title: Shuttling protein nucleolin is a microglia receptor for amyloid beta peptide 1-42.
abstract: Amyloid-beta peptide 1-42 (Aβ42) plays a key role in the neurotoxicity found in Alzheimer's disease. Mononuclear phagocytes in the brain (microglia), can potentially clear Aβ via phagocytosis. Recently, the shuttling-protein nucleolin has been shown to possess scavenger receptor-activity. Here, we investigated whether this receptor interacts specifically with Aβ type 1-42 and mediates its phagocytosis by microglia. While monomeric and fibril Aβ42 were phagocytosed by mouse microglial EOC2 cells, amyloid β peptide 1-40 (Aβ40) was only weakly phagocytosed. Surface plasmon-resonance analysis revealed that nucleolin strongly associates with Aβ42, but only weakly associates with Aβ40. Immunofluorescence staining of anti-nucleolin antibody revealed that EOC2 cells and rat primary microglia express nucleolin on their cell surfaces. Further, pretreating EOC2 cells with anti-nucleolin antibody, but not immunoglobulin G (IgG), inhibited phagocytosis of monomeric Aβ42 by microglia. Additionally, nucleolin-transfected HEK293 cells phagocytosed monomeric and fibril Aβ42 but not monomeric and fibril Aβ40. Moreover, AGRO, a nucleolin-specific oligonucleotide aptamer, inhibited phagocytosis of monomeric and fibril Aβ42, but not monomeric and fibril Aβ40. These results indicate that nucleolin is a receptor that allows microglia to recognize monomeric and fibril Aβ42.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ozawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masanori
authors.initials: M
authors.lastname: Koike
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hirano
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Miki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Beppu
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D012157:Mononuclear Phagocyte System; D010587:Phagocytosis; D010750:Phosphoproteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D000097796:Nucleolin
chemical_list: D016229:Amyloid beta-Peptides; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin