Specific amyloid β clearance by a catalytic antibody construct
| Autor: | Yasuhiro Nishiyama, Einar M. Sigurdsson, Robert P. Friedland, Sari Sonoda, Yan Lin, Sudhir Paul, Brian O'Nuallain, Hiroaki Taguchi, Steven J. Kolodziej, Stephanie Planque, Mariko Hara, Hameetha B.R. Sait, Richard Massey, Veronica Gonzalez, Yukie Mitsuda, Ken Ichiro Fukuchi |
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| Rok vydání: | 2015 |
| Předmět: |
Amyloid
Proteolysis Immunology Gene Expression Antibodies Catalytic Protein Engineering Biochemistry Mice Alzheimer Disease medicine Animals Humans Molecular Biology Innate immune system Amyloid beta-Peptides medicine.diagnostic_test biology Chemistry Hydrolysis fungi Neurotoxicity P3 peptide food and beverages Brain Cell Biology medicine.disease Immunity Innate Peptide Fragments Recombinant Proteins Transthyretin Disease Models Animal HEK293 Cells biology.protein Antibody Alzheimer's disease Single-Chain Antibodies |
| Zdroj: | The Journal of biological chemistry. 290(16) |
| ISSN: | 1083-351X |
| Popis: | Classical immunization methods do not generate catalytic antibodies (catabodies), but recent findings suggest that the innate antibody repertoire is a rich catabody source. We describe the specificity and amyloid β (Aβ)-clearing effect of a catabody construct engineered from innate immunity principles. The catabody recognized the Aβ C terminus noncovalently and hydrolyzed Aβ rapidly, with no reactivity to the Aβ precursor protein, transthyretin amyloid aggregates, or irrelevant proteins containing the catabody-sensitive Aβ dipeptide unit. The catabody dissolved preformed Aβ aggregates and inhibited Aβ aggregation more potently than an Aβ-binding IgG. Intravenous catabody treatment reduced brain Aβ deposits in a mouse Alzheimer disease model without inducing microgliosis or microhemorrhages. Specific Aβ hydrolysis appears to be an innate immune function that could be applied for therapeutic Aβ removal. |
| Databáze: | OpenAIRE |
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