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The aqueous extract of Glycyrrhiza inflata can upregulate unfolded protein response-mediated chaperones to reduce tau misfolding in cell models of Alzheimer's disease.


ABSTRACT: Alzheimer's disease (AD) and several neurodegenerative disorders known as tauopathies are characterized by misfolding and aggregation of tau protein. Although several studies have suggested the potential of traditional Chinese medicine (TCM) as treatment for neurodegenerative diseases, the role of TCM in treating AD and tauopathies have not been well explored.Tau protein was coupled to the DsRed fluorophore by fusing a pro-aggregation mutant of repeat domain of tau (?K280 tauRD) with DsRed. The ?K280 tauRD-DsRed fusion gene was then used to generate Tet-On 293 and SH-SY5Y cell clones as platforms to test the efficacy of 39 aqueous extracts of TCM in reducing tau misfolding and in neuroprotection.Seven TCM extracts demonstrated a significant reduction in tau misfolding and reactive oxidative species with low cytotoxicity in the ?K280 tauRD-DsRed 293 cell model. Glycyrrhiza inflata and Panax ginseng also demonstrated the potential to improve neurite outgrowth in the ?K280 tauRD-DsRed SH-SY5Y neuronal cell model. G. inflata further rescued the upregulation of ERN2 (pro-apoptotic) and downregulation of unfolded-protein-response-mediated chaperones ERP44, DNAJC3, and SERP1 in ?K280 tauRD-DsRed 293 cells.This in vitro study provides evidence that G. inflata may be a novel therapeutic for AD and tauopathies. Future applications of G. inflata on animal models of AD and tauopathies are warranted to corroborate its effect of reducing misfolding and potential disease modification.

SUBMITTER: Chang KH 

PROVIDER: S-EPMC4778784 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The aqueous extract of Glycyrrhiza inflata can upregulate unfolded protein response-mediated chaperones to reduce tau misfolding in cell models of Alzheimer's disease.

Chang Kuo-Hsuan KH   Chen I-Cheng IC   Lin Hsuan-Yuan HY   Chen Hsuan-Chiang HC   Lin Chih-Hsin CH   Lin Te-Hsien TH   Weng Yu-Ting YT   Chao Chih-Ying CY   Wu Yih-Ru YR   Lin Jung-Yaw JY   Lee-Chen Guey-Jen GJ   Chen Chiung-Mei CM  

Drug design, development and therapy 20160229


<h4>Background</h4>Alzheimer's disease (AD) and several neurodegenerative disorders known as tauopathies are characterized by misfolding and aggregation of tau protein. Although several studies have suggested the potential of traditional Chinese medicine (TCM) as treatment for neurodegenerative diseases, the role of TCM in treating AD and tauopathies have not been well explored.<h4>Materials and methods</h4>Tau protein was coupled to the DsRed fluorophore by fusing a pro-aggregation mutant of re  ...[more]

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