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 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.
Lin
Chih-Li
CL
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chen
Ta-Fu
TF
Chiu
Ming-Jang
MJ
Way
Tzong-Der
TD
Lin
Jen-Kun
JK
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*
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