ArticleProceedings of the National Academy of Sciences of the United States of America2015
Zinc as chaperone-mimicking agent for retardation of amyloid β peptide fibril formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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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.
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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.
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Who cites it
56 citing papers in PubMed, 118 citations in OpenAlex.
- Glucagon-Like Peptide-1 Receptor Agonists Inhibit the Initiation of Toxic Amyloid-β42 Aggregation.Journal of the American Chemical Society · 2026Article
- The Impact of Zinc on Cellular Dynamics, Brain Function, and its Therapeutic Potential in Neuronal Regeneration.Molecular neurobiology · 2026Review
- Constant pH Molecular Dynamics Simulation of pH Effects on Amyloid-β Structure, Dynamics, and Metal-Binding.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Molecular interactions, structural effects, and binding affinities between silver ions (AgScientific reports · 2025Article
- A Relationship between the Structures and Neurotoxic Effects of Aβ Oligomers Stabilized by Different Metal Ions.ACS chemical neuroscience · 2024Article
- Extracellular Vesicles Slow Down Aβ(1-42) Aggregation by Interfering with the Amyloid Fibril Elongation Step.ACS chemical neuroscience · 2024Article
- The thermodynamics of neurodegenerative disease.Biophysics reviews · 2024Review
- Article
- Article
- Metal Binding of Alzheimer's Amyloid-β and Its Effect on Peptide Self-Assembly.Accounts of chemical research · 2023Article
- Short hydrophobic loop motifs in BRICHOS domains determine chaperone activity against amorphous protein aggregation but not against amyloid formation.Communications biology · 2023Article
- Current understanding of metal-dependent amyloid-β aggregation and toxicity.RSC chemical biology · 2023Review
- Multivariate effects of pH, salt, and ZnCommunications chemistry · 2022Article
- Effects of zinc and carnosine on aggregation kinetics of Amyloid-β40 peptide.Biochemistry and biophysics reports · 2022Article
- Article
- Molecular Mechanisms of Inhibition of Protein Amyloid Fibril Formation: Evidence and Perspectives Based on Kinetic Models.International journal of molecular sciences · 2022Review
- Repression Effects of Hydrolysates from Hen-Egg Proteins on Amyloid Fibril Formation.The journal of poultry science · 2022Article
- Neglected N-Truncated Amyloid-β Peptide and Its Mixed Cu-Zn Complexes.The protein journal · 2022Review
- Brain-derived neurotrophic factor in Alzheimer's disease and its pharmaceutical potential.Translational neurodegeneration · 2022Review
- Mechanistic Models of Protein Aggregation Across Length-Scales and Time-Scales: From the Test Tube to Neurodegenerative Disease.Frontiers in neuroscience · 2022Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metal ions have emerged to play a key role in the aggregation process of amyloid β (Aβ) peptide that is closely related to the pathogenesis of Alzheimer's disease. A detailed understanding of the underlying mechanistic process of peptide-metal interactions, however, has been challenging to obtain. By applying a combination of NMR relaxation dispersion and fluorescence kinetics methods we have investigated quantitatively the thermodynamic Aβ-Zn(2+) binding features as well as how Zn(2+) modulates the nucleation mechanism of the aggregation process. Our results show that, under near-physiological conditions, substoichiometric amounts of Zn(2+) effectively retard the generation of amyloid fibrils. A global kinetic profile analysis reveals that in the absence of zinc Aβ40 aggregation is driven by a monomer-dependent secondary nucleation process in addition to fibril-end elongation. In the presence of Zn(2+), the elongation rate is reduced, resulting in reduction of the aggregation rate, but not a complete inhibition of amyloid formation. We show that Zn(2+) transiently binds to residues in the N terminus of the monomeric peptide. A thermodynamic analysis supports a model where the N terminus is folded around the Zn(2+) ion, forming a marginally stable, short-lived folded Aβ40 species. This conformation is highly dynamic and only a few percent of the peptide molecules adopt this structure at any given time point. Our findings suggest that the folded Aβ40-Zn(2+) complex modulates the fibril ends, where elongation takes place, which efficiently retards fibril formation. In this conceptual framework we propose that zinc adopts the role of a minimal antiaggregation chaperone for Aβ40.
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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.