Thinking Outside the Cleft to Understand Synaptic Activity: Contribution of the Cystine-Glutamate Antiporter (System xc−) to Normal and Pathological Glutamatergic Signaling
| العنوان: | Thinking Outside the Cleft to Understand Synaptic Activity: Contribution of the Cystine-Glutamate Antiporter (System xc−) to Normal and Pathological Glutamatergic Signaling |
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| المؤلفون: | Richard J. Bridges, Doug Lobner, David A. Baker, Victoria Lutgen |
| المصدر: | Pharmacological Reviews. 64:780-802 |
| بيانات النشر: | American Society for Pharmacology & Experimental Therapeutics (ASPET), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Central Nervous System, Amino Acid Transport System y+, Antiporter, Central nervous system, Glutamic Acid, Biology, Reuptake, Glutamatergic, chemistry.chemical_compound, Glutamate homeostasis, medicine, Animals, Humans, Review Articles, Pharmacology, Mental Disorders, Glutamate receptor, Biological Transport, Neurodegenerative Diseases, Glutathione, medicine.anatomical_structure, chemistry, Synapses, Excitatory postsynaptic potential, Cystine, Molecular Medicine, Neurotoxicity Syndromes, Neuroscience, Signal Transduction |
| الوصف: | System x(c)(-) represents an intriguing target in attempts to understand the pathological states of the central nervous system. Also called a cystine-glutamate antiporter, system x(c)(-) typically functions by exchanging one molecule of extracellular cystine for one molecule of intracellular glutamate. Nonvesicular glutamate released during cystine-glutamate exchange activates extrasynaptic glutamate receptors in a manner that shapes synaptic activity and plasticity. These findings contribute to the intriguing possibility that extracellular glutamate is regulated by a complex network of release and reuptake mechanisms, many of which are unique to glutamate and rarely depicted in models of excitatory signaling. Because system x(c)(-) is often expressed on non-neuronal cells, the study of cystine-glutamate exchange may advance the emerging viewpoint that glia are active contributors to information processing in the brain. It is noteworthy that system x(c)(-) is at the interface between excitatory signaling and oxidative stress, because the uptake of cystine that results from cystine-glutamate exchange is critical in maintaining the levels of glutathione, a critical antioxidant. As a result of these dual functions, system x(c)(-) has been implicated in a wide array of central nervous system diseases ranging from addiction to neurodegenerative disorders to schizophrenia. In the current review, we briefly discuss the major cellular components that regulate glutamate homeostasis, including glutamate release by system x(c)(-). This is followed by an in-depth discussion of system x(c)(-) as it relates to glutamate release, cystine transport, and glutathione synthesis. Finally, the role of system x(c)(-) is surveyed across a number of psychiatric and neurodegenerative disorders. |
| تدمد: | 1521-0081 0031-6997 |
| DOI: | 10.1124/pr.110.003889 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4580c2e9f4eaa5a3cb55a304459cd9a0 https://doi.org/10.1124/pr.110.003889 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4580c2e9f4eaa5a3cb55a304459cd9a0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15210081 00316997 |
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| DOI: | 10.1124/pr.110.003889 |