Evidence map›Paper›PMID 36224378›Full record

ArticleNature structural & molecular biology2022

Global, in situ analysis of the structural proteome in individuals with Parkinson's disease to identify a new class of biomarker.

Marie-Therese Mackmull, Luise Nagel, Fabian Sesterhenn, Jan Muntel, Jan Grossbach, Patrick Stalder, Roland Bruderer, Lukas Reiter, Wilma D J van de Berg, Natalie de Souza and 2 more

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In one paragraph

Article in Nature structural & molecular biology, 2022. 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
5.8field-weighted citation impact, top 3% 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

24 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. State-of-the-Art and Future Directions in Structural Proteomics.Molecular & cellular proteomics : MCP · 2025
    Review
  8. Article
  9. Article
  10. Analysis of Limited Proteolysis-Coupled Mass Spectrometry Data.Molecular & cellular proteomics : MCP · 2025
    Article
  11. Article
  12. Article
  13. Thioflavin T in-gel staining forFrontiers in molecular biosciences · 2025
    Article
  14. Recent Advances in Human Cerebrospinal Fluid Proteomics.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Marie-Therese Mackmull *Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.ORCID 0000-0003-2928-1144
Luise Nagel *Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Fabian SesterhennInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Jan MuntelBiognosys AG, Schlieren, Switzerland.ORCID 0000-0003-2320-5829
Jan GrossbachCluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.ORCID 0000-0002-9394-5665
Patrick StalderInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Roland BrudererBiognosys AG, Schlieren, Switzerland.
Lukas ReiterBiognosys AG, Schlieren, Switzerland.
Wilma D J van de BergAmsterdam UMC location Vrije Universiteit Amsterdam, Section Clinical Neuroanatomy and Biobanking, Department Anatomy and Neurosciences, Amsterdam, the Netherlands.
Natalie de SouzaInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Andreas BeyerCluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany. andreas.beyer@uni-koeln.de.ORCID 0000-0002-3891-2123
Paola PicottiInstitute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland. picotti@imsb.biol.ethz.ch.ORCID 0000-0002-4109-3552
ETH Zurich · CHBiognosys (Switzerland) · CHUniversity of Cologne · DEAmsterdam Neuroscience · NLTH Köln - University of Applied Sciences · DEUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disease for which robust biomarkers are needed. Because protein structure reflects function, we tested whether global, in situ analysis of protein structural changes provides insight into PD pathophysiology and could inform a new concept of structural disease biomarkers. Using limited proteolysis-mass spectrometry (LiP-MS), we identified 76 structurally altered proteins in cerebrospinal fluid (CSF) of individuals with PD relative to healthy donors. These proteins were enriched in processes misregulated in PD, and some proteins also showed structural changes in PD brain samples. CSF protein structural information outperformed abundance information in discriminating between healthy participants and those with PD and improved the discriminatory performance of CSF measures of the hallmark PD protein α-synuclein. We also present the first analysis of inter-individual variability of a structural proteome in healthy individuals, identifying biophysical features of variable protein regions. Although independent validation is needed, our data suggest that global analyses of the human structural proteome will guide the development of novel structural biomarkers of disease and enable hypothesis generation about underlying disease processes.

Indexed as

Neurodegenerative DiseasesParkinson Diseasealpha-SynucleinBiomarkersHumansProteomealpha-SynucleinBiomarkersProteome

Identifiers

PMID36224378
OpenAlexW4304695273

What OpenQuestion holds

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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.