Abstract
Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, which plays an important role in many aspects of normal brain function such as neural development, motor functions, learning and memory etc. However, excessive accumulation of glutamate in the extracellular fluid will induce excitotoxicity which is considered to be a major mechanism of cell death in brain ischemia. There is no enzyme to decompose the glutamate in extracellular fluid, so extracellular glutamate homeostasis within the central nervous system is mainly regulated by the uptake activity of excitatory amino acid transporters. Among the five excitatory amino acid transporters, glial glutamate transporter-1 (GLT-1) is responsible for 90% of total glutamate uptake. Thus, GLT-1 is essential for maintaining the appropriate level of extracellular glutamate, and then limiting excitotoxicity of glutamate in central nervous system. Therefore, the regulation of GLT-1 might be a potential therapeutic target for ischemic brain injury. This review summarizes recent advances including our findings in the methods or medicine that could protect neurons against brain ischemic injury via upregulation of GLT-1 and discuss the possible application of these strategies.
Keywords: Glutamate transporters, GLT-1, brain ischemia, preconditioning, cAMP, estrogen, histamine, dexamethasone, β-lactams antibiotics.
Current Pharmaceutical Design
Title:GLT-1 Upregulation as a Potential Therapeutic Target for Ischemic Brain Injury
Volume: 23 Issue: 33
Author(s): Yu-Yan Hu, Li Li, Xiao-Hui Xian, Min Zhang, Xiao-Cai Sun, Shu-Qin Li, Xin Cui, Jie Qi and Wen-Bin Li*
Affiliation:
- Department of Pathophysiology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017,China
Keywords: Glutamate transporters, GLT-1, brain ischemia, preconditioning, cAMP, estrogen, histamine, dexamethasone, β-lactams antibiotics.
Abstract: Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, which plays an important role in many aspects of normal brain function such as neural development, motor functions, learning and memory etc. However, excessive accumulation of glutamate in the extracellular fluid will induce excitotoxicity which is considered to be a major mechanism of cell death in brain ischemia. There is no enzyme to decompose the glutamate in extracellular fluid, so extracellular glutamate homeostasis within the central nervous system is mainly regulated by the uptake activity of excitatory amino acid transporters. Among the five excitatory amino acid transporters, glial glutamate transporter-1 (GLT-1) is responsible for 90% of total glutamate uptake. Thus, GLT-1 is essential for maintaining the appropriate level of extracellular glutamate, and then limiting excitotoxicity of glutamate in central nervous system. Therefore, the regulation of GLT-1 might be a potential therapeutic target for ischemic brain injury. This review summarizes recent advances including our findings in the methods or medicine that could protect neurons against brain ischemic injury via upregulation of GLT-1 and discuss the possible application of these strategies.
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Cite this article as:
Hu Yu-Yan, Li Li , Xian Xiao-Hui, Zhang Min , Sun Xiao-Cai , Li Shu-Qin, Cui Xin, Qi Jie and Li Wen-Bin *, GLT-1 Upregulation as a Potential Therapeutic Target for Ischemic Brain Injury, Current Pharmaceutical Design 2017; 23 (33) . https://dx.doi.org/10.2174/1381612823666170622103852
DOI https://dx.doi.org/10.2174/1381612823666170622103852 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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