Epigallocatechin Gallate (Egcg) Suppresses Beta-Amyloid-Induced Neurotoxicity through Inhibiting C-Abl/Fe65 Nuclear Translocation and Gsk3 Beta Activation

Alzheimer's disease (AD) is the most common neurodegenerative disease and is caused by an accumulation of A beta plaque deposits in the brains. Evidence is increasing that green can flavonoids can protect cells from A beta-mediated neurotoxicity. However, the underlying mechanism remains Unclear. Here, We used a human neuronal cell line MC65 conditional expression of all amyloid precursor protein fragment (APP-C99) to investigate the protection mechanism of epigallocatechin gallate (EGCG), the main constituent of green tea. We demonstrated that treatment with EGCG reduced the A beta levels by enhancing endogenous APP nonamyloidogenic proteolytic processing. Furthermore, EGCG also decreased nuclear translocation of c- Abl and blocked APP-C99-dependent GSK3 beta activation, and these inhibitory effects occurred through the interruption of c-Abl/Fe65 interaction. Our results indicated that the neuroprotective action of EGCG may take place through sonic mechanisms other than the promotion of APP nonamyloidogenic proteolysis, as was reported previously