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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Role of glutamate excitotoxicity and glutamate transporter EAAT2 in epilepsy: Opportunities for novel therapeutics development
Biochemical pharmacology, v 193, 114786
Nov 2021
PMID: 34571003
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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Epilepsy is a complex neurological syndrome characterized by seizures resulting from neuronal hyperexcitability and sudden and synchronized bursts of electrical discharges. Impaired astrocyte function that results in glutamate excitotoxicity has been recognized to play a key role in the pathogenesis of epilepsy. While there are 26 drugs marketed as anti-epileptic drugs no current treatments are disease modifying as they only suppress seizures rather than the development and progression of epilepsy. Excitatory amino acid transporters (EAATs) are critical for maintaining low extracellular glutamate concentrations and preventing excitotoxicity. When extracellular glutamate concentrations rise to abnormal levels, glutamate receptor overactivation and the subsequent excessive influx of calcium into the post-synaptic neuron can trigger cell death pathways. In this review we discuss targeting EAAT2, the predominant glutamate transporter in the CNS, as a promising approach for developing therapies for epilepsy. EAAT2 upregulation via transcriptional and translational regulation has proven successful in vivo in reducing spontaneous recurrent seizures and offering neuroprotective effects. Another approach to regulate EAAT2 activity is through positive allosteric modulation (PAM). Novel PAMs of EAAT2 have recently been identified and are under development, representing a promising approach for the advance of novel therapeutics for epilepsy.
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Details
- Title
- Role of glutamate excitotoxicity and glutamate transporter EAAT2 in epilepsy: Opportunities for novel therapeutics development
- Creators
- Jennifer Leigh Green - Drexel UniversityWagner Ferreira dos Santos - Universidade de São PauloAndréia Cristina Karklin Fontana - Drexel University
- Publication Details
- Biochemical pharmacology, v 193, 114786
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Accelerated Career Entry Bachelor of Science in Nursing (BSN); Pharmacology and Physiology
- Web of Science ID
- WOS:000704984300004
- Scopus ID
- 2-s2.0-85116112151
- Other Identifier
- 991019312387404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy