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 Chen 1
29 February 2016
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 (ΔK280 tau RD) with DsRed. The ΔK280 tau RD-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 ΔK280 tau RD-DsRed 293 cell model. Glycyrrhiza inflata and Panax ginseng also demonstrated the potential to improve neurite outgrowth in the ΔK280 tau RD-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 tau RD-DsRed 293 cells.