Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective
γ-Aminobutyric acid (GABA) Transporters (GATs) belong to sodium and chloride dependent-transporter family and are widely expressed throughout the brain. Notably, GAT1 is accountable for sustaining 75% of the synaptic GABA concentration and entails its transport to the GABAA receptors to initiate the...
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doaj-d3463d689fed4eb19f3f36591bcfcae32020-11-25T01:02:45ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462018-09-01610.3389/fchem.2018.00397360060Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic ProspectiveSadia ZafarIshrat Jabeenγ-Aminobutyric acid (GABA) Transporters (GATs) belong to sodium and chloride dependent-transporter family and are widely expressed throughout the brain. Notably, GAT1 is accountable for sustaining 75% of the synaptic GABA concentration and entails its transport to the GABAA receptors to initiate the receptor-mediated inhibition of post-synaptic neurons. Imbalance in ion homeostasis has been associated with several neurological disorders related to the GABAergic system. However, inhibition of the GABA uptake by these transporters has been accepted as an effective approach to enhance GABAergic inhibitory neurotransmission in the treatment of seizures in epileptic and other neurological disorders. Here, we reviewed computational methodologies including molecular modeling, docking, and molecular dynamic simulations studies to underscore the structure and function of GAT1 in the GABAergic system. Additionally, various SAR and QSAR methodologies have been reviewed to probe the 3D structural features of inhibitors required to modulate GATs activity. Overall, present review provides an overview of crucial role of GAT1 in GABAergic system and its modulation to evade neurological disorders.https://www.frontiersin.org/article/10.3389/fchem.2018.00397/fullγ-aminobutyric acid (GABA)GABA transporters (GATs)homology modelingmolecular dynamics (MD)QSAR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sadia Zafar Ishrat Jabeen |
spellingShingle |
Sadia Zafar Ishrat Jabeen Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective Frontiers in Chemistry γ-aminobutyric acid (GABA) GABA transporters (GATs) homology modeling molecular dynamics (MD) QSAR |
author_facet |
Sadia Zafar Ishrat Jabeen |
author_sort |
Sadia Zafar |
title |
Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective |
title_short |
Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective |
title_full |
Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective |
title_fullStr |
Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective |
title_full_unstemmed |
Structure, Function, and Modulation of γ-Aminobutyric Acid Transporter 1 (GAT1) in Neurological Disorders: A Pharmacoinformatic Prospective |
title_sort |
structure, function, and modulation of γ-aminobutyric acid transporter 1 (gat1) in neurological disorders: a pharmacoinformatic prospective |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Chemistry |
issn |
2296-2646 |
publishDate |
2018-09-01 |
description |
γ-Aminobutyric acid (GABA) Transporters (GATs) belong to sodium and chloride dependent-transporter family and are widely expressed throughout the brain. Notably, GAT1 is accountable for sustaining 75% of the synaptic GABA concentration and entails its transport to the GABAA receptors to initiate the receptor-mediated inhibition of post-synaptic neurons. Imbalance in ion homeostasis has been associated with several neurological disorders related to the GABAergic system. However, inhibition of the GABA uptake by these transporters has been accepted as an effective approach to enhance GABAergic inhibitory neurotransmission in the treatment of seizures in epileptic and other neurological disorders. Here, we reviewed computational methodologies including molecular modeling, docking, and molecular dynamic simulations studies to underscore the structure and function of GAT1 in the GABAergic system. Additionally, various SAR and QSAR methodologies have been reviewed to probe the 3D structural features of inhibitors required to modulate GATs activity. Overall, present review provides an overview of crucial role of GAT1 in GABAergic system and its modulation to evade neurological disorders. |
topic |
γ-aminobutyric acid (GABA) GABA transporters (GATs) homology modeling molecular dynamics (MD) QSAR |
url |
https://www.frontiersin.org/article/10.3389/fchem.2018.00397/full |
work_keys_str_mv |
AT sadiazafar structurefunctionandmodulationofgaminobutyricacidtransporter1gat1inneurologicaldisordersapharmacoinformaticprospective AT ishratjabeen structurefunctionandmodulationofgaminobutyricacidtransporter1gat1inneurologicaldisordersapharmacoinformaticprospective |
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