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Cited by 170Amino Acid Enzymes and MetabolismNeuroscience and Neuropharmacology ResearchSulfur Compounds in Biology

Excitatory Amino Acid Transporters in Physiology and Disorders of the Central Nervous System

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Malik, Anna R., Willnow, Thomas E.·2019·International Journal of Molecular Sciences
DOI 10.3390/ijms20225671PMC PMC6888459
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Abstract

Excitatory amino acid transporters (EAATs) encompass a class of five transporters with distinct expression in neurons and glia of the central nervous system (CNS). EAATs are mainly recognized for their role in uptake of the amino acid glutamate, the major excitatory neurotransmitter. EAATs-mediated clearance of glutamate released by neurons is vital to maintain proper glutamatergic signalling and to prevent toxic accumulation of this amino acid in the extracellular space. In addition, some EAATs also act as chloride channels or mediate the uptake of cysteine, required to produce the reactive oxygen speciesscavenger glutathione. Given their central role in glutamate homeostasis in the brain, as well as their additional activities, it comes as no surprise that EAAT dysfunctions have been implicated in numerous acute or chronic diseases of the CNS, including ischemic stroke and epilepsy, cerebellar ataxias, amyotrophic lateral sclerosis, Alzheimer’s disease and Huntington’s disease. Here we review the studies in cellular and animal models, as well as in humans that highlight the roles of EAATs in the pathogenesis of these devastating disorders. We also discuss the mechanisms regulating EAATs expression and intracellular trafficking and new exciting possibilities to modulate EAATs and to provide neuroprotection in course of pathologies affecting the CNS.

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  • The subcellular localization of GLAST is typically perisynaptic, and it is highly mobile within the astrocyte membrane influenced by neuronal and glial activity.

    “the subcellular localization of GLAST is typically perisynaptic, it is highly mobile within the astrocyte membrane influenced by neuronal and glial activity [120].”

    From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [120]

    The Introduction identifies GLAST as EAAT1, and Section 3 describes EAAT1 as prominently perisynaptic. Section 6 says that EAAT2—not GLAST/EAAT1—is highly mobile on astrocyte surfaces, with mobility affected by neuronal and glial activity. The mobility portion therefore is not supported for GLAST. (LLM, conf=0.90)

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200 of 281 shown

Authors
Malik, A. R., & Willnow, T. E.
Affiliations
  • Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
  • Max Delbrück Center (DE)
Corresponding author
Malik, Anna R.
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2019-11-12
Volume
20
Issue
22
Pages
5671
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms20225671
PMC
PMC6888459
OpenAlex
W2986012156
Cited by
170
References
300
Citations by year
2026: 10 · 2025: 34 · 2024: 33 · 2023: 21 · 2022: 32 · 2021: 18 · 2020: 21 · 2019: 1
FWCI
1.97
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
Funders
  • Fundacja na rzecz Nauki Polskiej (POIR.04.04.00 00 5CEF/18 00)
  • European Research Council (335692)
  • Helmholtz Association (AMPro)
  • Alzheimer Forschung Initiative (18003)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Keywords
glutamate transporters, glutamate uptake, glutamate homeostasis, glutamatergic signalling, ischemic stroke, epilepsy, cerebellar ataxia, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, glutathione, cysteine uptake, neuroprotection, central nervous system disorders
MeSH terms
Animals, Biological Transport, Brain Diseases, Central Nervous System, Humans, Synaptic Transmission, Neurons, Glutamate Plasma Membrane Transport Proteins

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