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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
- Source :
- Drug Design, Development and Therapy
- Publication Year :
- 2016
- Publisher :
- Informa UK Limited, 2016.
-
Abstract
- Kuo-Hsuan Chang,1,* I-Cheng Chen,1,* Hsuan-Yuan Lin,2 Hsuan-Chiang Chen,2 Chih-Hsin Lin,1 Te-Hsien Lin,2 Yu-Ting Weng,1 Chih-Ying Chao,1 Yih-Ru Wu,1 Jung-Yaw Lin,2 Guey-Jen Lee-Chen,2 Chiung-Mei Chen1 1Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 2Department of Life Science, National Taiwan Normal University, Taipei, Taiwan, Republic of China *These authors contributed equally to this work Background: 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.Materials and methods: Tau protein was coupled to the DsRed fluorophore by fusing a pro-aggregation mutant of repeat domain of tau (ΔK280 tauRD) with DsRed. The ΔK280 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.Results: Seven TCM extracts demonstrated a significant reduction in tau misfolding and reactive oxidative species with low cytotoxicity in the ΔK280 tauRD-DsRed 293 cell model. Glycyrrhiza inflata and Panax ginseng also demonstrated the potential to improve neurite outgrowth in the ΔK280 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 ΔK280 tauRD-DsRed 293 cells.Conclusion: 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. Keywords: Alzheimer’s disease, tauopathy, tau misfolding, TCM extracts, G. inflata, UPR-mediated chaperones
- Subjects :
- 0301 basic medicine
Pharmaceutical Science
tau misfolding
G. inflata
0302 clinical medicine
Drug Discovery
Medicine, Chinese Traditional
Original Research
Neurons
biology
Chemistry
Up-Regulation
Cell biology
Biochemistry
Tauopathy
Alzheimer's disease
Alzheimer’s disease
Glycyrrhiza inflata
UPR-mediated chaperones
Tau protein
tau Proteins
macromolecular substances
Models, Biological
Structure-Activity Relationship
03 medical and health sciences
Downregulation and upregulation
Alzheimer Disease
Cell Line, Tumor
Glycyrrhiza
medicine
Humans
Cell Proliferation
Protein Unfolding
Pharmacology
Drug Design, Development and Therapy
Dose-Response Relationship, Drug
Plant Extracts
Cell growth
tauopathy
HEK 293 cells
Water
biology.organism_classification
medicine.disease
HEK293 Cells
030104 developmental biology
Unfolded Protein Response
Unfolded protein response
biology.protein
TCM extracts
030217 neurology & neurosurgery
Drugs, Chinese Herbal
Molecular Chaperones
Subjects
Details
- ISSN :
- 11778881
- Database :
- OpenAIRE
- Journal :
- Drug Design, Development and Therapy
- Accession number :
- edsair.doi.dedup.....b38d3c1c5dca33175025e7d48367a341