The Protective Effects Of IMM-H004 In AD-like Pathology Model Induced By Okadaic Acid

AimTo study the protective effect of coumarin derivative 004(IMM-H004)in OKA(okadaic Acid,OKA)-induced AD(Alzheimer disease,AD)-like neurotoxicity model.And to explore the mechanism of its neuroprotective effect based on Tau protein phosphorylation.MethodsMTT,LDH,flow cytometry,ROS and oxidative stress related kits were used to research the effect of 004;rats were injected with OKA to simulate the AD-like lesions,then were given different doses of 004.Morris water maze and Nissl were used to detect the spatial memory function and neuronal damage;the activity of PP2A was measured by Serine/Threonine Phosphatase Assay System;Western Blot and immunohistochemistry were used to study the mechanism of 004 primarily.ResultsOKA-treated cells showed significant apoptosis and rats showed spatial memory impairments,besides,both cells and rats presented significant phosphorylation of Tau.The results showed that 004 could inhibit apoptosis and oxidative stress injury of PC12 cells,and 004 repaired the damage of learning and memory of rats in hippocampus.Through the mechanism study we found 004 down-regulated the activity of protein kinases CDK5 and GSK3 ? and inhibited the phosphorylation of Tau protein.Conclusion004 can reverse apoptosis and oxidative damage induced by OKA of PC12 cells and hippocampal neuron apoptosis of rats,effectively attenuates spatial memory impairments and according to the results we know 004 inhibit Tau hyperphosphorylation by regulating PP2A,CDK5 and GSK3? both of cells and rats.