ArticleProceedings of the National Academy of Sciences of the United States of America2021
All-or-none amyloid disassembly via chaperone-triggered fibril unzipping favors clearance of α-synuclein toxic species.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Fragmentation-Induced Disassembly and Reaggregation of α-Synuclein Amyloid Fibrils.ACS chemical neuroscience · 2026Article
- Zooming into Disease at the Nanoscale: High-Speed Atomic Force Microscopy in Biomedical Discovery.ACS nano · 2026Review
- Single-Molecule Techniques for Probing the Conformation, Dynamics and Interactions of Intrinsically Disordered Proteins.Biophysics reviews · 2025Article
- Structural polymorphism of α-synuclein fibrils alters the pathway of Hsc70-mediated disaggregation.The EMBO journal · 2025Article
- Nanoscale Analysis beyond Imaging by Atomic Force Microscopy: Molecular Perspectives on Oncology and Neurodegeneration.Small science · 2025Review
- DnaJB1 chaperone inhibits tau aggregation by recognizing its N-terminus.bioRxiv : the preprint server for biology · 2025Article
- Competing chaperone pathways in α-synuclein disaggregation and aggregation dynamics.Protein science : a publication of the Protein Society · 2025Article
- Article
- A single fibril study reveals that ApoE inhibits the elongation of Aβ42 fibrils in an isoform-dependent manner.Communications chemistry · 2025Article
- Stepwise recruitment of chaperone Hsc70 by DNAJB1 produces ordered arrays primed for bursts of amyloid fibril disassembly.Communications biology · 2025Article
- Exposed Hsp70-binding site impacts yeast Sup35 prion disaggregation and propagation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structure of cytotoxic amyloid oligomers generated during disaggregation.Journal of biochemistry · 2024Review
- A Targetable N-Terminal Motif Orchestrates α-Synuclein Oligomer-to-Fibril Conversion.Journal of the American Chemical Society · 2024Article
- Thermodynamic characterization of amyloid polymorphism by microfluidic transient incomplete separation.Chemical science · 2024Article
- Cooperative amyloid fibre binding and disassembly by the Hsp70 disaggregase.The EMBO journal · 2022Article
- A sudden collapse: the disaggregation of amyloid fibres.The EMBO journal · 2022Article
- Identification of a HTT-specific binding motif in DNAJB1 essential for suppression and disaggregation of HTT.Nature communications · 2022Article
- α-Synuclein Conformational Plasticity: Physiologic States, Pathologic Strains, and Biotechnological Applications.Biomolecules · 2022Review
- Molecular mechanisms of amyloid formation in living systems.Chemical science · 2022Review
- The yeast molecular chaperone, Hsp104, influences transthyretin aggregate formation.Frontiers in molecular neuroscience · 2022Article
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α-synuclein aggregation is present in Parkinson's disease and other neuropathologies. Among the assemblies that populate the amyloid formation process, oligomers and short fibrils are the most cytotoxic. The human Hsc70-based disaggregase system can resolve α-synuclein fibrils, but its ability to target other toxic assemblies has not been studied. Here, we show that this chaperone system preferentially disaggregates toxic oligomers and short fibrils, while its activity against large, less toxic amyloids is severely impaired. Biochemical and kinetic characterization of the disassembly process reveals that this behavior is the result of an all-or-none abrupt solubilization of individual aggregates. High-speed atomic force microscopy explicitly shows that disassembly starts with the destabilization of the tips and rapidly progresses to completion through protofilament unzipping and depolymerization without accumulation of harmful oligomeric intermediates. Our data provide molecular insights into the selective processing of toxic amyloids, which is critical to identify potential therapeutic targets against increasingly prevalent neurodegenerative disorders.
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