Main path and byways: non-vesicular glutamate release by system xc(-) as an important modifier of glutamatergic neurotransmission.
Main path and byways: non-vesicular glutamate release by system xc(-) as an important modifier of glutamatergic neurotransmission.
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DOI：
10.1111/jnc.13348
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发表时间：
2015-12
影响因子：
4.7
通讯作者：
Lewerenz J
中科院分区：
文献类型：
--
作者：
Massie A;Boillée S;Hewett S;Knackstedt L;Lewerenz J
System xc− is a cystine/glutamate antiporter that exchanges extracellular cystine for intracellular glutamate. Cystine is intracellularly reduced to cysteine, a building block of GSH. As such, system xc− can regulate the antioxidant capacity of cells. Moreover, in several brain regions, system xc− is the major source of extracellular glutamate. As such this antiporter is able to fulfill key physiological functions in the CNS, while evidence indicates it also plays a role in certain brain pathologies. Since the transcription of xCT, the specific subunit of system xc−, is enhanced by the presence of reactive oxygen species and inflammatory cytokines, system xc− could be involved in toxic extracellular glutamate release in neurological disorders that are associated with increased oxidative stress and neuroinflammation. System xc− has also been reported to contribute to the invasiveness of brain tumors and, as a source of extracellular glutamate, could participate in the induction of peritumoral seizures. Two independent reviews, approached from a different perspective, have recently been published on the functions of system xc− in the central nervous system. In this review, we highlight novel achievements and insights covering the regulation of system xc− as well as its involvement in emotional behavior, cognition, addiction, neurological disorders and glioblastomas, acquired in the past few years.
