ArticlePrion
The metazoan protein disaggregase and amyloid depolymerase system: Hsp110, Hsp70, Hsp40, and small heat shock proteins.
Article in Prion. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 74 citations in OpenAlex.
- Protein disulfide isomerase dissolves and detoxifies oligomeric assemblies of amyloid beta peptide.FEBS letters · 2026Article
- Article
- Direct and Indirect Protein Interactions Link FUS Aggregation to Histone Post-Translational Modification Dysregulation and Growth Suppression in an ALS/FTD Yeast Model.Journal of fungi (Basel, Switzerland) · 2025Article
- Decoding chaperone complexes: Insights from NMR spectroscopy.Biophysics reviews · 2024Review
- Characterization of a New Hsp110 Inhibitor as a Potential Antifungal.Journal of fungi (Basel, Switzerland) · 2024Article
- Protein aggregation and biomolecular condensation in hypoxic environments (Review).International journal of molecular medicine · 2024Review
- A first-in-class inhibitor of Hsp110 molecular chaperones of pathogenic fungi.Nature communications · 2023Article
- Protein Misfolding and Aggregation in Proteinopathies: Causes, Mechanism and Cellular Response.Diseases (Basel, Switzerland) · 2023Review
- Prion-Like Proteins in Phase Separation and Their Link to Disease.Biomolecules · 2021Review
- Purification and biochemical characterization of Msi3, an essential Hsp110 molecular chaperone in Candida albicans.Cell stress & chaperones · 2021Article
- Higher-order organization of biomolecular condensates.Open biology · 2021Review
- (Dis)Solving the problem of aberrant protein states.Disease models & mechanisms · 2021Review
- Physiological and proteomic profiles of Trypanosoma brucei rhodesiense parasite isolated from suramin responsive and non-responsive HAT patients in Busoga, Uganda.International journal for parasitology. Drugs and drug resistance · 2021Article
- Combating deleterious phase transitions in neurodegenerative disease.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Article
- The ABCF gene family facilitates disaggregation during animal development.Molecular biology of the cell · 2020Review
- Reversal of Alpha-Synuclein Fibrillization by Protein Disulfide Isomerase.Frontiers in cell and developmental biology · 2020Article
- Come Together: Protein Assemblies, Aggregates and the Sarcostat at the Heart of Cardiac Myocyte Homeostasis.Frontiers in physiology · 2020Review
- Yeast Models for Amyloids and Prions: Environmental Modulation and Drug Discovery.Molecules (Basel, Switzerland) · 2019Review
- Spiraling in Control: Structures and Mechanisms of the Hsp104 Disaggregase.Cold Spring Harbor perspectives in biology · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
A baffling aspect of metazoan proteostasis is the lack of an Hsp104 ortholog that rapidly disaggregates and reactivates misfolded polypeptides trapped in stress induced disordered aggregates, preamyloid oligomers, or amyloid fibrils. By contrast, in bacteria, protozoa, chromista, fungi, and plants, Hsp104 orthologs are highly conserved and confer huge selective advantages in stress tolerance. Moreover, in fungi, the amyloid remodeling activity of Hsp104 has enabled deployment of prions for various beneficial modalities. Thus, a longstanding conundrum has remained unanswered: how do metazoan cells renature aggregated proteins or resolve amyloid fibrils without Hsp104? Here, we highlight recent advances that unveil the metazoan protein-disaggregase machinery, comprising Hsp110, Hsp70, and Hsp40, which synergize to dissolve disordered aggregates, but are unable to rapidly solubilize stable amyloid fibrils. However, Hsp110, Hsp70, and Hsp40 exploit the slow monomer exchange dynamics of amyloid, and can slowly depolymerize amyloid fibrils from their ends in a manner that is stimulated by small heat shock proteins. Upregulation of this system could have key therapeutic applications in various protein-misfolding disorders. Intriguingly, yeast Hsp104 can interface with metazoan Hsp110, Hsp70, and Hsp40 to rapidly eliminate disease associated amyloid. Thus, metazoan proteostasis is receptive to augmentation with exogenous disaggregases, which opens a number of therapeutic opportunities.
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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.