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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sigurdsson, Einar M. Kolodziej, Steven Friedland, Robert P. Hara, Mariko Sait, Hameetha B. R. O'nuallain, Brian Taguchi, Hiroaki Gonzalez, Veronica Paul, Sudhir Nishiyama, Yasuhiro Mitsuda, Yukie Planque, Stephanie A. Massey, Richard J. Lin, Yan Fukuchi, Ken-ichiro Sonoda, Sari |
| Description | Author Affiliation: Planque SA ( From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.); Nishiyama Y ( From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.); Sonoda S ( From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.); Lin Y ( the Departments of Neuroscience, Physiology, and Psychiatry, New York University School of Medicine, New York, New York 10016.); Taguchi H ( From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.); Hara M ( From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.); Kolodziej S ( From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.); Mitsuda Y ( From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.); Gonzalez V ( the Departments of Neuroscience, Physiology, and Psychiatry, New York University School of Medicine, New York, New York 10016.); Sait HB ( the Departments of Neuroscience, Physiology, and Psychiatry, New York University School of Medicine, New York, New York 10016.); Fukuchi K ( the Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, Illinois 61605.); Massey RJ ( Covalent Bioscience Inc., Houston, Texas 77054.); Friedland RP ( the Department of Neurology, University of Louisville School of Medicine, Louisville, Kentucky 40202, and.); O'Nuallain B ( the Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115.); Sigurdsson EM ( the Departments of Neuroscience, Physiology, and Psychiatry, New York University School of Medicine, New York, New York 10016, Einar.Sigurdsson@nyumc.org.); Paul S ( From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030, Sudhir.Paul@uth.tmc.edu.) |
| Abstract | 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 ß (Aß)-clearing effect of a catabody construct engineered from innate immunity principles. The catabody recognized the Aß C terminus noncovalently and hydrolyzed Aß rapidly, with no reactivity to the Aß precursor protein, transthyretin amyloid aggregates, or irrelevant proteins containing the catabody-sensitive Aß dipeptide unit. The catabody dissolved preformed Aß aggregates and inhibited Aß aggregation more potently than an Aß-binding IgG. Intravenous catabody treatment reduced brain Aß deposits in a mouse Alzheimer disease model without inducing microgliosis or microhemorrhages. Specific Aß hydrolysis appears to be an innate immune function that could be applied for therapeutic Aß removal. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 16 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-04-17 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Alzheimer Disease Metabolism Amyloid Beta-Peptides Antibodies, Catalytic Brain Single-Chain Antibodies Genetics Immunology Pathology Chemistry Animals Disease Models, Animal Gene Expression HEK293 Cells Hydrolysis Immunity, Innate Mice Peptide Fragments Protein Engineering Proteolysis Recombinant Proteins Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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