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Current approaches to enhance glutamate transporter function and expression
Journal article   Open access   Peer reviewed

Current approaches to enhance glutamate transporter function and expression

Andreia C. K. Fontana
Journal of neurochemistry, v 134(6), pp 982-1007
01 Sep 2015
PMID: 26096891
url
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jnc.13200View
Published, Version of Record (VoR) Open
url
https://doi.org/10.1111/jnc.13200View
Published, Version of Record (VoR) Open

Abstract

Biochemistry & Molecular Biology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology
L-glutamate is the predominant excitatory neurotransmitter in the qCNS and has a central role in a variety of brain functions. The termination of glutamate neurotransmission by excitatory amino acid transporters (EAATs) is essential to maintain glutamate concentration low in extracellular space and avoid excitotoxicity. EAAT2/GLT-1, being the most abundant subtype of glutamate transporter in the CNS, plays a key role in regulation of glutamate transmission. Dysfunction of EAAT2 has been correlated with various pathologies such as traumatic brain injury, stroke, amyotrophic lateral sclerosis, Alzheimer's disease, among others. Therefore, activators of the function or enhancers of the expression of EAAT2/GLT-1 could serve as a potential therapy for these conditions. 1Translational activators of EAAT2/GLT-1, such as ceftriaxone and LDN/OSU-0212320, have been described to have significant protective effects in animal models of amyotrophic lateral sclerosis and epilepsy. In addition, pharmacological activators of the activity of EAAT2/GLT-1 have been explored for decades and are currently emerging as promising tools for neuroprotection, having potential advantages over expression activators. This review describes the current status of the search for EAAT2/GLT-1 activators and addresses challenges and limitations that this approach might encounter.

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Web of Science research areas
Biochemistry & Molecular Biology
Neurosciences
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