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Current approaches to enhance glutamate transporter function and expression.

Andréia C K Fontana1

  • 1Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.

Journal of Neurochemistry
|June 23, 2015
PubMed
Summary

Targeting excitatory amino acid transporter 2 (EAAT2) offers a promising therapeutic strategy for neurological disorders. Enhancing EAAT2 function or expression may protect against conditions like ALS and Alzheimer's disease.

Keywords:
EAAT2 activatorParawixin1allosteric modulationceftriaxoneexcitotoxicityglutamate transporter

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Area of Science:

  • Neuroscience
  • Neuropharmacology
  • Molecular Biology

Background:

  • L-glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS).
  • Excitatory amino acid transporters (EAATs), particularly EAAT2/GLT-1, regulate extracellular glutamate levels to prevent excitotoxicity.
  • EAAT2 dysfunction is linked to neurological diseases including traumatic brain injury, stroke, ALS, and Alzheimer's disease.

Purpose of the Study:

  • To review the current landscape of EAAT2 activators as a potential therapeutic approach for neurological pathologies.
  • To discuss the challenges and limitations associated with developing EAAT2 activators.

Main Methods:

  • Literature review of studies on EAAT2 activators and their therapeutic potential.
  • Analysis of translational activators (e.g., ceftriaxone, LDN/OSU-0212320) and pharmacological activators of EAAT2.
  • Examination of animal models demonstrating protective effects of EAAT2 modulation.

Main Results:

  • Translational activators of EAAT2 have shown protective effects in animal models of neurodegenerative diseases and epilepsy.
  • Pharmacological activators of EAAT2 activity are emerging as promising neuroprotective agents.
  • Activators targeting EAAT2 function may offer advantages over those enhancing its expression.

Conclusions:

  • Modulating EAAT2 function or expression presents a viable therapeutic strategy for various neurological conditions.
  • Further research into EAAT2 activators is warranted, with a focus on overcoming existing challenges and limitations.
  • EAAT2 activators hold significant potential for neuroprotection and treating glutamate-related excitotoxicity.