title: Copper enhances APP dimerization and promotes Aβ production.
abstract: Alzheimer's disease (AD) is characterized by the deposition of amyloid-β (Aβ) plaques, senile plaque. The Aβ peptide is cleaved from amyloid precursor protein (APP) by β-secretase and γ-secretase. Until now, many literatures have documented that the high concentration of copper is present in Aβ plaques and enhances aggregation of. The APP copper binding domain (CuBD) is located in the N-terminal next to the growth factor-like domain that gets involved in APP homodimerization. Importantly, dimerization of APP has profound effect on Aβ production. We investigated whether copper alters the state of APP dimerization and how it affects APP metabolism. Here, we demonstrate that copper enhanced APP dimerization and increased extracellular release of Aβ. Moreover, copper chelator, D-penicillamine, suppressed APP dimerization and decreased extracellular release of Aβ. These results suggest that the action of copper may be profoundly associated with the pathway of Aβ production in AD pathogenesis.
authors.affiliation: Department of Health Science, Kyoto University Graduate School of Medicine, 53 Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yasuha
authors.initials: Y
authors.lastname: Noda
authors.forename: Megumi
authors.initials: M
authors.lastname: Asada
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kubota
authors.forename: Masato
authors.initials: M
authors.lastname: Maesako
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Watanabe
authors.forename: Maiko
authors.initials: M
authors.lastname: Uemura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kihara
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Ayae
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Kengo
authors.initials: K
authors.lastname: Uemura
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D015153:Blotting, Western; D003300:Copper / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D055503:Protein Multimerization
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003300:Copper