Evidence map›Paper›PMID 21353660›Full record

ArticleStem cell research2011

Embryonic stem cell-derived motoneurons provide a highly sensitive cell culture model for botulinum neurotoxin studies, with implications for high-throughput drug discovery.

Erkan Kiris, Jonathan E Nuss, James C Burnett, Krishna P Kota, Dawn C Koh, Laura M Wanner, Edna Torres-Melendez, Rick Gussio, Lino Tessarollo, Sina Bavari

Open access · greenAbstract readEvaluation Study
In one paragraph

Article in Stem cell research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

30 citing papers in PubMed, 42 citations in OpenAlex.

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  12. Deubiquitinating enzyme VCIP135 dictates the duration of botulinum neurotoxin type A intoxication.Proceedings of the National Academy of Sciences of the United States of America · 2017
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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

10 authors at 2 institutions in 1 country.

Erkan KirisDepartment of Target Discovery and Experimental Microbiology, US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702-5011, USA.
Jonathan E Nuss
James C Burnett
Krishna P Kota
Dawn C Koh
Laura M Wanner
Edna Torres-Melendez
Rick Gussio
Lino Tessarollo
Sina Bavari
Target (United States) · USNational Cancer Institute · US

Funding

Role of Neurotrophins in the Development of the Mammalian Nervous SystemZIABC010390 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TESSAROLLO, LINO · 2009 to 2025
$14.2M
Role of Trk Receptors in the Development and Function of Non-neuronal StructuresZIABC010391 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TESSAROLLO, LINO · 2009 to 2025
$14.0M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS Z99 CA999999NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

Botulinum neurotoxins (BoNTs) inhibit cholinergic synaptic transmission by specifically cleaving proteins that are crucial for neurotransmitter exocytosis. Due to the lethality of these toxins, there are elevated concerns regarding their possible use as bioterrorism agents. Moreover, their widespread use for cosmetic purposes, and as medical treatments, has increased the potential risk of accidental overdosing and environmental exposure. Hence, there is an urgent need to develop novel modalities to counter BoNT intoxication. Mammalian motoneurons are the main target of BoNTs; however, due to the difficulty and poor efficiency of the procedures required to isolate the cells, they are not suitable for high-throughput drug screening assays. Here, we explored the suitability of embryonic stem (ES) cell-derived motoneurons as a renewable, reproducible, and physiologically relevant system for BoNT studies. We found that the sensitivity of ES-derived motoneurons to BoNT/A intoxication is comparable to that of primary mouse spinal motoneurons. Additionally, we demonstrated that several BoNT/A inhibitors protected SNAP-25, the BoNT/A substrate, in the ES-derived motoneuron system. Furthermore, this system is compatible with immunofluorescence-based high-throughput studies. These data suggest that ES-derived motoneurons provide a highly sensitive system that is amenable to large-scale screenings to rapidly identify and evaluate the biological efficacies of novel therapeutics.

Indexed as

Drug DiscoveryAnimalsBotulinum AntitoxinBotulinum ToxinsCell DifferentiationCells, CulturedDrug Evaluation, PreclinicalEmbryonic Stem CellsHigh-Throughput Screening AssaysMiceMice, Inbred C57BLModels, BiologicalMotor NeuronsSynaptosomal-Associated Protein 25Botulinum AntitoxinBotulinum ToxinsSnap25 protein, mouseSynaptosomal-Associated Protein 25

Identifiers

PMID21353660
PMCPMC3081902
OpenAlexW2088929604

What OpenQuestion holds

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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.