ArticleJournal of the American Chemical Society2023
A Hairpin Motif in the Amyloid-β Peptide Is Important for Formation of Disease-Related Oligomers.
Article in Journal of the American Chemical Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
- Hyphenated Mass Spectrometry-Based Strategies for Characterizing Oligomers of α‑Synuclein in Parkinson's Disease.ACS central science · 2026Article
- An N-terminal ATTR Fibril Segment Promotes Transthyretin Amyloid Nucleation and Polymorphism.bioRxiv : the preprint server for biology · 2026Article
- Membrane Complexity and Phase Behavior Dictate the Stability of Membrane-Inserted AβChemphyschem : a European journal of chemical physics and physical chemistry · 2026Article
- Targeting soluble misfolded oligomers in anti-amyloid research.Nature reviews. Chemistry · 2026Review
- Fine-Tuning hIAPP Amyloidogenesis: Probing Molecular Mechanisms via Fluorinated Core Substitutions.ACS bio & med chem Au · 2026Article
- Molecular Dynamics Simulations of AβACS omega · 2026Article
- Temperature-Dependent Dynamics of Aβ42 and α-Synuclein Monomers and Early Oligomerization of Aβ42: Shared Residues Mediate Intra- and Intermolecular β-Sheets.ACS chemical neuroscience · 2026Article
- The Monomeric Conformational Ensembles of Aβ40 and Aβ42 Encode Their Differential Amyloid Aggregation Propensity.The journal of physical chemistry. B · 2026Article
- Transient Aggregation-Prone States in Disordered Proteins as Therapeutic Targets: The Amyloid-β Case.Journal of chemical information and modeling · 2026Article
- A Rigid Supramolecular Solution to a Flexible Problem: A Multifunctional Calix[4]arene-Based Strategy to Prevent α‑Synuclein Toxicity.ACS central science · 2026Article
- Silver nanocubes-based plasmon-enhanced fluorescence for amplified detection and in situ tracking of amyloid-β aggregate.Mikrochimica acta · 2026Article
- Time-resolved solid-state nuclear magnetic resonance studies of amyloid-β oligomer formation.Methods in enzymology · 2026Review
- A lattice Monte Carlo model for amyloid fibril formation.Biophysics and physicobiology · 2026Article
- Energy Landscape and Kinetic Analysis of Molecular Dynamics Simulations for Intrinsically Disordered Proteins.The journal of physical chemistry. B · 2025Article
- Modulation of AβJournal of chemical information and modeling · 2025Article
- The Influence of POPC as a Coaggregate in Amyloid-β Oligomer Formation.ACS chemical neuroscience · 2025Article
- The role of hydrophobic collapse in cytotoxic and functional amyloid oligomerization.Biophysical journal · 2025Article
- Chameleonic Nature of Aβ: Implications for Alzheimer's and Other Amyloid Diseases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Exogenous prion-like proteins and their potential to trigger cognitive dysfunction.Molecular systems biology · 2025Article
- Multi-target approach to Alzheimer's disease prevention and treatment: antioxidant, anti-inflammatory, and amyloid- modulating mechanisms.Neurogenetics · 2025Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid-β (Aβ) peptide is associated with the development of Alzheimer's disease and is known to form highly neurotoxic prefibrillar oligomeric aggregates, which are difficult to study due to their transient, low-abundance, and heterogeneous nature. To obtain high-resolution information about oligomer structure and dynamics as well as relative populations of assembly states, we here employ a combination of native ion mobility mass spectrometry and molecular dynamics simulations. We find that the formation of Aβ oligomers is dependent on the presence of a specific β-hairpin motif in the peptide sequence. Oligomers initially grow spherically but start to form extended linear aggregates at oligomeric states larger than those of the tetramer. The population of the extended oligomers could be notably increased by introducing an intramolecular disulfide bond, which prearranges the peptide in the hairpin conformation, thereby promoting oligomeric structures but preventing conversion into mature fibrils. Conversely, truncating one of the β-strand-forming segments of Aβ decreased the hairpin propensity of the peptide and thus decreased the oligomer population, removed the formation of extended oligomers entirely, and decreased the aggregation propensity of the peptide. We thus propose that the observed extended oligomer state is related to the formation of an antiparallel sheet state, which then nucleates into the amyloid state. These studies provide increased mechanistic understanding of the earliest steps in Aβ aggregation and suggest that inhibition of Aβ folding into the hairpin conformation could be a viable strategy for reducing the amount of toxic oligomers.
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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 Socratic graph.