Evidence map›Paper›PMID 19940127›Full record

ArticleThe Journal of biological chemistry2010

A novel, drug-based, cellular assay for the activity of neurotoxic mutants of the prion protein.

Tania Massignan, Richard S Stewart, Emiliano Biasini, Isaac H Solomon, Valentina Bonetto, Roberto Chiesa, David A Harris

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

26 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Mechanisms of prion-induced toxicity.Cell and tissue research · 2023
    Review
  4. Intrinsic toxicity of the cellular prion protein is regulated by its conserved central region.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
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  12. Article
  13. Article
  14. Article
  15. A mutant prion protein sensitizes neurons to glutamate-induced excitotoxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
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

7 authors at 2 institutions in 2 countries.

Tania MassignanDepartment of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Richard S Stewart
Emiliano Biasini
Isaac H Solomon
Valentina Bonetto
Roberto Chiesa
David A Harris
Washington University in St. Louis · USDulbecco Telethon Institute · IT

Funding

Mechanisms of Prion Protein ToxicityR01NS065244 · NINDS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HARRIS, DAVID A · 2010 to 2025
$8.9M
Washington University Center for Translational NeuroscienceP30NS057105 · NINDS · WASHINGTON UNIVERSITY · PI HOLTZMAN, DAVID M. · 2006 to 2011
$8.7M
MURINE TRANSGENIC MODELS OF PRION DISEASESR01NS040975 · NINDS · WASHINGTON UNIVERSITY · PI HARRIS, DAVID A · 2001 to 2015
$7.0M
Cellular Functions of the Prion ProteinR01NS052526 · NINDS · WASHINGTON UNIVERSITY · PI HARRIS, DAVID A · 2006 to 2010
$1.7M
NINDS NIH HHS NS040975NINDS NIH HHS NS052526NINDS NIH HHS P30 NS057105NINDS NIH HHS P30NS057105NINDS NIH HHS R01 NS040975NINDS NIH HHS R01 NS052526NINDS NIH HHS R01 NS065244Telethon GFP04007Telethon TCR08002Telethon TCR08005
6 · The paper itself

Abstract

In prion diseases, the infectious isoform of the prion protein (PrP(Sc)) may subvert a normal, physiological activity of the cellular isoform (PrP(C)). A deletion mutant of the prion protein (Delta105-125) that produces a neonatal lethal phenotype when expressed in transgenic mice provides a window into the normal function of PrP(C) and how it can be corrupted to produce neurotoxic effects. We report here the surprising and unexpected observation that cells expressing Delta105-125 PrP and related mutants are hypersensitive to the toxic effects of two classes of antibiotics (aminoglycosides and bleomycin analogues) that are commonly used for selection of stably transfected cell lines. This unusual phenomenon mimics several essential features of Delta105-125 PrP toxicity seen in transgenic mice, including rescue by co-expression of wild type PrP. Cells expressing Delta105-125 PrP are susceptible to drug toxicity within minutes, suggesting that the mutant protein enhances cellular accumulation of these cationic compounds. Our results establish a screenable cellular phenotype for the activity of neurotoxic forms of PrP, and they suggest possible mechanisms by which these molecules could produce their pathological effects in vivo.

Indexed as

PrPC ProteinsPrPSc ProteinsAmebicidesAnimalsAntibiotics, AntineoplasticBiological AssayBleomycinCell LineCell SurvivalCinnamatesDrug Evaluation, PreclinicalGentamicinsGPI-Linked ProteinsHumansHygromycin BMiceAmebicidesantibiotic G 418Antibiotics, AntineoplasticBleomycinCinnamatesGentamicinsGPI-Linked Proteinshygromycin AHygromycin BPrionsPRND protein, humanProtein IsoformsPrPC ProteinsPrPSc ProteinsZeocin

Identifiers

PMID19940127
PMCPMC2844219
OpenAlexW1990833847

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.