ArticleProceedings of the National Academy of Sciences of the United States of America2014
Crucial role of nonspecific interactions in amyloid nucleation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
67 citing papers in PubMed, 193 citations in OpenAlex.
- Article
- Parkinson's disease-specific α-Synuclein variants potentially drive Lewy body formation by engaging in promiscuous and non-functional interactions.Communications biology · 2026Article
- Neurodegeneration Through the Lens of Bioinformatics Approaches: Computational Mechanisms of Protein Misfolding.International journal of molecular sciences · 2025Review
- Biomolecular condensates: molecular structure, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2025Review
- Molecular insights on the mechanism of α1-antitrypsin condensate formation and maturation.PLoS computational biology · 2025Article
- Charged peptides enriched in aromatic residues decelerate condensate ageing driven by cross-β-sheet formation.Nature communications · 2025Article
- Chemically Informed Coarse-Graining of Electrostatic Forces in Charge-Rich Biomolecular Condensates.ACS central science · 2025Article
- Multimer Detection System: A Universal Assay System for Differentiating Protein Oligomers from Monomers.International journal of molecular sciences · 2025Review
- Prediction and Evaluation of Protein Aggregation with Computational Methods.Methods in molecular biology (Clifton, N.J.) · 2025Review
- In silico analysis of fungal prion-like proteins for elucidating their role in plant-fungi interactions.Archives of microbiology · 2024Article
- Adding intrinsically disordered proteins to biological ageing clocks.Nature cell biology · 2024Review
- Genetic Algorithm for Automated Parameterization of Network Hamiltonian Models of Amyloid Fibril Formation.The journal of physical chemistry. B · 2024Article
- Self-replication of AProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Liquid-liquid phase separation driven by charge heterogeneity.Communications physics · 2024Article
- A Biomimetic Multiparametric Assay to Characterise Anti-Amyloid Drugs.International journal of molecular sciences · 2023Article
- Mapping the configurational landscape and aggregation phase behavior of the tau protein fragment PHF6.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Location and Concentration of Aromatic-Rich Segments Dictates the Percolating Inter-Molecular Network and Viscoelastic Properties of Ageing Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- A Hairpin Motif in the Amyloid-β Peptide Is Important for Formation of Disease-Related Oligomers.Journal of the American Chemical Society · 2023Article
- Amyloid Aggregation and Liquid-Liquid Phase Separation from the Perspective of Phase Transitions.The journal of physical chemistry. B · 2023Review
- Time-Dependent Material Properties of Aging Biomolecular Condensates from Different Viscoelasticity Measurements in Molecular Dynamics Simulations.The journal of physical chemistry. B · 2023Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protein oligomers have been implicated as toxic agents in a wide range of amyloid-related diseases. However, it has remained unsolved whether the oligomers are a necessary step in the formation of amyloid fibrils or just a dangerous byproduct. Analogously, it has not been resolved if the amyloid nucleation process is a classical one-step nucleation process or a two-step process involving prenucleation clusters. We use coarse-grained computer simulations to study the effect of nonspecific attractions between peptides on the primary nucleation process underlying amyloid fibrillization. We find that, for peptides that do not attract, the classical one-step nucleation mechanism is possible but only at nonphysiologically high peptide concentrations. At low peptide concentrations, which mimic the physiologically relevant regime, attractive interpeptide interactions are essential for fibril formation. Nucleation then inevitably takes place through a two-step mechanism involving prefibrillar oligomers. We show that oligomers not only help peptides meet each other but also, create an environment that facilitates the conversion of monomers into the β-sheet-rich form characteristic of fibrils. Nucleation typically does not proceed through the most prevalent oligomers but through an oligomer size that is only observed in rare fluctuations, which is why such aggregates might be hard to capture experimentally. Finally, we find that the nucleation of amyloid fibrils cannot be described by classical nucleation theory: in the two-step mechanism, the critical nucleus size increases with increases in both concentration and interpeptide interactions, which is in direct contrast with predictions from classical nucleation theory.
Indexed as
Identifiers
What OpenQuestion holds
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.