Selective aptamer-based control of intraneuronal signaling

Angew Chem Int Ed Engl. 2015 Apr 27;54(18):5369-73. doi: 10.1002/anie.201409597. Epub 2015 Mar 5.

Abstract

Cellular behavior is orchestrated by the complex interactions of a myriad of intracellular signal transduction pathways. To understand and investigate the role of individual components in such signaling networks, the availability of specific inhibitors is of paramount importance. We report the generation and validation of a novel variant of an RNA aptamer that selectively inhibits the mitogen-activated kinase pathway in neurons. We demonstrate that the aptamer retains function under intracellular conditions and that application of the aptamer through the patch-clamp pipette efficiently inhibits mitogen-activated kinase-dependent synaptic plasticity. This approach introduces synthetic aptamers as generic tools, readily applicable to inhibit different components of intraneuronal signaling networks with utmost specificity.

Keywords: MAP kinase; SELEX; aptamers; neurosciences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / pharmacology*
  • CA1 Region, Hippocampal / drug effects*
  • CA1 Region, Hippocampal / enzymology
  • In Vitro Techniques
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neuronal Plasticity / drug effects
  • Neurons / drug effects*
  • Neurons / enzymology
  • Patch-Clamp Techniques
  • Synaptic Potentials / drug effects

Substances

  • Aptamers, Nucleotide
  • Mitogen-Activated Protein Kinases