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  • Huang, Yang ZhongDepartment of Neurobiology, Duke University of Medical Center, Duke University, Durham, NC, United States (författare)

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

  • Artikel/kapitelEngelska2012

Förlag, utgivningsår, omfång ...

  • 2012-06-29
  • Bethesda, United States :American Society for Pharmacology and Experimental Therapeutics,2012
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:liu-143337
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-143337URI
  • https://doi.org/10.1124/mol.112.078220DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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 (KD ∼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. Copyright © 2012 The American Society for Pharmacology and Experimental Therapeutics.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Hernandez, Frank JDepartment of Internal Medicine, University of of Iowa, MERF, 375 Newton Rd., Iowa City, IA 52242, United States(Swepub:liu)frahe49 (författare)
  • Gu, BinDepartment of Pharmacology and Cancer Biology, Duke University of Medical Center, Duke University, Durham, NC, United States (författare)
  • Stockdale, Katie R.Department of Internal Medicine, University of of Iowa, MERF, 375 Newton Rd., Iowa City, IA 52242, United States (författare)
  • Nanapaneni, KishoreCenter for Bioinformatics and Computational Biology, University of of Iowa, Iowa City, IA, United States; Department of Biomedical Engineering, University of of Iowa, Iowa City, IA, United States (författare)
  • Scheetz, Todd E.Center for Bioinformatics and Computational Biology, University of of Iowa, Iowa City, IA, United States; Department of Biomedical Engineering, University of of Iowa, Iowa City, IA, United States; Department of Ophthalmology and Visual Sciences, Roy J. and Lucille A. Carver College of Medicine, University of of Iowa, Iowa City, IA, United States (författare)
  • Behlke, Mark A.Integrated DNA Technologies, Coralville, IA, United States (författare)
  • Peek, Andrew S.Integrated DNA Technologies, Coralville, IA, United States (författare)
  • Bair, ThomasDNA Facility, University of of Iowa, Iowa City, IA, United States (författare)
  • Giangrande, Paloma H.Department of Internal Medicine, University of of Iowa, MERF, 375 Newton Rd., Iowa City, IA 52242, United States (författare)
  • McNamara, James O.Department of Internal Medicine, University of of Iowa, MERF, 375 Newton Rd., Iowa City, IA 52242, United States (författare)
  • Department of Neurobiology, Duke University of Medical Center, Duke University, Durham, NC, United StatesDepartment of Internal Medicine, University of of Iowa, MERF, 375 Newton Rd., Iowa City, IA 52242, United States (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Molecular PharmacologyBethesda, United States : American Society for Pharmacology and Experimental Therapeutics82:4, s. 623-6350026-895X1521-0111

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