Introduction: The plaques formed by amyloid-β (Aβ) accumulation and neurofibrillary tangles formed by hyper-phosphorylated tau protein are the 2 major pathologies of Alzheimer’s disease (AD). Recently, autophagy is considered to be a self-degradation process of preserved cytoplasmic abnormal substances, including Aβ and tau. Methods: α-Screen assay is used to discover a new mammalian target of rapamycin (mTOR) signaling inhibitor, and laser scanning confocal microscopic analysis is used to investigate the autophagy formation. Lastly, ELISA and Western blot assays are used to identify the mTOR signaling inhibitor effect on Aβ and tau and the underlying mechanism. Results: In the current study, we discover that dihydrotanshinone I (DTS I), extracted from Radix Salviae, can obviously inhibit mTOR phosphorylation and increase autophagy via increasing AMPK phosphorylation. Further study demonstrates that DTS I increases Aβ clearance and decreases Tau phosphorylation through autophagy enhancement involved with AMPK/mTOR pathway. Conclusion: Our study indicates that DTS I can increase Aβ clearance and decrease Tau phosphorylation via autophagy enhancing involved with AMPK/mTOR pathway, which highlights the therapeutic potential of DTS I for the treatment of AD.

Keywords:
Alzheimer’s disease, Dihydrotanshinone I, Amyloid-β, Tau, Autophagy
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2020
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