ArticleNature communications2024
Identification of potential aggregation hotspots on Aβ42 fibrils blocked by the anti-amyloid chaperone-like BRICHOS domain.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- BRICHOS-Biased Inhibition Contributes to Aβ42 Dominance in Parenchymal Plaques Despite Higher Aβ40 Abundance and Coaggregation Capability.Biomacromolecules · 2026Article
- Mechanism-selective inhibition of α-synuclein aggregation by the chaperone-like BRICHOS domain.The Journal of biological chemistry · 2026Article
- Glucagon-Like Peptide-1 Receptor Agonists Inhibit the Initiation of Toxic Amyloid-β42 Aggregation.Journal of the American Chemical Society · 2026Article
- Structural defects in amyloid-β fibrils drive secondary nucleation.Nature communications · 2026Article
- Heterogeneous Dynamics of the Fuzzy Coat of Full-Length Phospho-Mimetic Tau Fibrils.Journal of the American Chemical Society · 2026Article
- Aducanumab binding to AβProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cross-seeding of IAPP and Aβ42: A review of the molecular link between type 2 diabetes and Alzheimer's disease.Metabolic brain disease · 2025Review
- Orexin-A and Circadian Disruption in Alzheimer's Disease: Implications for Amyloid-Beta Pathology.Molecular neurobiology · 2025Article
- A genetically encoded selection for amyloid-β oligomer binders.Nature chemical biology · 2025Article
- Aducanumab Binding to AβbioRxiv : the preprint server for biology · 2025Article
- Chaperone-Mediated Regulation of Tau Phase Separation, Fibrillation, and Toxicity.Journal of the American Chemical Society · 2025Article
- Inducers and modulators of protein aggregation in Alzheimer's disease - Critical tools for understanding the foundations of aggregate structures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Determinants for Substoichiometric Inhibition of IAPP and Aβ Amyloid Aggregations by Bri2 BRICHOS.ACS chemical neuroscience · 2025Article
- Diversity of Aβ aggregates produced in a gut-based Drosophila model of Alzheimer's disease.PloS one · 2025Article
- Intravenous chaperone treatment of late-stage Alzheimer´s disease (AD) mouse model affects amyloid plaque load, reactive gliosis and AD-related genes.Translational psychiatry · 2024Article
- Specific inhibition of α-synuclein oligomer generation and toxicity by the chaperone domain Bri2 BRICHOS.Protein science : a publication of the Protein Society · 2024Article
- Modulation of Alzheimer's Disease Aβ40 Fibril Polymorphism by the Small Heat Shock Protein αB-Crystallin.Journal of the American Chemical Society · 2024Article
- Molecular basis for different substrate-binding sites and chaperone functions of the BRICHOS domain.Protein science : a publication of the Protein Society · 2024Article
- The Ability of DNAJB6b to Suppress Amyloid Formation Depends on the Chaperone Aggregation State.ACS chemical neuroscience · 2024Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein misfolding can generate toxic intermediates, which underlies several devastating diseases, such as Alzheimer's disease (AD). The surface of AD-associated amyloid-β peptide (Aβ) fibrils has been suggested to act as a catalyzer for self-replication and generation of potentially toxic species. Specifically tailored molecular chaperones, such as the BRICHOS protein domain, were shown to bind to amyloid fibrils and break this autocatalytic cycle. Here, we identify a site on the Aβ42 fibril surface, consisting of three C-terminal β-strands and particularly the solvent-exposed β-strand stretching from residues 26-28, which is efficiently sensed by a designed variant of Bri2 BRICHOS. Remarkably, while only a low amount of BRICHOS binds to Aβ42 fibrils, fibril-catalyzed nucleation processes are effectively prevented, suggesting that the identified site acts as a catalytic aggregation hotspot, which can specifically be blocked by BRICHOS. Hence, these findings provide an understanding how toxic nucleation events can be targeted by molecular chaperones.
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