ReviewJournal of neurochemistry2015
Main path and byways: non-vesicular glutamate release by system xc(-) as an important modifier of glutamatergic neurotransmission.
Review in Journal of neurochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 102 citations in OpenAlex.
- Sulfur-Containing Amino Acid Homeostasis in the Central Nervous System: From Physiology Regulation to Metal-Induced Neurotoxicity.Metabolites · 2026Review
- Neuroprotective effects of sulfasalazine in experimental model of seizures and epilepsy.BMC neuroscience · 2026Article
- Elucidating the Complex Etiology of Schizophrenia: Comprehensive Insights into the Therapeutic Roles of Natural Compounds and Pharmacological Interventions.Current pharmaceutical design · 2026Review
- Emerging pathological mechanisms of Alzheimer's disease pathogenesis: from neuroimmune interactions to intercellular communication.Frontiers in aging neuroscience · 2026Review
- Intact corticostriatal function in aged system xTranslational psychiatry · 2025Article
- Plasma Cystine as a Marker of Acute Stroke Severity.Diagnostics (Basel, Switzerland) · 2025Article
- Beyond oxidative stress: Ferroptosis as a novel orchestrator in neurodegenerative disorders.Frontiers in immunology · 2025Review
- Decoding ferroptosis in ischemic stroke: key genes and the therapeutic potential of acupuncture.Frontiers in aging neuroscience · 2025Article
- System Xc-pathway as a potential regulatory target in neurological disorders.Frontiers in pharmacology · 2025Review
- Neuropsychiatric Manifestations of COVID-19 Disease and Post COVID Syndrome: The Role of N-acetylcysteine and Acetyl-L-carnitine.Current neuropharmacology · 2025Review
- Aging differentially alters the transcriptome and landscape of chromatin accessibility in the male and female mouse hippocampus.Frontiers in molecular neuroscience · 2024Article
- Review
- Design, synthesis, and characterization of novel system xJournal of neuroinflammation · 2023Article
- N-acetylcysteine Pharmacology and Applications in Rare Diseases-Repurposing an Old Antioxidant.Antioxidants (Basel, Switzerland) · 2023Review
- Critical Roles of the Cysteine-Glutathione Axis in the Production of γ-Glutamyl Peptides in the Nervous System.International journal of molecular sciences · 2023Review
- Loss of functional System x-c uncouples aberrant postnatal neurogenesis from epileptogenesis in the hippocampus of Kcna1-KO mice.Cell reports · 2022Article
- Disruption of Glutamate Homeostasis in the Brain of Rat Offspring Induced by Prenatal and Early Postnatal Exposure to Maternal High-Sugar Diet.Nutrients · 2022Article
- Lifespan extension with preservation of hippocampal function in aged system xMolecular psychiatry · 2022Article
- Ferrostatin-1 alleviates cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis.Bioengineered · 2022Article
- A Breakdown of Immune Tolerance in the Cerebellum.Brain sciences · 2022Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 5 institutions in 4 countries.
Funding
Abstract
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 (Pharmacol. Rev. 64, 2012, 780; Antioxid. Redox Signal. 18, 2013, 522), approached from a different perspective, have recently been published on the functions of system xc(-) in the CNS. 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. System xc(-) constitutes an important source of extrasynaptic glutamate in the brain. By modulating the tone of extrasynaptic metabotropic or ionotropic glutamate receptors, it affects excitatory neurotransmission, the threshold for overexcitation and excitotoxicity and, as a consequence, behavior. This review describes the current knowledge of how system xc(-) is regulated and involved in physiological as well as pathophysiological brain functioning.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.