Academic Journal
Multimerization of a rationally designed nanobody for enhanced avidity toward Aβ42 oligomers.
| Τίτλος: | Multimerization of a rationally designed nanobody for enhanced avidity toward Aβ42 oligomers. |
|---|---|
| Συγγραφείς: | Nowinska M; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK., Suh E; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK., Mogilevsky C; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK., Vendruscolo M; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK. |
| Πηγή: | Protein science : a publication of the Protein Society [Protein Sci] 2026 Sep; Vol. 35 (9), pp. e70754. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9211750 Publication Model: Print Cited Medium: Internet ISSN: 1469-896X (Electronic) Linking ISSN: 09618368 NLM ISO Abbreviation: Protein Sci Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2001- : Woodbury, NY : Cold Spring Harbor Laboratory Press Original Publication: New York, N.Y. : Cambridge University Press, c1992- |
| Ιατρικοί όροι (MeSH): | Amyloid beta-Peptides*/chemistry , Amyloid beta-Peptides*/immunology , Amyloid beta-Peptides*/metabolism , Peptide Fragments*/chemistry , Peptide Fragments*/immunology , Peptide Fragments*/metabolism , Single-Domain Antibodies*/chemistry , Single-Domain Antibodies*/genetics , Single-Domain Antibodies*/immunology , Protein Multimerization*, Humans ; Alzheimer Disease |
| Περίληψη: | Alzheimer's disease affects tens of millions of people worldwide and is associated with the self-assembly of the Aβ42 peptide into amyloid aggregates. Among the species formed during this process, soluble oligomeric intermediates are the most closely linked to neurotoxicity and are therefore an attractive target for both therapeutic and diagnostic strategies. Their conformational heterogeneity and transient nature, however, have so far hindered the development of reagents that recognize them selectively, and no fully quantitative biomarker of Aβ42 oligomers is widely available. To address this problem, we use a rationally designed conformation-specific single-domain antibody, DesAbO, which binds selectively to Aβ42 oligomers. By using enzyme-linked immunosorbent assay, we show that encoding self-assembling multimerization domains in the DesAbO plasmid yields multimeric variants with increased avidity toward Aβ42 oligomers. In aggregation assays, the multimeric variants inhibited Aβ42 aggregation at concentrations at which the monomeric form was no longer effective, with the SB175 trimer performing best. These results show how multimerization can be used to enhance the recognition of Aβ42 oligomers and offer a route toward diagnostic and therapeutic agents for Alzheimer's disease and other protein misfolding disorders. (© 2026 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.) |
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| Grant Information: | 10059436 UK Research and Innovation; 10061100 UK Research and Innovation |
| Contributed Indexing: | Keywords: Alzheimer’s disease; Aβ42 oligomers; avidity; multivalency; nanobodies; protein aggregation |
| Substance Nomenclature: | 0 (Amyloid beta-Peptides) 0 (Peptide Fragments) 0 (amyloid beta-protein (1-42)) 0 (Single-Domain Antibodies) |
| Entry Date(s): | Date Created: 20260819 Date Completed: 20260819 Latest Revision: 20260926 |
| Update Code: | 20260926 |
| PubMed Central ID: | PMC13488367 |
| DOI: | 10.1002/pro.70754 |
| PMID: | 42615560 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1469-896X |
|---|---|
| DOI: | 10.1002/pro.70754 |