ArticleProceedings of the National Academy of Sciences of the United States of America2012
Rational design of potent domain antibody inhibitors of amyloid fibril assembly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 105 citations in OpenAlex.
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- Peptide-based therapeutics in the management of Alzheimer's disease (AD) and their potential to develop novel strategies.Metabolic brain disease · 2026Review
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- Antimicrobial Peptides as Cross-Seeding Modulators at the Neurodegenerative-Infectious Interface.Research (Washington, D.C.) · 2026Review
- Revolutionizing Synthetic Antibody Design: Harnessing Artificial Intelligence and Deep Sequencing Big Data for Unprecedented Advances.Molecular biotechnology · 2025Review
- Article
- Single-domain antibodies and aptamers drive new opportunities for neurodegenerative disease research.Frontiers in immunology · 2024Review
- CNature communications · 2023Article
- Fragment-based computational design of antibodies targeting structured epitopes.Science advances · 2022Article
- Amphiphilic stilbene derivatives attenuate the neurotoxicity of soluble AβChemical science · 2022Article
- Substoichiometric Inhibition of Insulin against IAPP Aggregation Is Attenuated by the Incompletely Processed N-Terminus of proIAPP.ACS chemical neuroscience · 2022Article
- Destabilization of the Alzheimer's amyloid-β peptide by a proline-rich β-sheet breaker peptide: a molecular dynamics simulation study.Journal of molecular modeling · 2021Article
- Computational maturation of a single-domain antibody against Aβ42 aggregation.Chemical science · 2021Article
- Contribution of the Commensal Microflora to the Immunological Homeostasis and the Importance of Immune-Related Drug Development for Clinical Applications.International journal of molecular sciences · 2021Review
- Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review.Frontiers in pharmacology · 2021Review
- Visualizing and trapping transient oligomers in amyloid assembly pathways.Biophysical chemistry · 2021Review
- Peptide-Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy.International journal of molecular sciences · 2020Article
- A Luminescence-Based System for Identification of Genetically Encodable Inhibitors of Protein Aggregation.ACS omega · 2020Article
- Peptide-Based Molecular Strategies To Interfere with Protein Misfolding, Aggregation, and Cell Degeneration.Angewandte Chemie (International ed. in English) · 2020Review
- Single-Domain Antibodies as Therapeutic and Imaging Agents for the Treatment of CNS Diseases.Antibodies (Basel, Switzerland) · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Antibodies hold significant potential for inhibiting toxic protein aggregation associated with conformational disorders such as Alzheimer's and Huntington's diseases. However, near-stoichiometric antibody concentrations are typically required to completely inhibit protein aggregation. We posited that the molecular interactions mediating amyloid fibril formation could be harnessed to generate antibodies with potent antiaggregation. Here we report that grafting small amyloidogenic peptides (6-10 residues) into the complementarity-determining regions of a single-domain (V(H)) antibody yields potent domain antibody inhibitors of amyloid formation. Grafted AMyloid-Motif AntiBODIES (gammabodies) presenting hydrophobic peptides from Aβ (Alzheimer's disease), α-Synuclein (Parkinson's disease), and islet amyloid polypeptide (type 2 diabetes) inhibit fibril assembly of each corresponding polypeptide at low substoichiometric concentrations (1:10 gammabody:monomer molar ratio). In contrast, sequence- and conformation-specific antibodies that were obtained via immunization are unable to prevent fibrillization at the same substoichiometric concentrations. Gammabodies prevent amyloid formation by converting monomers and/or fibrillar intermediates into small complexes that are unstructured and benign. We expect that our antibody design approach--which eliminates the need for immunization or screening to identify sequence-specific domain antibody inhibitors--can be readily extended to generate potent aggregation inhibitors of other amyloidogenic polypeptides linked to human disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.