ArticleProceedings of the National Academy of Sciences of the United States of America2012
Molecular mechanisms used by chaperones to reduce the toxicity of aberrant protein oligomers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 160 citations in OpenAlex.
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- The Importance of Being Imperfect: Structure and Function of Bacterial Amyloid.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- From Pathology to Materials Science and Engineering: Harnessing the Amyloid State for Biotechnological Applications.ACS applied materials & interfaces · 2025Review
- Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Article
- Aneuploidy-induced proteostasis disruption impairs mitochondrial functions and mediates aggregation of mitochondrial precursor proteins through SQSTM1/p62.Nature communications · 2025Article
- TARGETING SOLUBLE AMYLOID-BETA OLIGOMERS WITH A NOVEL NANOBODY.Research square · 2024Article
- Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.Molecular neurodegeneration · 2024Review
- Clusterin Binding Modulates the Aggregation and Neurotoxicity of Amyloid-β(1-42).Molecular neurobiology · 2022Article
- From Small Peptides to Large Proteins against Alzheimer'sDisease.Biomolecules · 2022Review
- Structural basis for the inhibition of IAPP fibril formation by the co-chaperonin prefoldin.Nature communications · 2022Article
- Chaperones mainly suppress primary nucleation during formation of functional amyloid required for bacterial biofilm formation.Chemical science · 2022Article
- The role of heat shock proteins in preventing amyloid toxicity.Frontiers in molecular biosciences · 2022Review
- Brain Cells Release Calreticulin That Attracts and Activates Microglia, and Inhibits Amyloid Beta Aggregation and Neurotoxicity.Frontiers in immunology · 2022Article
- Truncation-Driven Lateral Association of α-Synuclein Hinders Amyloid Clearance by the Hsp70-Based Disaggregase.International journal of molecular sciences · 2021Article
- Distinct responses of human peripheral blood cells to different misfolded protein oligomers.Immunology · 2021Article
- Quantitative Measurement of the Affinity of Toxic and Nontoxic Misfolded Protein Oligomers for Lipid Bilayers and of its Modulation by Lipid Composition and Trodusquemine.ACS chemical neuroscience · 2021Article
- Exogenous misfolded protein oligomers can cross the intestinal barrier and cause a disease phenotype in C. elegans.Scientific reports · 2021Article
- The release of toxic oligomers from α-synuclein fibrils induces dysfunction in neuronal cells.Nature communications · 2021Article
- Could Small Heat Shock Protein HSP27 Be a First-Line Target for Preventing Protein Aggregation in Parkinson's Disease?International journal of molecular sciences · 2021Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 6 countries.
Funding
Abstract
Chaperones are the primary regulators of the proteostasis network and are known to facilitate protein folding, inhibit protein aggregation, and promote disaggregation and clearance of misfolded aggregates inside cells. We have tested the effects of five chaperones on the toxicity of misfolded oligomers preformed from three different proteins added extracellularly to cultured cells. All the chaperones were found to decrease oligomer toxicity significantly, even at very low chaperone/protein molar ratios, provided that they were added extracellularly rather than being overexpressed in the cytosol. Infrared spectroscopy and site-directed labeling experiments using pyrene ruled out structural reorganizations within the discrete oligomers. Rather, confocal microscopy, SDS-PAGE, and intrinsic fluorescence measurements indicated tight binding between oligomers and chaperones. Moreover, atomic force microscopy imaging indicated that larger assemblies of oligomers are formed in the presence of the chaperones. This suggests that the chaperones bind to the oligomers and promote their assembly into larger species, with consequent shielding of the reactive surfaces and a decrease in their diffusional mobility. Overall, the data indicate a generic ability of chaperones to neutralize extracellular misfolded oligomers efficiently and reveal that further assembly of protein oligomers into larger species can be an effective strategy to neutralize such extracellular species.
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Registered trials
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.