Abstract: Objective To investigate the effects and mechanisms of Loganin on tau phosphorylation.Methods Human neuroblastoma SK-N-SH cells were pre-incubated with Loganin (500 μmol/L,1 000 μmol/L, respectively) for 24 h, and then exposed to 10 μmol/L WT and 10 μmol/L GFX for 3 h after washing out Loganin. Western blotting was used to measure the phosphorylation level of tau protein at Thr205, Thr217, PHF-1 sites, glycogen synthase kinase 3β (GSK-3β), protein phosphatase 2A catalytic subunit C (PP2Ac) and the related proteins in the signaling pathway. Results WT/GFX inhibited the phosphorylation of GSK-3β-ser9, increased tau phosphorylation in SK-N-SH cells. Pre-incubation with Loganin significantly attenuated hyperphosphorylation of tau at Thr205,Thr217,PHF-1 sites in the model cells. Loganin did not reverse the decrease in p-GSK3β-ser9 induced by WT/GFX, suggesting that the effect of Loganin's inhibiting tau hyperphosphorylation may be independent of GSK-3β pathway. However, Loganin reduced the phosphorylation of PP2Ac at Tyr307, but not demethylation of PP2Ac at Leu309 in the WT/GFX-treated cells. Conclusion Loganin attenuated the hyperphosphorylation of tau at multiple sites by reducing the phosphorylation of PP2Ac in Alzheimer's disease-like cell model, independent of regulating GSK-3β.

Key words: Loganin, tau hyperphosphorylation, glycogen synthase kinase-3β, protein phosphatase 2A, Alzheimer's disease