ArticleProceedings of the National Academy of Sciences of the United States of America2005
Structural properties of Abeta protofibrils stabilized by a small molecule.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- The cellular model for Alzheimer's disease research: PC12 cells.Frontiers in molecular neuroscience · 2022Pooled it
- Safety, tolerability and immunogenicity of vaccine ALZ-101 in patients with early Alzheimer's disease: randomised, controlled trial.Alzheimer's research & therapy · 2026Trial
- Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.Molecular neurodegeneration · 2024Review
- Early events in amyloid-β self-assembly probed by time-resolved solid state NMR and light scattering.Nature communications · 2023Article
- Unveiling the Potential of Polyphenols as Anti-Amyloid Molecules in Alzheimer's Disease.Current neuropharmacology · 2023Review
- A Brain-Targeting Bispecific-Multivalent Antibody Clears Soluble Amyloid-Beta Aggregates in Alzheimer's Disease Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Constraints on the Structure of Fibrils Formed by a Racemic Mixture of Amyloid-β Peptides from Solid-State NMR, Electron Microscopy, and Theory.Journal of the American Chemical Society · 2021Article
- Protein Footprinting via Covalent Protein Painting Reveals Structural Changes of the Proteome in Alzheimer's Disease.Journal of proteome research · 2021Article
- Tau Inclusions in Alzheimer's, Chronic Traumatic Encephalopathy and Pick's Disease. A Speculation on How Differences in Backbone Polarization Underlie Divergent Pathways of Tau Aggregation.Frontiers in neuroscience · 2019Article
- Depletion of amyloid-β peptides from solution by sequestration within fibril-seeded hydrogels.Protein science : a publication of the Protein Society · 2018Article
- HIV Tat protein and amyloid-β peptide form multifibrillar structures that cause neurotoxicity.Nature structural & molecular biology · 2017Article
- Protein folding, misfolding and aggregation: The importance of two-electron stabilizing interactions.PloS one · 2017Article
- Rapid α-oligomer formation mediated by the Aβ C terminus initiates an amyloid assembly pathway.Nature communications · 2016Article
- Molecular Structure of Aggregated Amyloid-β: Insights from Solid-State Nuclear Magnetic Resonance.Cold Spring Harbor perspectives in medicine · 2016Review
- C-Terminal Threonine Reduces Aβ43 Amyloidogenicity Compared with Aβ42.Journal of molecular biology · 2016Article
- Successive Stages of Amyloid-β Self-Assembly Characterized by Solid-State Nuclear Magnetic Resonance with Dynamic Nuclear Polarization.Journal of the American Chemical Society · 2015Article
- Review
- Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta.eLife · 2013Article
- Molecular structures of amyloid and prion fibrils: consensus versus controversy.Accounts of chemical research · 2013Review
- Halogenation generates effective modulators of amyloid-Beta aggregation and neurotoxicity.PloS one · 2013Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Metastable oligomeric and protofibrillar forms of amyloidogenic proteins have been implicated as on-pathway assembly intermediates in amyloid formation and as the major toxic species in a number of amyloid diseases including Alzheimer's disease. We describe here a chemical biology approach to structural analysis of Abeta protofibrils. Library screening yielded several molecules that stimulate Abeta aggregation. One of these compounds, calmidazolium chloride (CLC), rapidly and efficiently converts Abeta(1-40) monomers into clusters of protofibrils. As monitored by electron microscopy, these protofibrils persist for days when incubated in PBS at 37 degrees C, with a slow transition to fibrillar structures apparent only after several weeks. Like normal protofibrils, the CLC-Abeta aggregates exhibit a low thioflavin T response. Like Abeta fibrils, the clustered protofibrils bind the anti-amyloid Ab WO1. The CLC-Abeta aggregates exhibit the same protection from hydrogen-deuterium exchange as do protofibrils isolated from a spontaneous Abeta fibril formation reaction: approximately 12 of the 39 Abeta(1-40) backbone amide protons are protected from exchange in the protofibril, compared with approximately twice that number in amyloid fibrils. Scanning proline mutagenesis analysis shows that the Abeta molecule in these protofibrillar assemblies exhibits the same flexible N and C termini as do mature amyloid fibrils. The major difference in Abeta conformation between fibrils and protofibrils is added structural definition in the 22-29 segment in the fibril. Besides aiding structural analysis, compounds capable of facilitating oligomer and protofibril formation might have therapeutic potential, if they act to sequester Abeta in a form and/or location that cannot engage the toxic pathway.
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