Evidence map›Paper›PMID 42533105›Full record

ArticleNature structural & molecular biology2026

Protein thiol alterations drive pathologic liquid-liquid phase separation in the aging brain.

Thibaut Vignane, Martín Hugo, Christian Hoffmann, Polina Reichert, Antonia Katsouda, Davide D'Andrea, Han Wang, Johannes V Tromm, Marko Miler, Ferran Comas and 23 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature structural & molecular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Protein oxidation in crowded environments.The Biochemical journal · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. 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

33 authors.

Thibaut VignaneLeibniz Institute for Analytical Sciences, ISAS, e.V., Dortmund, Germany. vignane@med.uni-frankfurt.de.ORCID http://orcid.org/0000-0002-3377-3187
Martín Hugo *Leibniz Institute for Analytical Sciences, ISAS, e.V., Dortmund, Germany.ORCID http://orcid.org/0000-0003-3430-6457
Christian Hoffmann *Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0003-3478-2410
Polina Reichert *School of Molecular Biosciences, MVLS College, University of Glasgow, Glasgow, UK.
Antonia KatsoudaClinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Davide D'AndreaSchool of Molecular Biosciences, MVLS College, University of Glasgow, Glasgow, UK.
Han WangInstitute of Biochemistry, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0009-0000-5517-3038
Johannes V TrommInstitute of Biochemistry, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.
Marko MilerLeibniz Institute for Analytical Sciences, ISAS, e.V., Dortmund, Germany.
Ferran ComasLeibniz Institute for Analytical Sciences, ISAS, e.V., Dortmund, Germany.
Dunja PetrovicLeibniz Institute for Analytical Sciences, ISAS, e.V., Dortmund, Germany.
Suyuan ChenLeibniz Institute for Analytical Sciences, ISAS, e.V., Dortmund, Germany.
Jan Lj MiljkovicMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-1910-9677
Danail StoychevSchool of Molecular Biosciences, MVLS College, University of Glasgow, Glasgow, UK.
Erik LackoSchool of Molecular Biosciences, MVLS College, University of Glasgow, Glasgow, UK.
Vladimir M JovanovicBioinformatics Solution Center, Institute for Informatics, Freie Universität Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-8056-5065
Suwarna ChakrabortyDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sunil J TripathiDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-9107-2437
Edwin Vázquez-RosaDepartment of Psychiatry, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0009-0005-4508-5217
Jordan L MorrisMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
Suvagata Roy ChowdhuryMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
Julien PrudentMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-3821-6088
Albert SickmannLeibniz Institute for Analytical Sciences, ISAS, e.V., Dortmund, Germany.ORCID http://orcid.org/0000-0002-2388-5265
Natalija PolovicDepartment of Biochemistry, Faculty of Chemistry, University of Belgrade, Belgrade, Serbia.ORCID http://orcid.org/0000-0002-9127-2014
Andrew A PieperDepartment of Psychiatry, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0000-0001-6299-6577
Ilan DavisSchool of Molecular Biosciences, MVLS College, University of Glasgow, Glasgow, UK.
Kostas TokatlidisSchool of Molecular Biosciences, MVLS College, University of Glasgow, Glasgow, UK.
Bindu D PaulDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-1862-6103
Michael P MurphyMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-1115-9618
Christian MünchInstitute of Molecular Systems Medicine, Faculty of Medicine, Goethe University, Frankfurt, Germany.ORCID http://orcid.org/0000-0003-3832-090X
Andreas PapapetropoulosClinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.ORCID http://orcid.org/0000-0002-4253-5930
Dragomir MilovanovicInstitute of Biochemistry, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0002-6625-1879
Milos R FilipovicLeibniz Institute for Analytical Sciences, ISAS, e.V., Dortmund, Germany. milos.filipovic@glasgow.ac.uk.ORCID http://orcid.org/0000-0003-0060-0041

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cellular homeostasis relies on regulation of processes, including protein post-translational modifications (PTMs) and biomolecular condensation. Aging disrupts the equilibrium of these processes, increasing susceptibility to disease and mortality. Here we used chemoproteomic techniques to generate an atlas of cysteine PTMs in the mouse brain and showed that age-related increases in thiol oxidation promoted the formation of biomolecular condensates. By contrast, protein persulfidation, regulated by hydrogen sulfide production, inhibited biomolecular condensation, preserving protein function. Age-induced alterations in cysteine PTMs influenced the phase separation properties of synapsin 1 and G3BP2, leading to impaired neurotransmitter release and defective stress granule formation and resolution, features associated with aging and neurodegenerative diseases. Mice deficient in cystathionine γ-lyase, the enzyme responsible for hydrogen sulfide production, exhibited reduced lifespans and spontaneously developed protein aggregates with age. Our results highlight the therapeutic potential of protein persulfidation in reversal of dysregulated biomolecular condensation and suggest that sulfide donors could be used to mitigate age-related diseases.

Indexed as

AgingBrainSulfhydryl CompoundsAnimalsBiomolecular CondensatesCystathionine gamma-LyaseCysteineHydrogen SulfideMiceNeurodegenerative DiseasesOxidation-ReductionPhase SeparationProtein Processing, Post-TranslationalStress GranulesCystathionine gamma-LyaseCysteineHydrogen SulfideSulfhydryl Compounds

Identifiers

PMID42533105
PMCPMC13468144

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.