Abstract: 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.