Excitatory amino acid transporters as potential drug targets

TY - JOUR

T1 - Excitatory amino acid transporters as potential drug targets

AU - Bunch, Lennart

AU - Erichsen, Mette Navy

AU - Jensen, Anders Asbjørn

N1 - Keywords: Central Nervous System; Drug target; EAAT; Glutamate Plasma Membrane Transport Proteins; Humans; Ligands; Models, Molecular; Structure-Activity Relationship; Subtype selectivity; Synapses

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Excitatory amino acid transporters (EAATs) are transmembrane proteins responsible for the uptake of (S)-glutamate (Glu) from the synaptic cleft, thereby terminating the glutamatergic neurotransmitter signal. Today five subtypes have been identified. Except for EAAT2, their individual roles or functions in the CNS are yet to be fully understood due to the shortage of subtype-selective ligands. OBJECTIVE/METHODS: We examine the latest developments in this field by addressing EAAT expression pattern, localization and pharmacology. We present highlights of published work on inhibitors as well as enhancers which display subtype preference or selectivity and discuss which pathological conditions in the CNS such ligands may be beneficial to. RESULTS/CONCLUSIONS: Not until subtype-selective enhancers, inhibitors and substrates for all five EAAT subtypes have been discovered can a full and detailed understanding of EAATs be obtained. Thus we encourage collaboration between organic chemists and molecular pharmacologists, who, together, may pave the way for new EAAT ligands of importance.

AB - BACKGROUND: Excitatory amino acid transporters (EAATs) are transmembrane proteins responsible for the uptake of (S)-glutamate (Glu) from the synaptic cleft, thereby terminating the glutamatergic neurotransmitter signal. Today five subtypes have been identified. Except for EAAT2, their individual roles or functions in the CNS are yet to be fully understood due to the shortage of subtype-selective ligands. OBJECTIVE/METHODS: We examine the latest developments in this field by addressing EAAT expression pattern, localization and pharmacology. We present highlights of published work on inhibitors as well as enhancers which display subtype preference or selectivity and discuss which pathological conditions in the CNS such ligands may be beneficial to. RESULTS/CONCLUSIONS: Not until subtype-selective enhancers, inhibitors and substrates for all five EAAT subtypes have been discovered can a full and detailed understanding of EAATs be obtained. Thus we encourage collaboration between organic chemists and molecular pharmacologists, who, together, may pave the way for new EAAT ligands of importance.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1517/14728220902926127

DO - 10.1517/14728220902926127

M3 - Journal article

C2 - 19456273

SN - 1472-8222

VL - 13

SP - 719

EP - 731

JO - Expert Opinion on Therapeutic Targets

JF - Expert Opinion on Therapeutic Targets

IS - 6

ER -