ArticleNature communications2021
The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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Who cites it
48 citing papers in PubMed, 83 citations in OpenAlex.
- Microfluidic diffusional sizing in bioanalysis and biosensing.Lab on a chip · 2026Review
- Small bites for big problems: stepwise aggregate degradation by autophagy.Biochemical Society transactions · 2026Review
- Stress-specific expression of HSPA and DNAJ chaperones regulated by NRF2/HSF1 in neurodegenerative conditions.Molecular and cellular biochemistry · 2026Article
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- Thermodynamic stability modulates chaperone-mediated disaggregation of α-synuclein fibrils.Chemical science · 2026Article
- Intracellular aggregation of the transthyretin protein is limited by Hsp70 chaperones.bioRxiv : the preprint server for biology · 2025Article
- Cardiolipin and mitochondrial membrane integrity in neurodegeneration: insights from α-synuclein-driven Parkinson's disease.Acta neuropathologica communications · 2025Review
- Structural polymorphism of α-synuclein fibrils alters the pathway of Hsc70-mediated disaggregation.The EMBO journal · 2025Article
- A universal entropic pulling force caused by binding.Nature communications · 2025Article
- 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
- A chaperone-proteasome-based fragmentation machinery is essential for aggrephagy.Nature cell biology · 2025Article
- Microfluidics for protein interaction studies: current methods, challenges, and future perspectives.European biophysics journal : EBJ · 2025Review
- EGFR phosphorylates DNAJB1 to suppress α-synuclein aggregation in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Mechanism of ATP hydrolysis in the Hsp70 BiP nucleotide-binding domain.Nature communications · 2025Article
- Stepwise recruitment of chaperone Hsc70 by DNAJB1 produces ordered arrays primed for bursts of amyloid fibril disassembly.Communications biology · 2025Article
- Lipidic folding pathway of α-Synuclein via a toxic oligomer.Nature communications · 2025Article
- Article
- 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
- The inhibitory action of the chaperone BRICHOS against the α-Synuclein secondary nucleation pathway.Nature communications · 2024Article
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
Abstract
Molecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disaggregate otherwise irreversible aggregate species such as α-synuclein fibrils, which accumulate in Parkinson's disease. However, the mechanisms and kinetics of this key functionality are only partially understood. Here, we combine microfluidic measurements with chemical kinetics to study α-synuclein disaggregation. We show that Hsc70 together with its co-chaperones DnaJB1 and Apg2 can completely reverse α-synuclein aggregation back to its soluble monomeric state. This reaction proceeds through first-order kinetics where monomer units are removed directly from the fibril ends with little contribution from intermediate fibril fragmentation steps. These findings extend our mechanistic understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and inform on possibilities and limitations of this strategy in the development of therapeutics against synucleinopathies.
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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 OpenQuestion graph.