Bee Venom Phospholipase A2 Reduces Tau Phosphorylation through Inhibition of GSK3β Expression

Author(s): Seung Sik Yoo, Sang-Bae Han, Jaesuk Yun, In Jun Yeo, Hyeon Joo Ham, Yeonjoo Kim, Dong Ju Son, Eui Suk Park, Hae In Rhee, Dae-Youn Hwang, Pil-Hoon Park, Dong-Young Choi, Won-Kyu Lee, Jin Tae Hong

Alzheimer's Disease (AD) is characterized by neuronal cell death and neuroinflammation. Neurofibrillary tangles (NFTs) are neuropathological hallmarks of AD. In this study, we investigated whether that phospholipase A2 (PLA2) reduces tau phosphorylation and neuroinflammation and thus ameliorates AD development. To validate pathological activities in vivo, we examined of the inhibitory effect of bee venom PLA2 (bvPLA2) on memory loss and tau phosphorylation as well as neuroinflammation by subcutaneous injection of bvPLA2 (0.5 mg/kg) in Tg2576 mice. For the in vitro study, we examined the effect of bvPLA2 on cell death, tau pathology and neuroinflammation by treating LPS-activated PC12 cells with bvPLA2. Our study showed that bvPLA2 mitigated memory impairment and spatial memory in Tg2576 mice, In association with memory improvement, tau levels and phosphorylation were decreased by bvPLA2 treatment. The expression levels of pro-inflammatory cytokines and inflammation-related proteins were also decreased in the brains of bvPLA2-treated Tg2576 mice. Considering the reduced tau levels and phosphorylation, GSK3β phosphorylation was also studied. Phosphorylation of GSK3β on Ser9 was significantly increased by treatment with bvPLA2, but phosphorylation of GSK3β on Tyr216 was significantly decreased in brains of Tg2576 mice. These data thus indicate that bvPLA2 prevents memory impairment through reduction of tau phosphorylation.