Role of Excitatory Amino Acid Carrier 1 (<i>EAAC1</i>) in Neuronal Death and Neurogenesis After Ischemic Stroke
Although there have been substantial advances in knowledge regarding the mechanisms of neuron death after stroke, effective therapeutic measures for stroke are still insufficient. Excitatory amino acid carrier 1 (<i>EAAC1</i>) is a type of neuronal glutamate transporter and considered to...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/16/5676 |
| Summary: | Although there have been substantial advances in knowledge regarding the mechanisms of neuron death after stroke, effective therapeutic measures for stroke are still insufficient. Excitatory amino acid carrier 1 (<i>EAAC1</i>) is a type of neuronal glutamate transporter and considered to have an additional action involving the neuronal uptake of cysteine, which acts as a crucial substrate for glutathione synthesis. Previously, our lab demonstrated that genetic deletion of <i>EAAC1</i> leads to decreased neuronal glutathione synthesis, increased oxidative stress, and subsequent cognitive impairment. Therefore, we hypothesized that reduced neuronal transport of cysteine due to deletion of the <i>EAAC1</i> gene might exacerbate neuronal injury and impair adult neurogenesis in the hippocampus after transient cerebral ischemia. <i>EAAC1</i> gene deletion profoundly increased ischemia-induced neuronal death by decreasing the antioxidant capacity. In addition, genetic deletion of <i>EAAC1</i> also decreased the overall neurogenesis processes, such as cell proliferation, differentiation, and survival, after cerebral ischemia. These studies strongly support our hypothesis that <i>EAAC1</i> is crucial for the survival of newly generated neurons, as well as mature neurons, in both physiological and pathological conditions. Here, we present a comprehensive review of the role of <i>EAAC1</i> in neuronal death and neurogenesis induced by ischemic stroke, focusing on its potential cellular and molecular mechanisms. |
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| ISSN: | 1661-6596 1422-0067 |