The Molecular Mechanism Of Curcumin On Neuroprotective Effect Via Inducing Autophagy In APPswe/PS1Double Transgenic Mice

Objectives：The main pathologic change of Alzheimer’s disease (AD)is the aggregation of beta-amyloid. Curcumin has been reported to preventand treat AD via restraining beta-amyloid in APPswe/PS1doubletransgenic mice,while the mechanisms are not fully understood. The studyaims to observe the effects of curcumin on the macroautophagy andbeta-amyloid expression in the APPswe/PS1double transgenic mice andinvestigate the potential molecular mechanism.Methods：Thirty APPswe/PS1double transgenic mice were enrolledin the study and randomly divided into three3groups: the control group(without curcumin), the low curcumin group (100ppm) and the highcurcumin group (500ppm). All the mice were regularly fed with curcuminfor six months. After sacrifice, the brains were immediately removed andfixed in the different fluids according to the request of the study.Immunohistochemistry (IHC) was applied to evaluate the expression ofAbeta and Beclin1. Immunofluorescence (IF) was used to observe the expression of microtube associated protein-2(MAP-2) and LC3Ⅰ/Ⅱ.Electron microscope was used to observe autophagy vacuoles. The effectsof curcumin on the expressions of PI3K, Akt (total Akt and p-Akt), mTOR(total mTOR and p-mTOR), LC3Ⅰ/Ⅱ and Beclin were detected real-timePCR and Western blot.Results：The Morris Maze test showed that curcumin could improvethe impaired reference and spatial memory in the APPswe/PS1doubletransgenic mice. Electron microscope showed that the autophagy vacuoleswere increased after curcumin treatment. IHC showed that curcumindecreased the aggregation of Abeta and Beclin. Curcumin increased theexpression of MAP-2and LC3Ⅰ/Ⅱ. Real-time PCR and Western blotresults showed that curcumin decreased the activity of PI3K/Akt andmTOR.Conclusion：Curcumin play an important role in neuroprotectioneffect on Alzheimer’s disease (AD). Curcumin increases macroautophagyvia PI3K/Akt/mTOR pathway and promotes the clearance of Abeta, andinduces the autophagy axonal transport Taken together, all the resultsprovide a new target for AD treatment by curcumin.