Epigallocatechin-3-gallate and curcumin suppress amyloid beta-induced beta-site APP cleaving enzyme-1 upregulation.
Beta-site APP cleaving enzyme-1 (BACE-1), is a rate-limiting enzyme for beta amyloid production. Beta amyloid induces the production of radical oxygen species and neuronal injury. Oxidative stress plays a key role in various neurological diseases such as ischemia and Alzheimer's disease. Recent studies suggest that oxidative stress induces BACE-1 protein upregulation in neuronal cells. Here, we demonstrate that naturally occurring compounds (-)-epigallocatechin-3-gallate and curcumin suppress beta amyloid-induced BACE-1 upregulation. Exposure of beta amyloid 1-42 to neuronal culture increased BACE-1 protein levels. (-)-Epigallocatechin-3-gallate or curcumin significantly attenuated beta amyloid-induced radical oxygen species production and beta-sheet structure formation. These two compounds have novel pharmacological effects that may be beneficial for Alzheimer's disease treatment.
Shimmyo
Yoshiari
Y
Department of Neuroscience for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. hsugimot@pharm.kyoto-u.ac.jp
Kihara
Takeshi
T
Akaike
Akinori
A
Niidome
Tetsuhiro
T
Sugimoto
Hachiro
H
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D002392:Catechin; C045651:epigallocatechin gallate; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D003474:Curcumin