Evidence map›Paper›PMID 37014877›Full record

ArticlePloS one2023

A seeding-based neuronal model of tau aggregation for use in drug discovery.

Ines S Amorim, Sylvie Challal, Laetitia Cistarelli, Thierry Dorval, Laurene Abjean, Manuelle Touzard, Nicolas Arbez, Arnaud François, Fany Panayi, Ross Jeggo and 5 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Trial
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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

15 authors at 3 institutions in 1 country.

Ines S AmorimSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.ORCID 0000-0002-9911-5064
Sylvie ChallalSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.
Laetitia CistarelliSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.
Thierry DorvalSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.
Laurene AbjeanSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.
Manuelle TouzardSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.
Nicolas ArbezSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.
Arnaud FrançoisSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.
Fany PanayiSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.
Ross JeggoSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.
Erika CeconINSERM, CNRS, Institut Cochin, Université Paris Cité, Paris, France.
Atsuro OishiINSERM, CNRS, Institut Cochin, Université Paris Cité, Paris, France.
Julie DamINSERM, CNRS, Institut Cochin, Université Paris Cité, Paris, France.
Ralf JockersINSERM, CNRS, Institut Cochin, Université Paris Cité, Paris, France.
Patricia MachadoSERVIER, Institut de Recherches Servier, Croissy-sur-Seine, France.
Commissariat à l'Énergie Atomique et aux Énergies Alternatives · FRCentre National de la Recherche Scientifique · FRServier (France) · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intracellular accumulation of tau protein is a hallmark of Alzheimer's Disease and Progressive Supranuclear Palsy, as well as other neurodegenerative disorders collectively known as tauopathies. Despite our increasing understanding of the mechanisms leading to the initiation and progression of tau pathology, the field still lacks appropriate disease models to facilitate drug discovery. Here, we established a novel and modulatable seeding-based neuronal model of full-length 4R tau accumulation using humanized mouse cortical neurons and seeds from P301S human tau transgenic animals. The model shows specific and consistent formation of intraneuronal insoluble full-length 4R tau inclusions, which are positive for known markers of tau pathology (AT8, PHF-1, MC-1), and creates seeding competent tau. The formation of new inclusions can be prevented by treatment with tau siRNA, providing a robust internal control for use in qualifying the assessment of potential therapeutic candidates aimed at reducing the intracellular pool of tau. In addition, the experimental set up and data analysis techniques used provide consistent results in larger-scale designs that required multiple rounds of independent experiments, making this is a versatile and valuable cellular model for fundamental and early pre-clinical research of tau-targeted therapies.

Indexed as

Alzheimer DiseaseTauopathiesAnimalsBrainDrug DiscoveryHumansMiceMice, TransgenicNeuronstau Proteinstau Proteins

Identifiers

PMID37014877
PMCPMC10072482
OpenAlexW4362521199

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.