The Effect Of NR4A1 Overexpression On APP Metabolism And Tau Phosphorylation

Objective:To investigate the effect of orphan nuclear receptor NR4A1 expression on APP metabolism and Tau phosphorylation in HT22 cells and its possible mechanisms.Methods:APP/PS1 and WT mice in 18 months were sacrificed after anesthes ia and hippocampus were separated.Western blotting and q RT-PCR analys is were performed to assess the NR4A1 protein and mRNA levels,respectively.Immunohistochemical staining was used to display NR4A1 expression in the hippocampus of mice brain.The HT22 cells were transfected with mouse p CMV-NR4A1 plasmid.The expression of NR4A1,APP,ADAM10,BACE1,t-Tau and p-Tau,GSK3?and p-GSK3?,CDK5 and ERK in transfected HT22 cells were determined by western blotting analys is.NR4A1 mRNA,ADAM10 mRNA,BACE1 mRNA levels in transfected HT22 cells were detected with q RT-PCR.Results:The expression of NR4A1 protein and mRNA were reduced in the hippocampus of APP/PS1 mice.After transfected with NR4A1 in H22 cells,NR4A1 mRNA and protein were overexpressed significantly.The expression of APP,?-CTF,BACE1 protein and mRNA were increased,while ?-CTF,ADAM10 mRNA and protein were down-regulated in HT22 cells transfected with NR4A1.The expression of p-Tau(S396)was increased,p-GSK3? reduced,t-Tau,p-Tau(S262 and T231),CDK5 and ERK were unchanged.Conclusions:NR4A1 overexpression may promote the A? reduction pathway of APP by down-regulating the expression of ADAM10 and up-regulating the expression of BACE1.Moreover,NR4A1 may affect APP metabolism and the phosphorylation of Tau by p-GS3K?.