TY  - JOUR
AU  - Kardos, Julianna
AU  - Szabó, Zsolt
AU  - Héja, László
TI  - Framing Neuro-Glia Coupling in Antiepileptic Drug Design.
JF  - JOURNAL OF MEDICINAL CHEMISTRY
J2  - J MED CHEM
VL  - 59
PY  - 2016
IS  - 3
SP  - 777
EP  - 787
PG  - 11
SN  - 0022-2623
DO  - 10.1021/acs.jmedchem.5b00331
UR  - https://m2.mtmt.hu/api/publication/2972586
ID  - 2972586
N1  - Funding Agency and Grant Number: TRANS-RAT [KMR_12-1-2012-0112]; ERA Chemistry [NN 102166]
            Funding text: Financial support from Grants KMR_12-1-2012-0112 TRANS-RAT and ERA Chemistry NN 102166 on the "Novel targets and new drug candidates to combat epilepsy: Design of subtype-selective spirobicyclic inhibitors to distinguish among gamma-aminobutyric acid transporter protein subtypes" is greatly acknowledged.
Cited By :13            
            Export Date: 6 April 2021            
            CODEN: JMCMA            
            Correspondence Address: Kardos, J.; Functional Pharmacology Research Group, Hungary; email: kardos.julianna@ttk.mta.hu
Cited By :13            
            Export Date: 7 April 2021            
            CODEN: JMCMA            
            Correspondence Address: Kardos, J.; Functional Pharmacology Research Group, Hungary; email: kardos.julianna@ttk.mta.hu
AB  - 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, gamma-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.
LA  - English
DB  - MTMT
ER  -