Framing Neuro-Glia Coupling in Antiepileptic Drug Design

J. Kardos, Zsolt Szabó, László Héja

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We delineate perspectives for the design and discovery of antiepileptic drugs (AEDs) with fewer side effects by focusing on astroglial modulation of spatiotemporal seizure dynamics. It is now recognized that the major inhibitory neurotransmitter of the brain, γ-aminobutyric acid (GABA), can be released through the reversal of astroglial GABA transporters. Synaptic spillover and subsequent glutamate (Glu) uptake in neighboring astrocytes evoke replacement of extracellular Glu for GABA, driving neurons away from the seizure threshold. Attenuation of synaptic signaling by this negative feedback through the interplay of Glu and GABA transporters of adjacent astroglia can result in shortened seizures. By contrast, long-range activation of astroglia through gap junctions may promote recurrent seizures on the model of pharmacoresistant temporal lobe epilepsy. From their first detection to our current understanding, we identify various targets that shape both short- and long-range neuro-astroglia coupling, as these are manifest in epilepsy phenomena and in the associated research promotions of AED.

Original languageEnglish
Pages (from-to)777-787
Number of pages11
JournalJournal of Medicinal Chemistry
Volume59
Issue number3
DOIs
Publication statusPublished - Feb 11 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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