Evidence map›Paper›PMID 34426604›Full record

ArticleScientific reports2021

High-content image-based analysis and proteomic profiling identifies Tau phosphorylation inhibitors in a human iPSC-derived glutamatergic neuronal model of tauopathy.

Chialin Cheng, Surya A Reis, Emily T Adams, Daniel M Fass, Steven P Angus, Timothy J Stuhlmiller, Jared Richardson, Hailey Olafson, Eric T Wang, Debasis Patnaik and 11 more

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

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
4.4field-weighted citation impact, top 4% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Integrative genomic and functional analyses reveal NINL as a modulator of tau aggregation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  12. The Role of Aldose Reductase in Beta-Amyloid-Induced Microglia Activation.International journal of molecular sciences · 2022
    Article
  13. Article
  14. Review
  15. 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

21 authors at 8 institutions in 1 country.

Chialin ChengDepartment of Neurology, Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. ccheng3@mgh.harvard.edu.
Surya A ReisDepartment of Neurology, Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Emily T AdamsDepartment of Neurology, Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Daniel M FassDepartment of Neurology, Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Steven P AngusDepartment of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA.
Timothy J StuhlmillerDepartment of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA.
Jared RichardsonDepartment of Biochemistry & Molecular Biology, Center for NeuroGenetics, University of Florida, Gainesville, FL, 32610, USA.
Hailey OlafsonDepartment of Molecular Genetics & Microbiology, Center for NeuroGenetics, University of Florida, Gainesville, FL, 32610, USA.
Eric T WangDepartment of Molecular Genetics & Microbiology, Center for NeuroGenetics, University of Florida, Gainesville, FL, 32610, USA.
Debasis PatnaikDepartment of Neurology, Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Roberta L BeauchampCenter for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Danielle A FeldmanPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
M Catarina SilvaDepartment of Neurology, Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Mriganka SurPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
Gary L JohnsonDepartment of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA.
Vijaya RameshCenter for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Bruce L MillerDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, CA, 94158, USA.
Sally TempleNeural Stem Cell Institute, Regenerative Research Foundation, Rensselaer, NY, 12144, USA.
Kenneth S KosikDepartment of Molecular, Cellular and Developmental Biology, Neuroscience Research Institute, University of California, Santa Barbara, CA, 93106, USA.
Bradford C DickersonDepartment of Neurology, MGH Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
Stephen J HaggartyDepartment of Neurology, Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. shaggarty@mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · USUniversity of Florida · USUniversity of North Carolina at Chapel Hill · USMassachusetts Institute of Technology · USNeural Stem Cell Institute · USUniversity of California, San Francisco · USUniversity of California, Santa Barbara · US

Funding

Autosomal Dominant FTLD Tauopathy Patient-Specific Stem Cell ModelsR21NS085487 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI DICKERSON, BRADFORD C, HAGGARTY, STEPHEN J · 2014 to 2015
$479k
NINDS NIH HHS R21 NS085487
6 · The paper itself

Abstract

Mutations in MAPT (microtubule-associated protein tau) cause frontotemporal dementia (FTD). MAPT mutations are associated with abnormal tau phosphorylation levels and accumulation of misfolded tau protein that can propagate between neurons ultimately leading to cell death (tauopathy). Recently, a p.A152T tau variant was identified as a risk factor for FTD, Alzheimer's disease, and synucleinopathies. Here we used induced pluripotent stem cells (iPSC) from a patient carrying this p.A152T variant to create a robust, functional cellular assay system for probing pathophysiological tau accumulation and phosphorylation. Using stably transduced iPSC-derived neural progenitor cells engineered to enable inducible expression of the pro-neural transcription factor Neurogenin 2 (Ngn2), we generated disease-relevant, cortical-like glutamatergic neurons in a scalable, high-throughput screening compatible format. Utilizing automated confocal microscopy, and an advanced image-processing pipeline optimized for analysis of morphologically complex human neuronal cultures, we report quantitative, subcellular localization-specific effects of multiple kinase inhibitors on tau, including ones under clinical investigation not previously reported to affect tau phosphorylation. These results demonstrate the potential for using patient iPSC-derived ex vivo models of tauopathy as genetically accurate, disease-relevant systems to probe tau biochemistry and support the discovery of novel therapeutics for tauopathies.

Indexed as

Image Processing, Computer-AssistedModels, BiologicalProteomicsBasic Helix-Loop-Helix ProteinsBiomarkersCell LineGlutamatesHumansInduced Pluripotent Stem CellsNerve Tissue ProteinsNeuronsPhosphorylationProtein KinasesPyridinesPyrimidinesSmall Molecule LibrariesBasic Helix-Loop-Helix ProteinsBiomarkersChir 99021GlutamatesNerve Tissue ProteinsNEUROG2 protein, humanProtein KinasesPyridinesPyrimidinesSmall Molecule Librariestau Proteins

Identifiers

PMID34426604
PMCPMC8382845
OpenAlexW3193304804

What OpenQuestion holds

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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.