Evidence map›Paper›PMID 32034092›Full record

ArticleThe Journal of biological chemistry2020

Compound screening in cell-based models of tau inclusion formation: Comparison of primary neuron and HEK293 cell assays.

Alex Crowe, Mark J Henderson, Johnathon Anderson, Steven A Titus, Alexey Zakharov, Anton Simeonov, Arjan Buist, Charlotte Delay, Diederik Moechars, John Q Trojanowski and 2 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

14 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. HDAC6 Inhibition Reduces Seeded Tau and α-Synuclein Pathologies in Primary Neuron Cultures and Wild-Type Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  4. Article
  5. Review
  6. Targeting Endogenous Tau in Seeded Tauopathy Models Inhibits Tau Spread.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. UsingFrontiers in pharmacology · 2022
    Review
  14. 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

12 authors at 3 institutions in 2 countries.

Alex CroweCenter for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Mark J HendersonNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850.ORCID 0000-0001-8590-7338
Johnathon AndersonCenter for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Steven A TitusNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850.
Alexey ZakharovNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850.
Anton SimeonovNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850.
Arjan BuistDepartment of Neuroscience, Janssen Research and Development, Janssen Pharmaceutica NV, B-2340 Beerse, Belgium.
Charlotte DelayDepartment of Neuroscience, Janssen Research and Development, Janssen Pharmaceutica NV, B-2340 Beerse, Belgium.
Diederik MoecharsDepartment of Neuroscience, Janssen Research and Development, Janssen Pharmaceutica NV, B-2340 Beerse, Belgium.
John Q TrojanowskiCenter for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Virginia M-Y LeeCenter for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Kurt R BrundenCenter for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 kbrunden@upenn.edu.ORCID 0000-0002-9732-134X
University of Pennsylvania · USNational Institutes of Health · USJanssen (Belgium) · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The hallmark pathological features of Alzheimer's disease (AD) brains are senile plaques, comprising β-amyloid (Aβ) peptides, and neuronal inclusions formed from tau protein. These plaques form 10-20 years before AD symptom onset, whereas robust tau pathology is more closely associated with symptoms and correlates with cognitive status. This temporal sequence of AD pathology development, coupled with repeated clinical failures of Aβ-directed drugs, suggests that molecules that reduce tau inclusions have therapeutic potential. Few tau-directed drugs are presently in clinical testing, in part because of the difficulty in identifying molecules that reduce tau inclusions. We describe here two cell-based assays of tau inclusion formation that we employed to screen for compounds that inhibit tau pathology: a HEK293 cell-based tau overexpression assay, and a primary rat cortical neuron assay with physiological tau expression. Screening a collection of ∼3500 pharmaceutical compounds with the HEK293 cell tau aggregation assay, we obtained only a low number of hit compounds. Moreover, these compounds generally failed to inhibit tau inclusion formation in the cortical neuron assay. We then screened the Prestwick library of mostly approved drugs in the cortical neuron assay, leading to the identification of a greater number of tau inclusion inhibitors. These included four dopamine D2 receptor antagonists, with D2 receptors having previously been suggested to regulate tau inclusions in a

Indexed as

Alzheimer DiseaseAnimalsDopamine D2 Receptor AntagonistsHEK293 CellsHumansMiceMicroscopy, FluorescenceNeuronsProtein AggregatesRatsSmall Molecule Librariestau ProteinsDopamine D2 Receptor AntagonistsProtein AggregatesSmall Molecule Librariestau ProteinsaggregationAlzheimer diseaseamyloid plaquedrug discoverydrug screeninginhibitorneurodegenerationneurotoxicitytau protein (tau)

Identifiers

PMID32034092
PMCPMC7086036
OpenAlexW3005011615

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.