Evidence map›Paper›PMID 35012575›Full record

ArticleMolecular neurodegeneration2022

Edaravone activates the GDNF/RET neurotrophic signaling pathway and protects mRNA-induced motor neurons from iPS cells.

Qian Li, Yi Feng, Yingchao Xue, Xiping Zhan, Yi Fu, Gege Gui, Weiqiang Zhou, Jean-Philippe Richard, Arens Taga, Pan Li and 3 more

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

Article in Molecular neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
5.5field-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

22 citing papers in PubMed, 44 citations in OpenAlex.

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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

13 authors at 4 institutions in 2 countries.

Qian LiDepartment of Endocrinology, Key Laboratory of Endocrinology, NHC, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
Yi FengHugo W. Moser Research Institute at Kennedy Krieger, 707 North Broadway, Baltimore, MD, 21205, USA.
Yingchao XueHugo W. Moser Research Institute at Kennedy Krieger, 707 North Broadway, Baltimore, MD, 21205, USA.
Xiping ZhanDepartment of Physiology and Biophysics, Howard University, Washington, DC, 20059, USA.
Yi FuDepartment of Endocrinology, Key Laboratory of Endocrinology, NHC, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
Gege GuiDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
Weiqiang ZhouDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Jean-Philippe RichardDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Arens TagaDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Pan LiDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Xiaobo MaoDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Nicholas J MaragakisDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Mingyao YingHugo W. Moser Research Institute at Kennedy Krieger, 707 North Broadway, Baltimore, MD, 21205, USA. ying@kennedykrieger.org.ORCID 0000-0002-6215-4959
Johns Hopkins University · USKennedy Krieger Institute · USChinese Academy of Medical Sciences & Peking Union Medical College · CNHoward University · US

Funding

Targeting Hyaluronan-mediated Motility Receptor in Glioblastoma Stem CellsR01NS099460 · NINDS · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI YING, MINGYAO · 2017 to 2021
$1.8M
NINDS NIH HHS R01 NS099460
6 · The paper itself

Abstract

backgroundSpinal cord motor neurons (MNs) from human iPS cells (iPSCs) have wide applications in disease modeling and therapeutic development for amyotrophic lateral sclerosis (ALS) and other MN-associated neurodegenerative diseases. We need highly efficient MN differentiation strategies for generating iPSC-derived disease models that closely recapitulate the genetic and phenotypic complexity of ALS. An important application of these models is to understand molecular mechanisms of action of FDA-approved ALS drugs that only show modest clinical efficacy. Novel mechanistic insights will help us design optimal therapeutic strategies together with predictive biomarkers to achieve better efficacy.

methodsWe induce efficient MN differentiation from iPSCs in 4 days using synthetic mRNAs coding two transcription factors (Ngn2 and Olig2) with phosphosite modification. These MNs after extensive characterization were applied in electrophysiological and neurotoxicity assays as well as transcriptomic analysis, to study the neuroprotective effect and molecular mechanisms of edaravone, an FDA-approved drug for ALS, for improving its clinical efficacy.

resultsWe generate highly pure and functional mRNA-induced MNs (miMNs) from control and ALS iPSCs, as well as embryonic stem cells. Edaravone alleviates H

conclusionsThis study provides methodology to facilitate iPSC differentiation and disease modeling. Our discoveries will facilitate the development of optimal edaravone-based therapies for ALS and potentially other neurodegenerative diseases.

Indexed as

Amyotrophic Lateral SclerosisInduced Pluripotent Stem CellsEdaravoneGlial Cell Line-Derived Neurotrophic FactorHumansHydrogen PeroxideMotor NeuronsProto-Oncogene Proteins c-retRNA, MessengerSignal TransductionEdaravoneGlial Cell Line-Derived Neurotrophic FactorHydrogen PeroxideProto-Oncogene Proteins c-retRET protein, humanRNA, MessengerAmyotrophic lateral sclerosisMCI-186Neurotrophic factorSpinal cord motor neuronSynthetic mRNATranscription factor

Identifiers

PMID35012575
PMCPMC8751314
OpenAlexW4226189964

What Socratic 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 Socratic graph.