ArticlePLoS pathogens2017
Cross-seeding of prions by aggregated α-synuclein leads to transmissible spongiform encephalopathy.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Alpha-synuclein structural variants driving tau pathology and disease interaction.Neural regeneration research · 2026Article
- Amyloid-β, Tau Protein, α-Synuclein, TDP-43, and FUS in Mixed Pathology: And Intrinsic Disorder to Rule Them All.International journal of molecular sciences · 2026Review
- Tau Enhances Aggregation of S100A9 Protein and Further Association of Its Fibrils.International journal of molecular sciences · 2025Article
- Heterotypic Droplet Formation by Pro-Inflammatory S100A9 and Neurodegenerative Disease-Related α-Synuclein.Biomacromolecules · 2025Article
- Prion diseases: Lessons from historical outbreaks and potential emerging ones.Protein science : a publication of the Protein Society · 2025Review
- Liquid-liquid phase separation and conformational strains ofFrontiers in molecular neuroscience · 2024Review
- Conformation-Specific Association of Prion Protein Amyloid Aggregates with Tau Protein Monomers.International journal of molecular sciences · 2023Article
- Testing Antimicrobial Properties of Selected Short Amyloids.International journal of molecular sciences · 2023Article
- Amyloid Cross-Seeding: Mechanism, Implication, and Inhibition.Molecules (Basel, Switzerland) · 2022Review
- Spatiotemporal modulations in heterotypic condensates of prion and α-synuclein control phase transitions and amyloid conversion.Nature communications · 2022Article
- Combination of structure-based virtual screening, molecular docking and molecular dynamics approaches for the discovery of anti-prion fibril flavonoids.Frontiers in molecular biosciences · 2022Article
- Linking Parkinson's Disease and Melanoma: Interplay Between α-Synuclein and Pmel17 Amyloid Formation.Movement disorders : official journal of the Movement Disorder Society · 2021Review
- Lysozyme Fibrils Alter the Mechanism of Insulin Amyloid Aggregation.International journal of molecular sciences · 2021Article
- Biophysical processes underlying cross-seeding in amyloid aggregation and implications in amyloid pathology.Biophysical chemistry · 2021Review
- Multistep Changes in Amyloid Structure Induced by Cross-Seeding on a Rugged Energy Landscape.Biophysical journal · 2021Article
- Retina as a Model to Study In Vivo Transmission of α-Synuclein in the A53T Mouse Model of Parkinson's Disease.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Functional roles of the microbiota-gut-brain axis in Alzheimer's disease: Implications of gut microbiota-targeted therapy.Translational neuroscience · 2021Review
- A role of cellular translation regulation associated with toxic Huntingtin protein.Cellular and molecular life sciences : CMLS · 2020Article
- Article
- From Synaptic Protein to Prion: The Long and Controversial Journey of α-Synuclein.Frontiers in synaptic neuroscience · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Aggregation of misfolded proteins or peptides is a common feature of neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, prion and other diseases. Recent years have witnessed a growing number of reports of overlap in neuropathological features that were once thought to be unique to only one neurodegenerative disorder. However, the origin for the overlap remains unclear. One possibility is that diseases with mixed brain pathologies might arise from cross-seeding of one amyloidogenic protein by aggregated states of unrelated proteins. In the current study we examined whether prion replication can be induced by cross-seeding by α-synuclein or Aβ peptide. We found that α-synuclein aggregates formed in cultured cells or in vitro display cross-seeding activity and trigger misfolding of the prion protein (PrPC) in serial Protein Misfolding Cyclic Amplification reactions, producing self-replicating PrP states characterized by a short C-terminal proteinase K (PK)-resistant region referred to as PrPres. Non-fibrillar α-synuclein or fibrillar Aβ failed to cross-seed misfolding of PrPC. Remarkably, PrPres triggered by aggregated α-synuclein in vitro propagated in animals and, upon serial transmission, produced PrPSc and clinical prion disease characterized by spongiosis and astrocytic gliosis. The current study demonstrates that aggregated α-synuclein is potent in cross-seeding of prion protein misfolding and aggregation in vitro, producing self-replicating states that can lead to transmissible prion diseases upon serial passaging in wild type animals. In summary, the current work documents direct cross-seeding between unrelated amyloidogenic proteins associated with different neurodegenerative diseases. This study suggests that early interaction between unrelated amyloidogenic proteins might underlie the etiology of mixed neurodegenerative proteinopathies.
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Registered trials
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