Influence of presenilin 1 overexpression on endogenous tau phosphorylation in neuroblastoma cells / 复旦学报（医学版）

ABSTRACT

Purpose To study the effect of overexpressing either wild type or a familial Alzheimer disease mutant presenilin 1 (mPS1) on tau phosphorylation in neuroblastoma NG-108 cells. Methods Three different plasmids transfected NG-108 cells respectively. Immunostaining and confocal microscopic technique were used to study the distribution of presenilin 1 and phosphorylated tau. Immunoblot test was applied to investigate the change of tau phosphorylation. Results Immunostaining showed that in brain of sporadic Alzheimer disease, PS1 mainly distributed in neuron and partially colocalized with the phosphorylated tau. Immunoblot tests showed that the cells transected either wild type PS1 or mPS1 contained more phorphorylated tau than the control cells. However, MTT test showed no significant difference between mock transfected cells and the wPS1 or mPS1 transfected cells. In addition, after transfection of the constructed PS1-EGFP vector, overexpressed EGFP-PS1 was located at cell surface membrane and subcellular organelles at earlier time at 12 hr, then EGFP-PS1 diffused in cytosol. Immunocytochemical observations demonstrated that some of the PS1-EGFP transfected cells contained more phosphorylated tau protein, which formed aggresome with PS-1-EGFP. When treated with phosphotase inhibitor okadaic acid, in the PS1-EGFP transfected cells accumulated more phosphorylated tau than the un-transfected cells. Conclusions Wild type PS1 is possibly involved in tauopathy in sporadic Alzheimer's disease.