Evidence map›Paper›PMID 26601940›Full record

ArticleThe Journal of biological chemistry2016

What Can the Kinetics of Amyloid Fibril Formation Tell about Off-pathway Aggregation?

Rosa Crespo, Eva Villar-Alvarez, Pablo Taboada, Fernando A Rocha, Ana M Damas, Pedro M Martins

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed.

  1. Article
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  6. Mechanisms and pathology of protein misfolding and aggregation.Nature reviews. Molecular cell biology · 2023
    Review
  7. Article
  8. A Biomimetic Multiparametric Assay to Characterise Anti-Amyloid Drugs.International journal of molecular sciences · 2023
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Small molecule induced toxic human-IAPP species characterized by NMR.Chemical communications (Cambridge, England) · 2020
    Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
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

6 authors.

Rosa CrespoFrom the Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia, Departamento de Engenharia Química, Faculdade de Engenharia da Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
Eva Villar-Alvarezthe Departamento de Física de la Materia Condensada, Facultad de Física, Universidad de Santiago de Compostela, 15782 Spain, and.
Pablo Taboadathe Departamento de Física de la Materia Condensada, Facultad de Física, Universidad de Santiago de Compostela, 15782 Spain, and.
Fernando A RochaFrom the Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia, Departamento de Engenharia Química, Faculdade de Engenharia da Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
Ana M Damasthe Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
Pedro M MartinsFrom the Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia, Departamento de Engenharia Química, Faculdade de Engenharia da Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal,; the Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal. Electronic address: pmmartins@icbas.up.pt.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Some of the most prevalent neurodegenerative diseases are characterized by the accumulation of amyloid fibrils in organs and tissues. Although the pathogenic role of these fibrils has not been completely established, increasing evidence suggests off-pathway aggregation as a source of toxic/detoxicating deposits that still remains to be targeted. The present work is a step toward the development of off-pathway modulators using the same amyloid-specific dyes as those conventionally employed to screen amyloid inhibitors. We identified a series of kinetic signatures revealing the quantitative importance of off-pathway aggregation relative to amyloid fibrillization; these include non-linear semilog plots of amyloid progress curves, highly variable end point signals, and half-life coordinates weakly influenced by concentration. Molecules that attenuate/intensify the magnitude of these signals are considered promising off-pathway inhibitors/promoters. An illustrative example shows that amyloid deposits of lysozyme are only the tip of an iceberg hiding a crowd of insoluble aggregates. Thoroughly validated using advanced microscopy techniques and complementary measurements of dynamic light scattering, CD, and soluble protein depletion, the new analytical tools are compatible with the high-throughput methods currently employed in drug discovery.

Indexed as

AmyloidCircular DichroismHalf-LifeKineticsProtein AggregatesProtein Structure, TertiaryAmyloidProtein Aggregatesamyloidbiophysicsdrug screeningkineticsmathematical modelingprotein aggregation

Identifiers

PMID26601940
PMCPMC4722475

What OpenQuestion holds

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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.