Bee Venom Phospholipase A2 reduces Tau phosphorylation through inhibition of GSK3β expression

Background Alzheimer's disease (AD) is characterized by to neuronal cell death and neuroinflammation. Neurofibrillary tangle (NFTs) is one of the neuropathological hallmarker of AD. Also our previous study indicated that bee venom leads to neuroprotective effects in a lipopolysaccharide (LPS)-induced AD mouse model. Thus, in this study we investigated whether that phospholipase A2 (PLA2) reduces tau phosphorylation and neuroinflammation, and thus ameliorates AD development. Results To validate pathological activities in in vivo, we examined of the inhibitory effect of bvPLA2 on memory loss and tau phosphorylation as well as neuroinflammation by subcutaneous injection of bvPLA2 (0.5 mg/kg) to Tg2576 mice. For in vitro study, we examined the effect of bvPLA2 on cell death, tau pathology and neuroinflammation by treatment of bvPLA2 in LPS-activated PC12 cells. Our study showed that bvPLA2 mitigated memory impairment and spatial memory in Tg2576 mice, Agreed with the memory improvement, tau level and phosphorylation of tau were decreased by bvPLA2 treatment. Expression level of pro-inflammatory cytokines and inflammation-related proteins were also decreased in the brain of bvPLA2-treated Tg2576 mice. Conclusions Consideration of reduced tau level and phosphorylation of tau, GSK3β phosphorylation was studied. Phosphorylated GSK3β on Ser9 was significantly increased by treatment of bvPLA2, but a phosphorylated GSK3β on Tyr216 was significantly decreased in the Tg2576 mice brains. These data thus indicate that bvPLA2 prevents memory impairment through reduction of tau phosphorylation.