Neuroprotective properties of the excitatory amino acid carrier 1 (EAAC1)
- PMID: 23462929
- DOI: 10.1007/s00726-013-1481-5
Neuroprotective properties of the excitatory amino acid carrier 1 (EAAC1)
Abstract
Extracellular glutamate should be maintained at low levels to conserve optimal neurotransmission and prevent glutamate neurotoxicity in the brain. Excitatory amino acid transporters (EAATs) play a pivotal role in removing extracellular glutamate in the central nervous system (CNS). Excitatory amino acid carrier 1 (EAAC1) is a high-affinity Na⁺-dependent neuronal EAAT that is ubiquitously expressed in the brain. However, most glutamate released in the synapses is cleared by glial EAATs, but not by EAAC1 in vivo. In the CNS, EAAC1 is widely distributed in somata and dendrites but not in synaptic terminals. The contribution of EAAC1 to the control of extracellular glutamate levels seems to be negligible in the brain. However, EAAC1 can transport not only extracellular glutamate but also cysteine into the neurons. Cysteine is an important substrate for glutathione (GSH) synthesis in the brain. GSH has a variety of neuroprotective functions, while its depletion induces neurodegeneration. Therefore, EAAC1 might exert a critical role for neuroprotection in neuronal GSH metabolism rather than glutamatergic neurotransmission, while EAAC1 dysfunction would cause neurodegeneration. Despite the potential importance of EAAC1 in the brain, previous studies have mainly focused on the glutamate neurotoxicity induced by glial EAAT dysfunction. In recent years, however, several studies have revealed regulatory mechanisms of EAAC1 functions in the brain. This review will summarize the latest information on the EAAC1-regulated neuroprotective functions in the CNS.
Similar articles
-
Regulation of neuronal glutathione synthesis.J Pharmacol Sci. 2008 Nov;108(3):227-38. doi: 10.1254/jphs.08r01cr. Epub 2008 Nov 13. J Pharmacol Sci. 2008. PMID: 19008644 Review.
-
Modulation of neuronal glutathione synthesis by EAAC1 and its interacting protein GTRAP3-18.Amino Acids. 2012 Jan;42(1):163-9. doi: 10.1007/s00726-011-0861-y. Epub 2011 Mar 5. Amino Acids. 2012. PMID: 21373771 Review.
-
Transport of L-[14C]cystine and L-[14C]cysteine by subtypes of high affinity glutamate transporters over-expressed in HEK cells.Neurochem Int. 2005 Jun;46(8):585-94. doi: 10.1016/j.neuint.2005.03.001. Epub 2005 Apr 12. Neurochem Int. 2005. PMID: 15863236
-
Comparison of Na+-dependent glutamate transport activity in synaptosomes, C6 glioma, and Xenopus oocytes expressing excitatory amino acid carrier 1 (EAAC1).Mol Pharmacol. 1996 Mar;49(3):465-73. Mol Pharmacol. 1996. PMID: 8643086
-
Excitatory amino acid transporter expression by astrocytes is neuroprotective against microglial excitotoxicity.Brain Res. 2008 May 19;1210:11-9. doi: 10.1016/j.brainres.2008.03.012. Epub 2008 Mar 20. Brain Res. 2008. PMID: 18410911
Cited by
-
Reversibility of Age-related Oxidized Free NADH Redox States in Alzheimer's Disease Neurons by Imposed External Cys/CySS Redox Shifts.Sci Rep. 2019 Aug 2;9(1):11274. doi: 10.1038/s41598-019-47582-x. Sci Rep. 2019. PMID: 31375701 Free PMC article.
-
Reduced Slc1a1 expression is associated with neuroinflammation and impaired sensorimotor gating and cognitive performance in mice: Implications for schizophrenia.PLoS One. 2017 Sep 8;12(9):e0183854. doi: 10.1371/journal.pone.0183854. eCollection 2017. PLoS One. 2017. PMID: 28886095 Free PMC article.
-
Genetic deletion of the neuronal glutamate transporter, EAAC1, results in decreased neuronal death after pilocarpine-induced status epilepticus.Neurochem Int. 2014 Jul;73:152-8. doi: 10.1016/j.neuint.2013.11.013. Epub 2013 Dec 12. Neurochem Int. 2014. PMID: 24334055 Free PMC article.
-
Differential effects of N-acetylcysteine on retinal degeneration in two mouse models of normal tension glaucoma.Cell Death Dis. 2019 Jan 28;10(2):75. doi: 10.1038/s41419-019-1365-z. Cell Death Dis. 2019. PMID: 30692515 Free PMC article.
-
An Update on Glutathione's Biosynthesis, Metabolism, Functions, and Medicinal Purposes.Curr Med Chem. 2024;31(29):4579-4601. doi: 10.2174/0109298673251025230919105818. Curr Med Chem. 2024. PMID: 37921175 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources