ArticleeLife2020
Therapeutic genetic variation revealed in diverse Hsp104 homologs.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- High-throughput screening approach identifies substrate-selective Hsp104 variants that counter amyloid seeding with diminished off-target effects.Molecular cell · 2026Article
- Multilayer modulation of the proteasome: new strategies for neuroprotection.Frontiers in molecular neuroscience · 2026Article
- A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies inJournal of fungi (Basel, Switzerland) · 2025Review
- Design principles to tailor Hsp104 therapeutics.Cell reports · 2024Article
- The middle domain of Hsp104 can ensure substrates are functional after processing.PLoS genetics · 2024Article
- Design principles to tailor Hsp104 therapeutics.bioRxiv : the preprint server for biology · 2024Article
- CRISPR screen for protein inclusion formation uncovers a role for SRRD in the regulation of intermediate filament dynamics and aggresome assembly.PLoS genetics · 2024Article
- Human herpesvirus 8 ORF57 protein is able to reduce TDP-43 pathology: network analysis identifies interacting pathways.Human molecular genetics · 2023Article
- Tuning Hsp104 specificity to selectively detoxify α-synuclein.Molecular cell · 2023Article
- Overexpression of Hsp104 by Causing Dissolution of the Prion Seeds Cures the Yeast [International journal of molecular sciences · 2023Article
- Glia in FTLD-GRN: from supporting cast to leading role.The Journal of clinical investigation · 2023Article
- Cytoplasmic molecular chaperones in Pseudomonas species.Journal of microbiology (Seoul, Korea) · 2022Review
- Hsp104 N-terminal domain interaction with substrates plays a regulatory role in protein disaggregation.The FEBS journal · 2022Article
- Regulating Phase Transition in Neurodegenerative Diseases by Nuclear Import Receptors.Biology · 2022Review
- The yeast molecular chaperone, Hsp104, influences transthyretin aggregate formation.Frontiers in molecular neuroscience · 2022Article
- Amyloid Fragmentation and Disaggregation in Yeast and Animals.Biomolecules · 2021Review
- Prion-Like Proteins in Phase Separation and Their Link to Disease.Biomolecules · 2021Review
- (Dis)Solving the problem of aberrant protein states.Disease models & mechanisms · 2021Review
- Combating deleterious phase transitions in neurodegenerative disease.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Horizontal Transmission of Stress Resistance Genes Shape the Ecology of Beta- and Gamma-Proteobacteria.Frontiers in microbiology · 2021Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
The AAA+ protein disaggregase, Hsp104, increases fitness under stress by reversing stress-induced protein aggregation. Natural Hsp104 variants might exist with enhanced, selective activity against neurodegenerative disease substrates. However, natural Hsp104 variation remains largely unexplored. Here, we screened a cross-kingdom collection of Hsp104 homologs in yeast proteotoxicity models. Prokaryotic ClpG reduced TDP-43, FUS, and α-synuclein toxicity, whereas prokaryotic ClpB and hyperactive variants were ineffective. We uncovered therapeutic genetic variation among eukaryotic Hsp104 homologs that specifically antagonized TDP-43 condensation and toxicity in yeast and TDP-43 aggregation in human cells. We also uncovered distinct eukaryotic Hsp104 homologs that selectively antagonized α-synuclein condensation and toxicity in yeast and dopaminergic neurodegeneration in
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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.