ArticleCell reports2019
Filamentous Aggregates Are Fragmented by the Proteasome Holoenzyme.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- Stress-Induced Reorganization of Proteasomes Through Diffusion and Cytoskeleton-Dependent Mechanisms.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Deubiquitinating Enzymes Ubiquitin-Specific Proteases 7 and 10 Regulate TAU Aggregation.International journal of molecular sciences · 2025Article
- Beyond prion-like spreading in neurodegenerative disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- A chaperone-proteasome-based fragmentation machinery is essential for aggrephagy.Nature cell biology · 2025Article
- Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function.Cell · 2024Article
- Thermodynamic characterization of amyloid polymorphism by microfluidic transient incomplete separation.Chemical science · 2024Article
- Role of NFE2L1 in the Regulation of Proteostasis: Implications for Aging and Neurodegenerative Diseases.Biology · 2023Review
- Super-resolution imaging unveils the self-replication of tau aggregates upon seeding.Cell reports · 2023Article
- Dissecting aggregation and seeding dynamics of α-Syn polymorphs using the phasor approach to FLIM.Communications biology · 2022Article
- Quantitative super-resolution imaging of pathological aggregates reveals distinct toxicity profiles in different synucleinopathies.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Manipulating autophagic degradation in human diseases: from mechanisms to interventions.Life medicine · 2022Review
- Stability matters, too - the thermodynamics of amyloid fibril formation.Chemical science · 2022Review
- A Feasible Alternative Strategy Targeting Furin Disrupts SARS-CoV-2 Infection Cycle.Microbiology spectrum · 2022Article
- Mechanistic Models of Protein Aggregation Across Length-Scales and Time-Scales: From the Test Tube to Neurodegenerative Disease.Frontiers in neuroscience · 2022Review
- Computer Simulations Aimed at Exploring Protein Aggregation and Dissociation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- A Potential Mechanism for Targeting Aggregates With Proteasomes and Disaggregases in Liquid Droplets.Frontiers in aging neuroscience · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Filamentous aggregates (fibrils) are regarded as the final stage in the assembly of amyloidogenic proteins and are formed in many neurodegenerative diseases. Accumulation of aggregates occurs as a result of an imbalance between their formation and removal. Here we use single-aggregate imaging to show that large fibrils assembled from full-length tau are substrates of the 26S proteasome holoenzyme, which fragments them into small aggregates. Interestingly, although degradation of monomeric tau is not inhibited by adenosine 5'-(3-thiotriphosphate) (ATPγS), fibril fragmentation is predominantly dependent on the ATPase activity of the proteasome. The proteasome holoenzyme also targets fibrils assembled from α-synuclein, suggesting that its fibril-fragmenting function may be a general mechanism. The fragmented species produced by the proteasome shows significant toxicity to human cell lines compared with intact fibrils. Together, our results indicate that the proteasome holoenzyme possesses a fragmentation function that disassembles large fibrils into smaller and more cytotoxic 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.