ArticleNature structural & molecular biology2015
A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers.
Article in Nature structural & molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 222 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
222 citing papers in PubMed, 417 citations in OpenAlex.
- From Helicobacter pylori CagA to Cross-Kingdom Amyloid Control: Emerging Anti-amyloid Biology, Mechanistic Paradoxes, and Translational Opportunities.The protein journal · 2026Review
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- Spontaneous aging of mature amyloids alters structural stability, cytotoxicity, and susceptibility to biological clearance.Cell death discovery · 2026Article
- Thermodynamic Frontiers in Hemoglobin-Inspired Polymer Science for Diagnosis and Modulation of Neurodegenerative Diseases.Cell biochemistry and function · 2026Review
- Mechanism-selective inhibition of α-synuclein aggregation by the chaperone-like BRICHOS domain.The Journal of biological chemistry · 2026Article
- The chaperone DNAJB6b halts amyloid formation through association with transient Aβ oligomers.Physical chemistry chemical physics : PCCP · 2026Article
- α/Sulfonyl-γ-AApeptide foldamers mitigate Alzheimer's disease pathology by stabilizing transient helical domains in Aβ.Nature communications · 2026Article
- The amplification of α-synuclein amyloid fibrils.Biochemical Society transactions · 2026Review
- Identification of Secondary Nucleation Inhibitors of Amyloid-β Aggregation by Cellular Selection of a SICLOPPS Library.Chembiochem : a European journal of chemical biology · 2026Article
- The temperature dependence of amyloidProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Decoding the mechanisms of amyloid-β in synaptic toxicity.Journal of Alzheimer's disease : JAD · 2026Review
- Structural defects in amyloid-β fibrils drive secondary nucleation.Nature communications · 2026Article
- Aducanumab binding to AβProceedings of the National Academy of Sciences of the United States of America · 2025Article
- A genetically encoded selection for amyloid-β oligomer binders.Nature chemical biology · 2025Article
- Modeling Protein Aggregation Kinetics from NMR Data.Journal of molecular biology · 2025Review
- Identification of a glia-associated amyloid β oligomer subtype and the rescue from reactive astrogliosis by inhibitor NU-9.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Structural reconstruction of individual filaments in AβCommunications chemistry · 2025Article
- From Pathology to Materials Science and Engineering: Harnessing the Amyloid State for Biotechnological Applications.ACS applied materials & interfaces · 2025Review
- Aducanumab Binding to AβbioRxiv : the preprint server for biology · 2025Article
- Evolving Data-Driven Strategies for the Characterization of Supramolecular Polymers and Systems.Angewandte Chemie (International ed. in English) · 2025Review
162 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Alzheimer's disease is an increasingly prevalent neurodegenerative disorder whose pathogenesis has been associated with aggregation of the amyloid-β peptide (Aβ42). Recent studies have revealed that once Aβ42 fibrils are generated, their surfaces effectively catalyze the formation of neurotoxic oligomers. Here we show that a molecular chaperone, a human Brichos domain, can specifically inhibit this catalytic cycle and limit human Aβ42 toxicity. We demonstrate in vitro that Brichos achieves this inhibition by binding to the surfaces of fibrils, thereby redirecting the aggregation reaction to a pathway that involves minimal formation of toxic oligomeric intermediates. We verify that this mechanism occurs in living mouse brain tissue by cytotoxicity and electrophysiology experiments. These results reveal that molecular chaperones can help maintain protein homeostasis by selectively suppressing critical microscopic steps within the complex reaction pathways responsible for the toxic effects of protein misfolding and aggregation.
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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.