Evidence map›Paper›PMID 22586108›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation in the absence of nucleic acids.

Nathan R Deleault, Justin R Piro, Daniel J Walsh, Fei Wang, Jiyan Ma, James C Geoghegan, Surachai Supattapone

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers.

0numbers the graph read from it
0cells of the map it votes in
163citing papers in PubMed
11.0field-weighted citation impact, top 1% 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

163 citing papers in PubMed, 239 citations in OpenAlex.

  1. Trial
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  9. Article
  10. Review
  11. Tracking Prions by RT-QuIC: An Update.Sub-cellular biochemistry · 2025
    Review
  12. Article
  13. RNA as a component of scrapie fibrils.Scientific reports · 2024
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

103 more citing papers are in PubMed but not listed here.

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 1 country.

Nathan R DeleaultDepartment of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
Justin R Piro
Daniel J Walsh
Fei Wang
Jiyan Ma
James C Geoghegan
Surachai Supattapone
The Ohio State University · USDartmouth College · US

Funding

Origin and Mechanism of Promiscuous Prion StrainsR01NS046478 · NINDS · DARTMOUTH COLLEGE · PI SUPATTAPONE, SURACHAI · 2004 to 2017
$5.0M
To investigate the contributions of lipid membranes to prion diseaseR01NS060729 · NINDS · VAN ANDEL RESEARCH INSTITUTE · PI MA, JIYAN, SUREWICZ, WITOLD K · 2008 to 2017
$4.5M
Molecular Mechanism of Prion StrainR01NS071035 · NINDS · VAN ANDEL RESEARCH INSTITUTE · PI MA, JIYAN · 2011 to 2015
$1.8M
Biochemistry of Infectious PrionsR01NS055875 · NINDS · DARTMOUTH COLLEGE · PI SUPATTAPONE, SURACHAI · 2007 to 2011
$1.4M
NINDS NIH HHS 2R01 NS046478NINDS NIH HHS R01 NS046478NINDS NIH HHS R01 NS055875NINDS NIH HHS R01 NS060729NINDS NIH HHS R01 NS071035
6 · The paper itself

Abstract

Infectious prions containing the pathogenic conformer of the mammalian prion protein (PrP(Sc)) can be produced de novo from a mixture of the normal conformer (PrP(C)) with RNA and lipid molecules. Recent reconstitution studies indicate that nucleic acids are not required for the propagation of mouse prions in vitro, suggesting the existence of an alternative prion propagation cofactor in brain tissue. However, the identity and functional properties of this unique cofactor are unknown. Here, we show by purification and reconstitution that the molecule responsible for the nuclease-resistant cofactor activity in brain is endogenous phosphatidylethanolamine (PE). Synthetic PE alone facilitates conversion of purified recombinant (rec)PrP substrate into infectious recPrP(Sc) molecules. Other phospholipids, including phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and phosphatidylglycerol, were unable to facilitate recPrP(Sc) formation in the absence of RNA. PE facilitated the propagation of PrP(Sc) molecules derived from all four different animal species tested including mouse, suggesting that unlike RNA, PE is a promiscuous cofactor for PrP(Sc) formation in vitro. Phospholipase treatment abolished the ability of brain homogenate to reconstitute the propagation of both mouse and hamster PrP(Sc) molecules. Our results identify a single endogenous cofactor able to facilitate the formation of prions from multiple species in the absence of nucleic acids or other polyanions.

Indexed as

AnimalsBlotting, WesternBrainCricetinaeImmunohistochemistryMiceNucleic AcidsPhosphatidylcholinesPhosphatidylethanolaminesPhosphatidylglycerolsPhosphatidylinositolsPhosphatidylserinesPrionsProtein FoldingRecombinant ProteinsRNANucleic AcidsPhosphatidylcholinesphosphatidylethanolaminePhosphatidylethanolaminesPhosphatidylglycerolsPhosphatidylinositolsPhosphatidylserinesPrionsRecombinant ProteinsRNA

Identifiers

PMID22586108
PMCPMC3365173
OpenAlexW2070878385

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.