Evidence map›Paper›PMID 29703933›Full record

ArticleNature communications2018

The cysteine-reactive small molecule ebselen facilitates effective SOD1 maturation.

Michael J Capper, Gareth S A Wright, Letizia Barbieri, Enrico Luchinat, Eleonora Mercatelli, Luke McAlary, Justin J Yerbury, Paul M O'Neill, Svetlana V Antonyuk, Lucia Banci and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
8.3field-weighted citation impact, top 2% of its field
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

50 citing papers in PubMed, 119 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Nose-to-brain delivery of a SOD1-stabilizing small molecule ameliorates pathology in an ALS mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  5. Article
  6. Efficacy of selenium- and tellurium-based organocompounds against ruminant gastrointestinal nematodes in vitro.Revista brasileira de parasitologia veterinaria = Brazilian journal of veterinary parasitology : Orgao Oficial do Colegio Brasileiro de Parasitologia Veterinaria · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Structural insights into the role of reduced cysteine residues in SOD1 amyloid filament formation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Neurological Diseases can be Regulated by Phase Separation.Reviews of physiology, biochemistry and pharmacology · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. Ligand-Based Competition Binding by Real-TimeJournal of medicinal chemistry · 2024
    Article
  17. Article
  18. Article
  19. Review
  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

11 authors at 3 institutions in 3 countries.

Michael J CapperMolecular Biophysics Group, Institute of Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, L69 7ZB, UK.
Gareth S A WrightMolecular Biophysics Group, Institute of Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, L69 7ZB, UK.
Letizia BarbieriMagnetic Resonance Centre (CERM), University of Florence, 50019, Sesto Fiorentino, Italy.
Enrico LuchinatMagnetic Resonance Centre (CERM), University of Florence, 50019, Sesto Fiorentino, Italy.ORCID http://orcid.org/0000-0003-4183-4311
Eleonora MercatelliMagnetic Resonance Centre (CERM), University of Florence, 50019, Sesto Fiorentino, Italy.
Luke McAlaryIllawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia.
Justin J YerburyIllawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia.ORCID http://orcid.org/0000-0003-2528-7039
Paul M O'NeillDepartment of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.
Svetlana V AntonyukMolecular Biophysics Group, Institute of Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, L69 7ZB, UK.ORCID http://orcid.org/0000-0002-2779-9946
Lucia BanciMagnetic Resonance Centre (CERM), University of Florence, 50019, Sesto Fiorentino, Italy. banci@cerm.unifi.it.
S Samar HasnainMolecular Biophysics Group, Institute of Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, L69 7ZB, UK. s.s.hasnain@liverpool.ac.uk.
University of Liverpool · GBInteruniversity Consortium for Magnetic Resonance · ITUniversity of Wollongong · AU

Funding

Motor Neurone Disease Association HASNAIN/APR15/833-791MRF_ MRF-060-0002-RG-HASNA(60)MRF_ MRF-085-0001-CTA-HASNA
6 · The paper itself

Abstract

Superoxide dismutase-1 (SOD1) mutants, including those with unaltered enzymatic activity, are known to cause amyotrophic lateral sclerosis (ALS). Several destabilizing factors contribute to pathogenicity including a reduced ability to complete the normal maturation process which comprises folding, metal cofactor acquisition, intra-subunit disulphide bond formation and dimerization. Immature SOD1 forms toxic oligomers and characteristic large insoluble aggregates within motor system cells. Here we report that the cysteine-reactive molecule ebselen efficiently confers the SOD1 intra-subunit disulphide and directs correct SOD1 folding, depopulating the globally unfolded precursor associated with aggregation and toxicity. Assisted formation of the unusual SOD1 cytosolic disulphide bond could have potential therapeutic applications. In less reducing environments, ebselen forms a selenylsulphide with Cys111 and restores the monomer-dimer equilibrium of A4V SOD1 to wild-type. Ebselen is therefore a potent bifunctional pharmacological chaperone for SOD1 that combines properties of the SOD1 chaperone hCCS and the recently licenced antioxidant drug, edaravone.

Indexed as

Amyotrophic Lateral SclerosisAntioxidantsAsthmaAzolesCrystallography, X-RayCysteineDisulfidesEdaravoneHEK293 CellsHumansIsoindolesMolecular ChaperonesMutationNuclear Magnetic Resonance, BiomolecularOrganoselenium CompoundsProtein BindingAntioxidantsAzolesCCS protein, humanCysteineDisulfidesebselenEdaravoneIsoindolesMolecular ChaperonesOrganoselenium CompoundsSOD1 protein, humanSuperoxide Dismutase-1

Identifiers

PMID29703933
PMCPMC5923229
OpenAlexW2801398196

What OpenQuestion holds

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LicenceCC BY
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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.