Evidence map›Paper›PMID 30741954›Full record

ArticleScientific reports2019

Early stages of aggregation of engineered α-synuclein monomers and oligomers in solution.

Xi Li, Chunhua Dong, Marion Hoffmann, Craig R Garen, Leonardo M Cortez, Nils O Petersen, Michael T Woodside

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Synucleinopathies: Intrinsic and Extrinsic Factors.Cell biochemistry and biophysics · 2023
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Wild-TypeFrontiers in molecular biosciences · 2022
    Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. All-or-none amyloid disassembly via chaperone-triggered fibril unzipping favors clearance of α-synuclein toxic species.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  17. Review
  18. Defining the Neuropathological Aggresome acrossThe journal of physical chemistry. B · 2021
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Xi LiDepartment of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada.
Chunhua DongDepartment of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada.
Marion HoffmannDepartment of Physics, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
Craig R GarenDepartment of Physics, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
Leonardo M CortezDivision of Neurology, Department of Medicine, Centre for Prions and Protein Folding Diseases, and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, T6G 2M8, Canada.
Nils O PetersenDepartment of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada. nilsp@ualberta.ca.
Michael T WoodsideDepartment of Physics, University of Alberta, Edmonton, AB, T6G 2E1, Canada. michael.woodside@ualberta.ca.ORCID 0000-0003-4695-0397

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

α-Synuclein is a protein that aggregates as amyloid fibrils in the brains of patients with Parkinson's disease and dementia with Lewy bodies. Small oligomers of α-synuclein are neurotoxic and are thought to be closely associated with disease. Whereas α-synuclein fibrillization and fibril morphologies have been studied extensively with various methods, the earliest stages of aggregation and the properties of oligomeric intermediates are less well understood because few methods are able to detect and characterize early-stage aggregates. We used fluorescence spectroscopy to investigate the early stages of aggregation by studying pairwise interactions between α-synuclein monomers, as well as between engineered tandem oligomers of various sizes (dimers, tetramers, and octamers). The hydrodynamic radii of these engineered α-synuclein species were first determined by fluorescence correlation spectroscopy and dynamic light scattering. The rate of pairwise aggregation between different species was then monitored using dual-color fluorescence cross-correlation spectroscopy, measuring the extent of association between species labelled with different dyes at various time points during the early aggregation process. The aggregation rate and extent increased with tandem oligomer size. Self-association of the tandem oligomers was found to be the preferred pathway to form larger aggregates: interactions between oligomers occurred faster and to a greater extent than interactions between oligomers and monomers, indicating that the oligomers were not as efficient in seeding further aggregation by addition of monomers. These results suggest that oligomer-oligomer interactions may play an important role in driving aggregation during its early stages.

Indexed as

Protein AggregatesProtein MultimerizationRecombinant Proteinsalpha-SynucleinGenetic EngineeringHumansKineticsProtein Aggregation, PathologicalSolubilityalpha-SynucleinProtein AggregatesRecombinant Proteins

Identifiers

PMID30741954
PMCPMC6370846

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Registered trials

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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.