Evidence map›Paper›PMID 26396193›Full record

ArticleThe Journal of biological chemistry2015

Small Molecules Detected by Second-Harmonic Generation Modulate the Conformation of Monomeric α-Synuclein and Reduce Its Aggregation in Cells.

Ben Moree, Guowei Yin, Diana F Lázaro, Francesca Munari, Timo Strohäker, Karin Giller, Stefan Becker, Tiago F Outeiro, Markus Zweckstetter, Joshua Salafsky

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing 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

24 citing papers in PubMed.

  1. Article
  2. Small molecules disaggregate alpha-synuclein and prevent seeding from patient brain-derived fibrils.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Second harmonic generation detection of Ras conformational changes and discovery of a small molecule binder.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  17. Article
  18. Plant Extracts and Phytochemicals TargetingFrontiers in pharmacology · 2018
    Review
  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

10 authors.

Ben MoreeFrom Biodesy, Inc., South San Francisco, California 94080.
Guowei Yinthe Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Diana F Lázarothe Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center, 37075 Göttingen, Germany, the Department of Neurodegeneration and Restorative Research, University Medical Center Göttingen, 37073 Göttingen, Germany, and.
Francesca Munarithe Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany, the German Center for Neurodegenerative Diseases (DZNE), 37077 Göttingen, Germany.
Timo Strohäkerthe Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Karin Gillerthe Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Stefan Beckerthe Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Tiago F Outeirothe Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center, 37075 Göttingen, Germany, the Department of Neurodegeneration and Restorative Research, University Medical Center Göttingen, 37073 Göttingen, Germany, and.
Markus Zweckstetterthe Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany, the German Center for Neurodegenerative Diseases (DZNE), 37077 Göttingen, Germany.
Joshua SalafskyFrom Biodesy, Inc., South San Francisco, California 94080, joshua.salafsky@biodesy.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteins are structurally dynamic molecules that perform specialized functions through unique conformational changes accessible in physiological environments. An ability to specifically and selectively control protein function via conformational modulation is an important goal for development of novel therapeutics and studies of protein mechanism in biological networks and disease. Here we applied a second-harmonic generation-based technique for studying protein conformation in solution and in real time to the intrinsically disordered, Parkinson disease related protein α-synuclein. From a fragment library, we identified small molecule modulators that bind to monomeric α-synuclein in vitro and significantly reduce α-synuclein aggregation in a neuronal cell culture model. Our results indicate that the conformation of α-synuclein is linked to the aggregation of protein in cells. They also provide support for a therapeutic strategy of targeting specific conformations of the protein to suppress or control its aggregation.

Indexed as

alpha-SynucleinAntiparkinson AgentsCell Line, TumorHumansLigandsNeuronsParkinson DiseaseProtein AggregatesProtein Aggregation, PathologicalProtein ConformationSmall Molecule Librariesalpha-SynucleinAntiparkinson AgentsLigandsProtein AggregatesSmall Molecule Librariesdrug discoveryParkinson diseaseprotein aggregationprotein conformationprotein drug interaction

Identifiers

PMID26396193
PMCPMC4646010

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.