Epigallocatechin gallate (EGCG) suppresses β-amyloid-induced neurotoxicity through inhibiting c-Abl/FE65 nuclear translocation and GSK3β activation

Alzheimer's disease (AD) is the most common neurodegenerative disease and is caused by an accumulation of Aβ plaque deposits in the brains. Evidence is increasing that green tea flavonoids can protect cells from Aβ-mediated neurotoxicity. However, the underlying mechanism remains unclear. Here, we used a human neuronal cell line MC65 conditional expression of an 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 Aβ levels by enhancing endogenous APP nonamyloidogenic proteolytic processing. Furthermore, EGCG also decreased nuclear translocation of c-Abl and blocked APP-C99-dependent GSK3β 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 some mechanisms other than the promotion of APP nonamyloidogenic proteolysis, as was reported previously.