Evidence map›Paper›PMID 28285880›Full record

ArticleStem cell reports2017

Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer's Disease.

Philip W Brownjohn, James Smith, Erik Portelius, Lutgarde Serneels, Hlin Kvartsberg, Bart De Strooper, Kaj Blennow, Henrik Zetterberg, Frederick J Livesey

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

35 citing papers in PubMed, 67 citations in OpenAlex.

  1. Review
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  9. Automated high-content imaging in iPSC-derived neuronal progenitors.SLAS discovery : advancing life sciences R & D · 2023
    Article
  10. Review
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  14. Review
  15. Phenotyping Neurodegeneration in Human iPSCs.Annual review of biomedical data science · 2021
    Review
  16. Article
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  19. Review
  20. Review
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

9 authors at 4 institutions in 3 countries.

Philip W BrownjohnThe Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge CB2 1QN, UK.
James SmithThe Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge CB2 1QN, UK.
Erik PorteliusDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80 Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 80 Mölndal, Sweden.
Lutgarde SerneelsVIB Center for the Biology of Disease, 3000 Leuven, Belgium; Center for Human Genetics (CME), Leuven Research Institute for Neuroscience and Disease (LIND), University of Leuven (KU Leuven), 3000 Leuven, Belgium.
Hlin KvartsbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80 Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 80 Mölndal, Sweden.
Bart De StrooperVIB Center for the Biology of Disease, 3000 Leuven, Belgium; Center for Human Genetics (CME), Leuven Research Institute for Neuroscience and Disease (LIND), University of Leuven (KU Leuven), 3000 Leuven, Belgium; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80 Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 80 Mölndal, Sweden.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 80 Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 80 Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Frederick J LiveseyThe Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge CB2 1QN, UK. Electronic address: rick@gurdon.cam.ac.uk.
Sahlgrenska University Hospital · SEUniversity of Cambridge · GBVIB-KU Leuven Center for Cancer Biology · BEUniversity of Gothenburg · SE

Funding

European Research Council 681712Medical Research Council MC_PC_17116Medical Research Council MR/L023784/1Medical Research Council MR/L023784/2Wellcome TrustWellcome Trust 101052/2/13/2
6 · The paper itself

Abstract

Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP) processing and the accumulation of APP-derived amyloid β (Aβ) peptides are key processes in Alzheimer's disease (AD). We designed a phenotypic small-molecule screen to identify modulators of APP processing in trisomy 21/Down syndrome neurons, a complex genetic model of AD. We identified the avermectins, commonly used as anthelmintics, as compounds that increase the relative production of short Aβ peptides at the expense of longer, potentially more toxic peptides. Further studies demonstrated that this effect is not due to an interaction with the core γ-secretase responsible for Aβ production. This study demonstrates the feasibility of phenotypic drug screening in human stem cell models of Alzheimer-type dementia, and points to possibilities for indirectly modulating APP processing, independently of γ-secretase modulation.

Indexed as

Alzheimer DiseaseAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnthelminticsCells, CulturedDown SyndromeDrug DiscoveryHumansInduced Pluripotent Stem CellsIvermectinNeurogenesisNeuronsPhenotypeAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnthelminticsavermectinIvermectinAlzheimer's diseaseamyloid betadementiaDown syndromehuman neuronsiPSCsivermectinneural stem cellsphenotypic screeningselamectin

Identifiers

PMID28285880
PMCPMC5390098
OpenAlexW2591588573

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.