H
中风与错误折叠和聚集蛋白的过度产生有关。然而，在很大程度上仍不清楚缺血性卒中后促进蛋白质聚集体的清除是否具有神经保护作用。脱泛素酶(DUBS)是一大类调节蛋白质降解的蛋白酶。泛素特异性蛋白水解酶14(USP14)是一种与蛋白酶体相关的DUB，负向调节蛋白酶体的活性。在这项研究中，我们研究了USP14的特异性小分子抑制剂IU1对小鼠局灶性脑缺血卒中诱导的小鼠神经元损伤的影响。我们发现IU1治疗减轻了缺血性中风引起的神经元损伤，这反映在IU1治疗的小鼠与对照组小鼠相比，存活率提高，脑梗塞体积减少，神经元丢失减少。此外，IU1治疗与蛋白质聚集体减少和蛋白酶体功能增强有关。这些数据不仅突出了蛋白质动态平衡在脑缺血/再灌注性神经元损伤中的重要性，而且也扩大了DUB抑制剂的治疗作用。
Stroke is associated with over-production of misfolded and aggregating proteins. However, it remains largely unclear whether enhanced removal of protein aggregates following ischemic stroke is neuroprotective. Deubiquitinating enzymes (DUBs) are a large group of proteases that regulate protein degradation. The ubiquitin-specific protease 14 (USP14) is a DUB that is associated with the proteasome and negatively regulates proteasome activity. In this study, we examined the effect of IU1, a specific small molecule inhibitor of USP14, on mouse focal cerebral ischemic stroke-induced neuronal injury in mice. We found that IU1 treatment attenuated ischemic stroke-caused neuronal injury, which was reflected by increased survival rate, reduced infarct volume, as well as decreased neuronal loss in the IU1-treated mice compared to the control-treated mice. Additionally, IU1 treatment is associated with reduced protein aggregates and enhanced proteasome functionality. These data not only highlight the significance of protein homeostasis in cerebral ischemia/reperfusion-induced neuronal injury but also extend the therapeutic role of DUB inhibitors.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Dong, Gaofeng;Callegari, Eduardo A.;Wang, Hongmin
通讯作者：
Wang, Hongmin
影响因子：
13.3
作者：
Wang, Pei;Guan, Yun-Feng;Miao, Chao-Yu
通讯作者：
Miao, Chao-Yu
DOI：
10.1074/mcp.r110.003871
发表时间：
2011-05-01
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Lee, Min Jae;Lee, Byung-Hoon;Finley, Daniel
通讯作者：
Finley, Daniel
影响因子：
8.3
作者：
Atochin, DN;Clark, J;Huang, PL
通讯作者：
Huang, PL