Evidence map›Paper›PMID 36468184›Full record

ArticleEMBO molecular medicine2023

A novel phosphocholine-mimetic inhibits a pro-inflammatory conformational change in C-reactive protein.

Johannes Zeller, Karen S Cheung Tung Shing, Tracy L Nero, James D McFadyen, Guy Krippner, Balázs Bogner, Sheena Kreuzaler, Jurij Kiefer, Verena K Horner, David Braig and 13 more

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

37 citing papers in PubMed, 48 citations in OpenAlex.

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  11. C-reactive protein promotes diabetic kidney disease via Smad3-mediated NLRP3 inflammasome activation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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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

23 authors at 5 institutions in 3 countries.

Johannes Zeller *Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Medical Faculty of the University of Freiburg, Freiburg, Germany.ORCID 0000-0002-8122-9063
Karen S Cheung Tung Shing *Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Vic., Australia.ORCID 0000-0002-3817-0860
Tracy L NeroDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Vic., Australia.ORCID 0000-0002-3393-1843
James D McFadyenBaker Heart and Diabetes Institute, Melbourne, Vic., Australia.ORCID 0000-0002-9832-6871
Guy KrippnerBaker Heart and Diabetes Institute, Melbourne, Vic., Australia.ORCID 0000-0003-0885-5217
Balázs BognerDepartment of Plastic and Hand Surgery, University of Freiburg Medical Centre, Medical Faculty of the University of Freiburg, Freiburg, Germany.
Sheena KreuzalerDepartment of Plastic and Hand Surgery, University of Freiburg Medical Centre, Medical Faculty of the University of Freiburg, Freiburg, Germany.
Jurij KieferDepartment of Plastic and Hand Surgery, University of Freiburg Medical Centre, Medical Faculty of the University of Freiburg, Freiburg, Germany.ORCID 0000-0002-1008-4522
Verena K HornerDepartment of Plastic and Hand Surgery, University of Freiburg Medical Centre, Medical Faculty of the University of Freiburg, Freiburg, Germany.
David BraigDepartment of Plastic and Hand Surgery, University of Freiburg Medical Centre, Medical Faculty of the University of Freiburg, Freiburg, Germany.ORCID 0000-0002-1267-0840
Habiba DanishBaker Heart and Diabetes Institute, Melbourne, Vic., Australia.
Sara BaratchiSchool of Health and Biomedical Sciences, RMIT University, Melbourne, Vic., Australia.ORCID 0000-0003-3588-7951
Mark FrickeDepartment of Plastic and Hand Surgery, University of Freiburg Medical Centre, Medical Faculty of the University of Freiburg, Freiburg, Germany.ORCID 0000-0003-1884-8600
Xiaowei WangBaker Heart and Diabetes Institute, Melbourne, Vic., Australia.ORCID 0000-0001-8658-7399
Michel G KatherCentre for Integrative Signalling Analysis CISA, University of Freiburg, Freiburg, Germany.ORCID 0000-0002-3521-2308
Bernd KammererCentre for Integrative Signalling Analysis CISA, University of Freiburg, Freiburg, Germany.ORCID 0000-0002-4631-8853
Kevin J WoollardCentre for Inflammatory Disease, Imperial College London, London, UK.ORCID 0000-0002-9839-5463
Prerna SharmaBaker Heart and Diabetes Institute, Melbourne, Vic., Australia.
Craig J MortonDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Vic., Australia.ORCID 0000-0001-5452-5193
Geoffrey PieterszBaker Heart and Diabetes Institute, Melbourne, Vic., Australia.ORCID 0000-0002-1999-6835
Michael W Parker *Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Vic., Australia.ORCID 0000-0002-3101-1138
Karlheinz Peter *Baker Heart and Diabetes Institute, Melbourne, Vic., Australia.ORCID 0000-0002-8040-2258
Steffen U Eisenhardt *Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Medical Faculty of the University of Freiburg, Freiburg, Germany.ORCID 0000-0003-4471-3160
University of Freiburg · DEBaker Heart and Diabetes Institute · AUThe University of Melbourne · AUCentre for Inflammation Research · GBRMIT University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

C-reactive protein (CRP) is an early-stage acute phase protein and highly upregulated in response to inflammatory reactions. We recently identified a novel mechanism that leads to a conformational change from the native, functionally relatively inert, pentameric CRP (pCRP) structure to a pentameric CRP intermediate (pCRP*) and ultimately to the monomeric CRP (mCRP) form, both exhibiting highly pro-inflammatory effects. This transition in the inflammatory profile of CRP is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine lipid head groups. We designed a tool compound as a low molecular weight CRP inhibitor using the structure of phosphocholine as a template. X-ray crystallography revealed specific binding to the phosphocholine binding pockets of pCRP. We provide in vitro and in vivo proof-of-concept data demonstrating that the low molecular weight tool compound inhibits CRP-driven exacerbation of local inflammatory responses, while potentially preserving pathogen-defense functions of CRP. The inhibition of the conformational change generating pro-inflammatory CRP isoforms via phosphocholine-mimicking compounds represents a promising, potentially broadly applicable anti-inflammatory therapy.

Indexed as

C-Reactive ProteinPhosphorylcholineAnti-Inflammatory AgentsCell MembraneHumansInflammationAnti-Inflammatory AgentsC-Reactive ProteinPhosphorylcholineanti-inflammatory therapyC-reactive proteindrug developmentischemiareperfusion injuryx-ray crystallography

Identifiers

PMID36468184
PMCPMC9832874
OpenAlexW4310707209

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.