Abstract
AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels. Excessive activity of AMPA and kainate receptors has been implicated in neurological diseases, such as epilepsy and neuropathic pain. Antagonists that block their activities are therefore potential drug candidates. In a recent article in the Journal of Biological Chemistry by Jaremko et al. 2017, we have reported on the discovery and molecular characterization of an RNA aptamer of a dual functionality: the full-length RNA (101 nucleotide) inhibits AMPA receptors while the truncated or the short (55 nucleotide) RNA inhibits both the AMPA and kainate receptors. The full-length RNA aptamer was isolated through a specially designed, systematic evolution of ligands by exponential enrichment (SELEX) using only a single type of AMPA receptors expressed in HEK-293 cells. The design feature and the results of our recent article are highlighted here, as they demonstrate the utility of the SELEX approach and the potential of using a single AMPA receptor type to develop potent, novel RNA aptamers targeting multiple subunits and AMPA/kainate receptor subtypes with length-dependent functionalities.
Highlights
AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels
In a recent article in the Journal of Biological Chemistry by Jaremko et al 2017[8], we have reported such an approach for the discovery and molecular characterization of an RNA aptamer that has a length-dependent, dual functionality against AMPA and kainate receptors
A study of GluK2deficient mice has revealed that hippocampal neurons in the CA3 region express both AMPA and kainate receptors, and both receptor types are involved in seizures [15]
Summary
AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels. Keywords AMPA receptors; kainate receptors; SELEX; RNA aptamers
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