title: Epigallocatechin gallate (EGCG) suppresses beta-amyloid-induced neurotoxicity through inhibiting c-Abl/FE65 nuclear translocation and GSK3 beta activation.
abstract: 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 tea 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 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 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 some mechanisms other than the promotion of APP nonamyloidogenic proteolysis, as was reported previously.
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Li
authors.initials: CL
authors.lastname: Lin
authors.forename: Ta-Fu
authors.initials: TF
authors.lastname: Chen
authors.forename: Ming-Jang
authors.initials: MJ
authors.lastname: Chiu
authors.forename: Tzong-Der
authors.initials: TD
authors.lastname: Way
authors.forename: Jen-Kun
authors.initials: JK
authors.lastname: Lin
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*
chemical_list: C091042:APBB1 protein, human; D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D002392:Catechin; C045651:epigallocatechin gallate; D016315:Proto-Oncogene Proteins c-abl; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3