Epitopes described in "Autoantibody-catalyzed hydrolysis of amyloid beta peptide."

Article Authors:Hiroaki Taguchi; Stephanie Planque; Yasuhiro Nishiyama; Jindrich Symersky; Stephane Boivin; Paul Szabo; Robert P Friedland; Paul A Ramsland; Allen B Edmundson; Marc E Weksler; Sudhir Paul
Article Title:Autoantibody-catalyzed hydrolysis of amyloid beta peptide.
Reference Detail
Reference ID:1012458
Abstract:We describe IgM class human autoantibodies that hydrolyze amyloid beta peptide 1-40 (Abeta40). A monoclonal IgM from a patient with Waldenström's macroglobulinemia hydrolyzed Abeta40 at the Lys-28-Gly-29 bond and Lys-16-Ala-17 bonds. The catalytic activity was inhibited stoichiometrically by an electrophilic serine protease inhibitor. Treatment with the catalytic IgM blocked the aggregation and toxicity of Abeta40 in neuronal cell cultures. IgMs purified from the sera of patients with Alzheimer disease (AD) hydrolyzed Abeta40 at rates superior to IgMs from age-matched humans without dementia. IgMs from non-elderly humans expressed the least catalytic activity. The reaction rate was sufficient to afford appreciable degradation at physiological Abeta and IgM concentrations found in peripheral circulation. Increased Abeta concentrations in the AD brain are thought to induce neurodegenerative effects. Peripheral administration of Abeta binding antibodies has been suggested as a potential treatment of AD. Our results suggest that catalytic IgM autoantibodies can help clear Abeta, and they open the possibility of using catalytic Abs for AD immunotherapy.
Reference Type:Literature
PubMed ID:18086674
Journal:J Biol Chem
Journal Volume:283
Article Pages:4714-22
Journal ISSN:0021-9258
Article Chemical List:Amyloid beta-Peptides;Antibodies, Monoclonal;Autoantibodies;Immunoglobulin M;Peptide Fragments;Serine Proteinase Inhibitors;amyloid beta-protein (1-40)
Article MeSH List:Adult; Aged; Aged, 80 and over; Alzheimer Disease(blood; immunology; therapy); Amyloid beta-Peptides(chemistry; immunology; metabolism); Antibodies, Monoclonal(blood; chemistry; immunology); Autoantibodies(blood; chemistry; immunology); Brain(immunology; metabolism); Catalysis; Female; Humans; Hydrolysis; Immunoglobulin M(chemistry; immunology; metabolism); Immunotherapy; Male; Peptide Fragments(chemistry; immunology; metabolism); Serine Proteinase Inhibitors(chemistry); Waldenstrom Macroglobulinemia(blood; immunology; therapy)
Curation Last Updated:2015-07-24 20:08:53