Evidence map›Paper›PMID 24843046›Full record

ArticleThe EMBO journal2014

Identification of a gene regulatory network associated with prion replication.

Masue M Marbiah, Anna Harvey, Billy T West, Anais Louzolo, Priya Banerjee, Jack Alden, Anita Grigoriadis, Holger Hummerich, Ho-Man Kan, Ying Cai and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

38 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. A scalable, dividing cell model for the robust propagation and quantification of human sporadic Creutzfeldt-Jakob disease prions.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Astrocyte in prion disease: a double-edged sword.Neural regeneration research · 2022
    Review
  19. Review
  20. Prions and prion diseases: Insights from the eye.Experimental eye research · 2020
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 4 countries.

Masue M MarbiahMRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology Queen Square, London, UK.
Anna HarveyMRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology Queen Square, London, UK.
Billy T WestMRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology Queen Square, London, UK.
Anais LouzoloDepartment of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Priya BanerjeeBiomedical Communications, Terrence Donnelly Health Sciences Complex University of Toronto, Toronto, ON, Canada.
Jack AldenMRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology Queen Square, London, UK.
Anita GrigoriadisBreakthrough Breast Cancer Research Unit, Research Oncology, Guy's Hospital, London, UK.
Holger HummerichMRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology Queen Square, London, UK.
Ho-Man KanDepartment of Biology, University of Virginia, Charlottesville, VA, USA.
Ying CaiDepartment of Biology, University of Virginia, Charlottesville, VA, USA.
George S BloomDepartment of Biology, University of Virginia, Charlottesville, VA, USA.
Parmjit JatMRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology Queen Square, London, UK.
John CollingeMRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology Queen Square, London, UK.
Peter-Christian KlöhnMRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology Queen Square, London, UK p.kloehn@prion.ucl.ac.uk.
National Hospital for Neurology and Neurosurgery · GBUniversity of Virginia · USMRC Prion Unit · GBGuy's Hospital · GBKarolinska Institutet · SEUniversity College London · GBUniversity of Toronto · CA

Funding

Regulation of Actin Assembly and Cell Motility by IQGAPsR01NS051746 · NINDS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI BLOOM, GEORGE S · 2005 to 2009
$1.7M
Medical Research Council MC_U123182016Medical Research Council MC_U123192748NINDS NIH HHS R01 NS051746
6 · The paper itself

Abstract

Prions consist of aggregates of abnormal conformers of the cellular prion protein (PrP(C)). They propagate by recruiting host-encoded PrP(C) although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrP(C) expression differences, to identify such factors. Transcriptome analysis of prion-resistant revertants, isolated from highly susceptible cells, revealed a gene expression signature associated with susceptibility and modulated by differentiation. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease-related PrP is deposited. Silencing nine of these genes significantly increased susceptibility. Silencing of Papss2 led to undersulphated heparan sulphate and increased PrP(C) deposition at the ECM, concomitantly with increased prion propagation. Moreover, inhibition of fibronectin 1 binding to integrin α8 by RGD peptide inhibited metalloproteinases (MMP)-2/9 whilst increasing prion propagation. In summary, we have identified a gene regulatory network associated with prion propagation at the ECM and governed by the cellular differentiation state.

Indexed as

Models, MolecularAnimalsCell DifferentiationCloning, MolecularExtracellular MatrixFlow CytometryGene Regulatory NetworksHumansMiceMicroarray AnalysisMicroscopy, FluorescencePrionsPrPC Proteinsras GTPase-Activating ProteinsReal-Time Polymerase Chain ReactionRNA, Small InterferingIQGAP2 protein, humanPrionsPrPC Proteinsras GTPase-Activating ProteinsRNA, Small Interferingextracellular matrixintegrinneurodegenerationprion diseasesscrapie

Identifiers

PMID24843046
PMCPMC4198050
OpenAlexW2107784996

What OpenQuestion holds

Textmetadata
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.