中文摘要：

目的：在细胞水平探讨泛素C末端水解酶L1（UCH-L1）活性抑制对微管相关蛋白tau的磷酸化影响。方法：使用UCH-L1特异性抑制剂LDN-57444处理原代培养皮层神经元后检测UCH-L1酶活性,tau蛋白磷酸化水平采用免疫印记法检测。结果：LDN-57444对UCH-L1酶活性的抑制呈浓度依赖性和时间依赖性关系（P〈0.01）;伴随UCH-L1酶活性的显著抑制,tau蛋白Ser199、Ser202和Ser396位点磷酸化水平均明显升高（P〈0.01）,而总tau水平无明显改变（P〉0.05）。结论：UCH-L1抑制可诱发神经元过度磷酸化tau蛋白的聚积,UCH-L1活性失调可能参与了阿尔茨海默病的病理过程。

英文摘要：

Objective：To investigate the effects of ubiquitin carboxy-terminal hydrolase L1（UCH-L1）activity on tau phosphorylation in primary cortical neuron cultures.Methods：The primary cortical neuron cultures were treated with LDN-57444,the specific inhibitor of UCH-L1.The activity of UCH-L1 in the neuron was determined,and the level of tau phosphorylation was detected by Western blot.Results：With the evident inhibition of UCH-L1 activity,the levels of tau phosphorylation at the sites of Ser199,Ser202 and Ser396 were significantly increased（P〈0.01）,while the level of total tau was not changed（P〉0.05）.Conclusions：Inhibition of UCH-L1 could induce the accumulation of hyperphosphorylated tau in the primary cultured neurons.UCH-L1 dysfunction might be involved in the pathogenesis of Alzheimer＇s disease.