Dihydrotanshinone I Increase Amyloid-β Clearance and Decrease Tau Phosphorylation via Enhancing Autophagy
- 20 March 2020
- journal article
- research article
- Published by S. Karger AG in Pharmacology
- Vol. 105 (5-6), 311-319
- https://doi.org/10.1159/000503792
Abstract
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
This publication has 24 references indexed in Scilit:
- Rapamycin Attenuates the Progression of Tau Pathology in P301S Tau Transgenic MicePLOS ONE, 2013
- Alzheimer Mechanisms and Therapeutic StrategiesCell, 2012
- Genes Involved in Cerebrospinal Fluid Production as Candidate Genes for Late-Onset Alzheimer's Disease: A HypothesisJournal of Neurogenetics, 2011
- A small‐molecule enhancer of autophagy decreases levels of Aβ and APP‐CTF via Atg5‐dependent autophagy pathway The FASEB Journal, 2011
- AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1Nature, 2011
- Novel synthetic small‐molecule activators of AMPK as enhancers of autophagy and amyloid‐β peptide degradationThe FASEB Journal, 2010
- Ulk1 plays a critical role in the autophagic clearance of mitochondria and ribosomes during reticulocyte maturationBlood, 2008
- Autophagy fights disease through cellular self-digestionNature, 2008
- Small molecule regulators of autophagy identified by an image-based high-throughput screenProceedings of the National Academy of Sciences of the United States of America, 2007
- The role of autophagy during the early neonatal starvation periodNature, 2004