Evidence map›Paper›PMID 37989753›Full record

ArticleNature communications2023

Small molecule regulators of microRNAs identified by high-throughput screen coupled with high-throughput sequencing.

Lien D Nguyen, Zhiyun Wei, M Catarina Silva, Sergio Barberán-Soler, Jiarui Zhang, Rosalia Rabinovsky, Christina R Muratore, Jonathan M S Stricker, Colin Hortman, Tracy L Young-Pearse and 2 more

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

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
11.7field-weighted citation impact, top 1% 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

27 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Lien D Nguyen *Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0001-8096-1570
Zhiyun Wei *Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA. zhiyun_wei@163.com.ORCID 0000-0002-3554-4142
M Catarina SilvaChemical Neurobiology Laboratory, Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.ORCID 0000-0001-5421-6673
Sergio Barberán-SolerRealSeq Biosciences, Santa Cruz, CA, 95060, USA.
Jiarui ZhangDivision of Computational Biomedicine, Boston University School of Medicine, Boston, MA, 02118, USA.
Rosalia RabinovskyDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Christina R MuratoreDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Jonathan M S StrickerDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Colin HortmanRealSeq Biosciences, Santa Cruz, CA, 95060, USA.
Tracy L Young-PearseDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0001-7846-1542
Stephen J HaggartyChemical Neurobiology Laboratory, Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.ORCID 0000-0002-7872-168X
Anna M KrichevskyDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA. akrichevsky@bwh.harvard.edu.ORCID 0000-0002-5080-5507
Brigham and Women's Hospital · USHarvard University · USBoston University · US

Funding

Probing Heterogeneity of Alzheimer's Disease Using iPSCsR01AG055909 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy L YOUNG-PEARSE · 2018 to 2026
$5.7M
miR-SEQ: Highly efficient targeted quantification of extracellular miRNAs by Next Generation SequencingR44GM115124 · NIGMS · SOMAGENICS, INC. · PI BARBERAN-SOLER, SERGIO · 2018 to 2020
$2.0M
Testing miR-132 signaling and replacement as a common strategy for AD, FTD, and related pathologiesR56AG069127 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI KRICHEVSKY, ANNA M. · 2020 to 2020
$844k
NIA NIH HHS R01 AG055909NIA NIH HHS R56 AG069127NIGMS NIH HHS R44 GM115124
6 · The paper itself

Abstract

MicroRNAs (miRNAs) regulate fundamental biological processes by silencing mRNA targets and are dysregulated in many diseases. Therefore, miRNA replacement or inhibition can be harnessed as potential therapeutics. However, existing strategies for miRNA modulation using oligonucleotides and gene therapies are challenging, especially for neurological diseases, and none have yet gained clinical approval. We explore a different approach by screening a biodiverse library of small molecule compounds for their ability to modulate hundreds of miRNAs in human induced pluripotent stem cell-derived neurons. We demonstrate the utility of the screen by identifying cardiac glycosides as potent inducers of miR-132, a key neuroprotective miRNA downregulated in Alzheimer's disease and other tauopathies. Coordinately, cardiac glycosides downregulate known miR-132 targets, including Tau, and protect rodent and human neurons against various toxic insults. More generally, our dataset of 1370 drug-like compounds and their effects on the miRNome provides a valuable resource for further miRNA-based drug discovery.

Indexed as

Cardiac GlycosidesInduced Pluripotent Stem CellsMicroRNAsHigh-Throughput Nucleotide SequencingHumansRNA, MessengerCardiac GlycosidesMicroRNAsRNA, Messenger

Identifiers

PMID37989753
PMCPMC10663445
OpenAlexW4388854107

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.