The Journal of biological chemistry, 2015-04, Vol.290 (16), p.10229-10241
2015
Details
- Autor(en) / Beteiligte
- Titel
- Specific Amyloid β Clearance by a Catalytic Antibody Construct
- Ist Teil von
- The Journal of biological chemistry, 2015-04, Vol.290 (16), p.10229-10241
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2015
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- 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. Background: Naturally occurring catalytic antibodies (catabodies) can hydrolyze peptide bonds. Results: A catabody engineered from innate immunity principles hydrolyzed amyloid β (Aβ) specifically, dissolved Aβ aggregates, and cleared brain Aβ deposits without evident toxicity. Conclusion: The catabody could potentially be developed as a therapy for Alzheimer disease. Significance: The innate catabody repertoire may be a source of useful catabodies to toxic amyloids.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9258eISSN: 1083-351XDOI: 10.1074/jbc.M115.641738Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4400338
- Format
- –
- Schlagworte
- Alzheimer Disease, Alzheimer Disease - genetics, Alzheimer Disease - immunology, Alzheimer Disease - metabolism, Alzheimer Disease - pathology, Amyloid beta-Peptides - chemistry, Amyloid beta-Peptides - metabolism, Amyloid-β (Abeta), Animals, Antibodies, Catalytic - chemistry, Antibodies, Catalytic - genetics, Antibodies, Catalytic - metabolism, Antibody Engineering, Brain - immunology, Brain - metabolism, Brain - pathology, Catalytic Antibodies, Disease Models, Animal, Enzyme Catalysis, Gene Expression, HEK293 Cells, Humans, Hydrolysis, Immunity, Innate, Immunology, Immunotherapy, Innate Immunity, Light Chain Variable Domain, Mice, Neurotoxicity, Peptide Fragments - chemistry, Protein Engineering, Proteolysis, Recombinant Proteins - chemistry, Recombinant Proteins - genetics, Recombinant Proteins - metabolism, Single-Chain Antibodies - chemistry, Single-Chain Antibodies - genetics, Single-Chain Antibodies - metabolism