Evidence map›Paper›PMID 25695325›Full record

ArticleACS chemical biology2015

Mechanism of scrapie prion precipitation with phosphotungstate anions.

Dana J Levine, Jan Stöhr, Lillian E Falese, Julian Ollesch, Holger Wille, Stanley B Prusiner, Jeffrey R Long

Abstract read
In one paragraph

Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

21 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Article
  3. Prion Partitioning and Persistence in Environmental Waters.Environmental science & technology · 2025
    Article
  4. Article
  5. Review
  6. Guam ALS-PDC is a distinct double-prion disorder featuring both tau and Aβ prions.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. Aβ and Tau Prions Causing Alzheimer's Disease.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  8. Aβ and tau prions feature in the neuropathogenesis of Down syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  9. Article
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  11. Article
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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

7 authors at 3 institutions in 1 country.

Dana J Levine†Department of Chemistry, University of California, Berkeley, 211 Lewis Hall, Berkeley, California 94720, United States.
Jan Stöhr‡Institute for Neurodegenerative Diseases, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, California 94143, United States.
Lillian E Falese‡Institute for Neurodegenerative Diseases, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, California 94143, United States.
Julian Ollesch‡Institute for Neurodegenerative Diseases, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, California 94143, United States.
Holger Wille‡Institute for Neurodegenerative Diseases, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, California 94143, United States.
Stanley B Prusiner‡Institute for Neurodegenerative Diseases, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, California 94143, United States.
Jeffrey R Long†Department of Chemistry, University of California, Berkeley, 211 Lewis Hall, Berkeley, California 94720, United States.
University of California, San Francisco · USInstitute for Neurodegenerative Disorders · USUniversity of California, Berkeley · US

Funding

VIRAL DEGENERATIVE DEMENTING DISEASE IN AGING (SUPP)P01AG002132 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SALI, ANDREJ · 1985 to 2024
$51.7M
UNDERSTANDING AND IMPROVING SMALL MOLECULE INHIBITORS OF PRION REPLICATIONP01AG021601 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PRUSINER, STANLEY B · 2003 to 2013
$31.9M
SYNTHETIC AND RECOMBINANT PRP PEPTIDES AND PROTEINSP01AG010770 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PRUSINER, STANLEY B · 1993 to 2015
$30.3M
Univ of Calif Berkeley Chemistry-Biology Interface ProgramT32GM066698 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CHANG, CHRISTOPHER J., FRANCIS, MATTHEW B · 2004 to 2023
$7.5M
Towards Therapeutics for Neurodegenerative DiseasesR37AG031220 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PRUSINER, STANLEY B · 2008 to 2017
$6.2M
NIA NIH HHS AG002132NIA NIH HHS AG010770NIA NIH HHS AG021601NIA NIH HHS P01 AG002132NIA NIH HHS P01 AG010770NIA NIH HHS P01 AG021601NIA NIH HHS R37 AG031220NIGMS NIH HHS T32 GM066698PHS HHS SRR023679A
6 · The paper itself

Abstract

The phosphotungstate anion (PTA) is widely used to facilitate the precipitation of disease-causing prion protein (PrP(Sc)) from infected tissue for applications in structural studies and diagnostic approaches. However, the mechanism of this precipitation is not understood. In order to elucidate the nature of the PTA interaction with PrP(Sc) under physiological conditions, solutions of PTA were characterized by NMR spectroscopy at varying pH. At neutral pH, the parent [PW12O40](3-) ion decomposes to give a lacunary [PW11O39](7-) (PW11) complex and a single orthotungstate anion [WO4](2-) (WO4). To measure the efficacy of each component of PTA, increasing concentrations of PW11, WO4, and mixtures thereof were used to precipitate PrP(Sc) from brain homogenates of scrapie prion-infected mice. The amount of PrP(Sc) isolated, quantified by ELISA and immunoblotting, revealed that both PW11 and WO4 contribute to PrP(Sc) precipitation. Incubation with sarkosyl, PTA, or individual components of PTA resulted in separation of higher-density PrP aggregates from the neuronal lipid monosialotetrahexosylganglioside (GM1), as observed by sucrose gradient centrifugation. These experiments revealed that yield and purity of PrP(Sc) were greater with polyoxometalates (POMs), which substantially supported the separation of lipids from PrP(Sc) in the samples. Interaction of POMs and sarkosyl with brain homogenates promoted the formation of fibrillar PrP(Sc) aggregates prior to centrifugation, likely through the separation of lipids like GM1 from PrP(Sc). We propose that this separation of lipids from PrP is a major factor governing the facile precipitation of PrP(Sc) by PTA from tissue and might be optimized further for the detection of prions.

Indexed as

AnimalsBlotting, WesternBrainEnzyme-Linked Immunosorbent AssayMicePhosphotungstic AcidPrionsScrapiePhosphotungstic AcidPrions

Identifiers

PMID25695325
PMCPMC4437617
OpenAlexW2031657091

What OpenQuestion holds

Textmetadata
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Registered trials

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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.