ArticleNature communications2024
The inhibitory action of the chaperone BRICHOS against the α-Synuclein secondary nucleation pathway.
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 15 papers.
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Who cites it
15 citing papers in PubMed.
- The emerging roles of ITM2A: At the molecular crossroads of development and pathogenesis.iScience · 2026Review
- Alpha-synuclein fibrils induce budding of mitochondrial-derived vesicles.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mechanism-selective inhibition of α-synuclein aggregation by the chaperone-like BRICHOS domain.The Journal of biological chemistry · 2026Article
- The amplification of α-synuclein amyloid fibrils.Biochemical Society transactions · 2026Review
- Differential effects of α-Synuclein monomers and seeds on the material properties of Tau condensates.bioRxiv : the preprint server for biology · 2026Article
- In vitro, cellular and in vivo studies of amyloid oligomers structure and toxicity: Challenges and advances.Protein science : a publication of the Protein Society · 2026Review
- Molecular Mechanisms of Islet Amyloid Polypeptide Aggregation: Towards Chemical Strategies to Prevent Amyloid Formation and to Design Non-Aggregating Peptide Therapeutics.International journal of molecular sciences · 2026Review
- Structural defects in amyloid-β fibrils drive secondary nucleation.Nature communications · 2026Article
- Phosphorylation of α‑Synuclein Fibrils at S129 Changes DNAJB1 Binding as Probed by Solid-State NMR.JACS Au · 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
- Mapping the Role of Monomer Conformation in the Amyloid Formation of α-Synuclein Splice Variants.Journal of the American Chemical Society · 2025Article
- Aducanumab Binding to AβbioRxiv : the preprint server for biology · 2025Article
- The Evolution of Functional Amyloids and Their Impact on Host-Microbe Interactions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Chaperone-Mediated Regulation of Tau Phase Separation, Fibrillation, and Toxicity.Journal of the American Chemical Society · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complex kinetics of disease-related amyloid aggregation of proteins such as α-Synuclein (α-Syn) in Parkinson's disease and Aβ42 in Alzheimer's disease include primary nucleation, amyloid fibril elongation and secondary nucleation. The latter can be a key accelerator of the aggregation process. It has been demonstrated that the chaperone domain BRICHOS can interfere with the secondary nucleation process of Aβ42. Here, we explore the mechanism of secondary nucleation inhibition of the BRICHOS domain of the lung surfactant protein (proSP-C) against α-Syn aggregation and amyloid formation. We determine the 3D NMR structure of an inactive trimer of proSP-C BRICHOS and its active monomer using a designed mutant. Furthermore, the interaction between the proSP-C BRICHOS chaperone and a substrate peptide has been studied. NMR-based interaction studies of proSP-C BRICHOS with α-Syn fibrils show that proSP-C BRICHOS binds to the C-terminal flexible fuzzy coat of the fibrils, which is the secondary nucleation site on the fibrils. Super-resolution fluorescence microscopy demonstrates that proSP-C BRICHOS runs along the fibrillar axis diffusion-dependently sweeping off monomeric α-Syn from the fibrils. The observed mechanism explains how a weakly binding chaperone can inhibit the α-Syn secondary nucleation pathway via avidity where a single proSP-C BRICHOS molecule is sufficient against up to ~7-40 α-Syn molecules embedded within the fibrils.
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