ReviewBiomolecules2020
From Seeds to Fibrils and Back: Fragmentation as an Overlooked Step in the Propagation of Prions and Prion-Like Proteins.
Review in Biomolecules, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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.
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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
16 citing papers in PubMed, 24 citations in OpenAlex.
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 2026Review
- Prions and protein aggregates as pathogens, self-propagating structures, biomarkers, and therapeutic targets.Microbiology and molecular biology reviews : MMBR · 2025Review
- Contrasting roles of autophagy in cellular prion infection.Autophagy · 2025Article
- Structural polymorphism of α-synuclein fibrils alters the pathway of Hsc70-mediated disaggregation.The EMBO journal · 2025Article
- Broken Balance: Emerging Cross-Talk Between Proteostasis and Lipostasis in Neurodegenerative Diseases.Cells · 2025Review
- Broken but not beaten: Challenge of reducing the amyloids pathogenicity by degradation.Journal of advanced research · 2025Review
- Cathepsin B prevents cell death by fragmentation and destruction of pathological amyloid fibrils.Cell death discovery · 2025Article
- Exposed Hsp70-binding site impacts yeast Sup35 prion disaggregation and propagation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Creutzfeldt-Jakob disease and other prion diseases.Nature reviews. Disease primers · 2024Review
- Vaccines for prion diseases: a realistic goal?Cell and tissue research · 2023Review
- Dissecting aggregation and seeding dynamics of α-Syn polymorphs using the phasor approach to FLIM.Communications biology · 2022Article
- Clearance of variant Creutzfeldt-Jakob disease prions in vivo by the Hsp70 disaggregase system.Brain : a journal of neurology · 2022Article
- Beyond Amyloid Fibers: Accumulation, Biological Relevance, and Regulation of Higher-Order Prion Architectures.Viruses · 2022Review
- Amyloid conformation-dependent disaggregation in a reconstituted yeast prion system.Nature chemical biology · 2022Article
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Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Many devastating neurodegenerative diseases are driven by the misfolding of normal proteins into a pathogenic abnormal conformation. Examples of such protein misfolding diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and prion diseases. The misfolded proteins involved in these diseases form self-templating oligomeric assemblies that recruit further correctly folded protein and induce their conversion. Over time, this leads to the formation of high molecular and mostly fibrillar aggregates that are increasingly inefficient at converting normal protein. Evidence from a multitude of in vitro models suggests that fibrils are fragmented to form new seeds, which can convert further normal protein and also spread to neighboring cells as observed in vivo. While fragmentation and seed generation were suggested as crucial steps in aggregate formation decades ago, the biological pathways involved remain largely unknown. Here, we show that mechanisms of aggregate clearance-namely the mammalian Hsp70-Hsp40-Hsp110 tri-chaperone system, macro-autophagy, and the proteasome system-may not only be protective, but also play a role in fragmentation. We further review the challenges that exist in determining the precise contribution of these mechanisms to protein misfolding diseases and suggest future directions to resolve these issues.
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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.