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Shuttling protein nucleolin is a microglia receptor for amyloid beta peptide 1-42.

Authors: Ozawa, D  Nakamura, T  Koike, M  Hirano, K  Miki, Y  Beppu, M 
Citation: Ozawa D, etal., Biol Pharm Bull. 2013;36(10):1587-93. Epub 2013 Aug 3.
Pubmed: (View Article at PubMed) PMID:23912744

Amyloid-beta peptide 1-42 (Abeta42) plays a key role in the neurotoxicity found in Alzheimer's disease. Mononuclear phagocytes in the brain (microglia), can potentially clear Abeta via phagocytosis. Recently, the shuttling-protein nucleolin has been shown to possess scavenger receptor-activity. Here, we investigated whether this receptor interacts specifically with Abeta type 1-42 and mediates its phagocytosis by microglia. While monomeric and fibril Abeta42 were phagocytosed by mouse microglial EOC2 cells, amyloid beta peptide 1-40 (Abeta40) was only weakly phagocytosed. Surface plasmon-resonance analysis revealed that nucleolin strongly associates with Abeta42, but only weakly associates with Abeta40. 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 Abeta42 by microglia. Additionally, nucleolin-transfected HEK293 cells phagocytosed monomeric and fibril Abeta42 but not monomeric and fibril Abeta40. Moreover, AGRO, a nucleolin-specific oligonucleotide aptamer, inhibited phagocytosis of monomeric and fibril Abeta42, but not monomeric and fibril Abeta40. These results indicate that nucleolin is a receptor that allows microglia to recognize monomeric and fibril Abeta42.


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CRRD Object Information
CRRD ID: 9686392
Created: 2015-02-05
Species: All species
Last Modified: 2015-02-05
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.