Evidence map›Paper›PMID 22752556›Full record

ArticleMolecular pharmacology2012

RNA aptamer-based functional ligands of the neurotrophin receptor, TrkB.

Yang Zhong Huang, Frank J Hernandez, Bin Gu, Katie R Stockdale, Kishore Nanapaneni, Todd E Scheetz, Mark A Behlke, Andrew S Peek, Thomas Bair, Paloma H Giangrande and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

21 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Porous Silicon Nanoparticles Embedded in Poly(lactic-Advanced functional materials · 2020
    Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Cellular Delivery of RNA Nanoparticles.ACS combinatorial science · 2016
    Review
  13. Article
  14. Article
  15. Aptamer Selection Technology and Recent Advances.Molecular therapy. Nucleic acids · 2015
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
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 4 institutions in 1 country.

Yang Zhong HuangDepartment of Neurobiology, Duke University Medical Center, Duke University, Durham, North Carolina, USA.
Frank J Hernandez
Bin Gu
Katie R Stockdale
Kishore Nanapaneni
Todd E Scheetz
Mark A Behlke
Andrew S Peek
Thomas Bair
Paloma H Giangrande
James O McNamara
University of Iowa · USDuke University Hospital · USDuke University · USDuke Medical Center · US

Funding

Neurotrophins and EpileptogenesisR01NS056217 · NINDS · DUKE UNIVERSITY · PI MCNAMARA, JAMES O. · 2006 to 2023
$6.7M
Aptamer-siRNA Chimeras Targeting HER2-Positive Breast CancersR01CA138503 · NCI · UNIVERSITY OF IOWA · PI GIANGRANDE, PALOMA HOBAN · 2009 to 2013
$1.5M
NCI NIH HHS R01 CA138503NINDS NIH HHS NS056217NINDS NIH HHS R01 NS056217
6 · The paper itself

Abstract

Many cell surface signaling receptors, such as the neurotrophin receptor, TrkB, have emerged as potential therapeutic targets for diverse diseases. Reduced activation of TrkB in particular is thought to contribute to neurodegenerative diseases. Unfortunately, development of therapeutic reagents that selectively activate particular cell surface receptors such as TrkB has proven challenging. Like many cell surface signaling receptors, TrkB is internalized upon activation; in this proof-of-concept study, we exploited this fact to isolate a pool of nuclease-stabilized RNA aptamers enriched for TrkB agonists. One of the selected aptamers, C4-3, was characterized with recombinant protein-binding assays, cell-based signaling and functional assays, and, in vivo in a seizure model in mice. C4-3 binds the extracellular domain of TrkB with high affinity (K(D) ∼2 nM) and exhibits potent TrkB partial agonistic activity and neuroprotective effects in cultured cortical neurons. In mice, C4-3 activates TrkB upon infusion into the hippocampus; systemic administration of C4-3 potentiates kainic acid-induced seizure development. We conclude that C4-3 is a potentially useful therapeutic agent for neurodegenerative diseases in which reduced TrkB activation has been implicated. We anticipate that the cell-based aptamer selection approach used here will be broadly applicable to the identification of aptamer-based agonists for a variety of cell-surface signaling receptors.

Indexed as

AnimalsAnticonvulsantsAptamers, NucleotideBrain-Derived Neurotrophic FactorCells, CulturedHigh-Throughput Nucleotide SequencingHippocampusLigandsMaleMiceMice, Inbred C57BLModels, MolecularNeuronsNeuroprotective AgentsNucleic Acid ConformationProtein BindingAnticonvulsantsAptamers, NucleotideBrain-Derived Neurotrophic FactorLigandsNeuroprotective AgentsReceptor, trkB

Identifiers

PMID22752556
PMCPMC3463223
OpenAlexW2134603426

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.