Lennart Bunch1, Mette N Erichsen, Anders A Jensen. 1. Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, Department of Medicinal Chemistry, DK-2100 Copenhagen, Denmark. lebu@farma.ku.dk
Abstract
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.
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.
Authors: Mette N Erichsen; Jeanette Hansen; Josep A Ruiz; Charles S Demmer; Bjarke Abrahamsen; Jesper F Bastlund; Christoffer Bundgaard; Anders A Jensen; Lennart Bunch Journal: Neurochem Res Date: 2014-02-28 Impact factor: 3.996
Authors: Jagadeesh Sridhara Rao; Matthew Kellom; Edmund Arthur Reese; Stanley Isaac Rapoport; Hyung-Wook Kim Journal: J Affect Disord Date: 2011-09-16 Impact factor: 4.839