Evidence map›Paper›PMID 32179850›Full record

ArticleCommunications biology2020

Transcriptome signature analysis repurposes trifluoperazine for the treatment of fragile X syndrome in mouse model.

Qi Ding, Ferzin Sethna, Xue-Ting Wu, Zhuang Miao, Ping Chen, Yueqi Zhang, Hua Xiao, Wei Feng, Yue Feng, Xuan Li and 1 more

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

8 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. SGLT2 inhibitors prevent LPS-induced M1 macrophage polarization and alleviate inflammatory bowel disease by downregulating NHE1 expression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Article
  4. Targeted Treatments for Fragile X Syndrome.Advances in neurobiology · 2023
    Article
  5. Article
  6. Review
  7. Article
  8. CGG Repeat Expansion, and ElevatedFrontiers in cell and developmental biology · 2020
    Article
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

11 authors at 3 institutions in 2 countries.

Qi Ding *Department of Physiology, Michigan State University, East Lansing, USA.
Ferzin Sethna *Genetics Program, Michigan State University, East Lansing, USA.
Xue-Ting WuKey Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China.
Zhuang MiaoGenetics Program, Michigan State University, East Lansing, USA.
Ping ChenKey Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China.
Yueqi ZhangDepartment of Physiology, Michigan State University, East Lansing, USA.
Hua XiaoDepartment of Physiology, Michigan State University, East Lansing, USA.
Wei FengDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, 30322, Georgia.
Yue FengDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, 30322, Georgia.
Xuan LiKey Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200032, Shanghai, China.
Hongbing WangDepartment of Physiology, Michigan State University, East Lansing, USA. wangho@msu.edu.
Michigan State University · USChinese Academy of Sciences · CNEmory University · US

Funding

Novel Regulation and Function of the lncRNA Gomafu in Human NeuronsR01NS110110 · NINDS · EMORY UNIVERSITY · PI FENG, YUE · 2019 to 2023
$2.9M
Nonconventional role of ADCY in Gq-mediated neuronal signaling and neuroplasticityR01MH119149 · NIMH · MICHIGAN STATE UNIVERSITY · PI WANG, HONGBING · 2019 to 2023
$2.3M
Connecting mGluR and cAMP in the pre-clinical model of Fragile XR01MH093445 · NIMH · MICHIGAN STATE UNIVERSITY · PI WANG, HONGBING · 2012 to 2016
$1.9M
Novel control of CDK5 function in the brainR01NS093016 · NINDS · EMORY UNIVERSITY · PI FENG, YUE · 2015 to 2019
$1.7M
Role of NCOA5 in hepatic steatosis and hepatocarcinogenesisR01CA188305 · NCI · MICHIGAN STATE UNIVERSITY · PI XIAO, HUA · 2015 to 2019
$1.7M
NCI NIH HHS R01 CA188305NIMH NIH HHS R01 MH093445NIMH NIH HHS R01 MH119149NINDS NIH HHS R01 NS093016NINDS NIH HHS R01 NS110110
6 · The paper itself

Abstract

Fragile X syndrome (FXS) is a prevailing genetic disorder of intellectual disability and autism. There is no efficacious medication for FXS. Through in silico screening with a public database, computational analysis of transcriptome profile in FXS mouse neurons predicts therapeutic value of an FDA-approved drug trifluoperazine. Systemic administration of low-dose trifluoperazine at 0.05 mg/kg attenuates multiple FXS- and autism-related behavioral symptoms. Moreover, computational analysis of transcriptome alteration caused by trifluoperazine suggests a new mechanism of action against PI3K (Phosphatidylinositol-4,5-bisphosphate 3-kinase) activity. Consistently, trifluoperazine suppresses PI3K activity and its down-stream targets Akt (protein kinase B) and S6K1 (S6 kinase 1) in neurons. Further, trifluoperazine normalizes the aberrantly elevated activity of Akt and S6K1 and enhanced protein synthesis in FXS mouse. Together, our data demonstrate a promising value of transcriptome-based computation in identification of therapeutic strategy and repurposing drugs for neurological disorders, and suggest trifluoperazine as a potential treatment for FXS.

Indexed as

Drug RepositioningGene Expression ProfilingTranscriptomeAnimalsBehavior, AnimalDisease Models, AnimalFragile X Messenger Ribonucleoprotein 1Fragile X SyndromeHippocampusMaleMice, Inbred C57BLMice, KnockoutNeuronsPhosphotransferases (Alcohol Group Acceptor)Protein Kinase InhibitorsProto-Oncogene Proteins c-aktFmr1 protein, mouseFragile X Messenger Ribonucleoprotein 1phosphatidylinositol 4,5-biphosphate kinasePhosphotransferases (Alcohol Group Acceptor)Protein Kinase InhibitorsProto-Oncogene Proteins c-aktRibosomal Protein S6 Kinases, 90-kDaRps6ka1 protein, mouseTrifluoperazine

Identifiers

PMID32179850
PMCPMC7075969
OpenAlexW3011248070

What OpenQuestion holds

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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.