ReviewPharmacological reviews2012
Thinking outside the cleft to understand synaptic activity: contribution of the cystine-glutamate antiporter (System xc-) to normal and pathological glutamatergic signaling.
Review in Pharmacological reviews, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
What it found
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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
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.
- Ferroptosis and ferritinophagy in diabetes complications.Molecular metabolism · 2022Pooled it
- The SLC7A11 Thermostat: A Molecular Signaling Switch Between Ferroptosis and Disulfidptosis in Neurodegenerative Disease.Molecular neurobiology · 2026Review
- Benzothiazole Derivatives as Dual Modulators of PGE2 and GABAergic Signaling in Skeletal Muscle.bioRxiv : the preprint server for biology · 2026Article
- Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors.Molecular psychiatry · 2026Article
- An Overview of Depression Pathogenesis: Prevailing Hypotheses and Associated Neurobiological Underpinnings Primarily Evidenced by Rodent Studies.Depression and anxiety · 2026Review
- Traumatic brain injury-related ferroptosis: current perspectives.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Progress in research on the mechanisms and therapeutic strategies of SLC7A11 regulation in glioma.Discover oncology · 2025Review
- Irisin ameliorates age-associated skeletal muscle atrophy in mice: potential involvement of iron overload and SIRT1/p53 pathway.Journal of physiology and biochemistry · 2025Article
- Hydrogen sulfide/polysulfides signaling and neuronal diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Changes in Redox Balance and Mitochondrial Activity in the Retinas of Cystine/Glutamate Antiporter Knockout Mice.Investigative ophthalmology & visual science · 2025Article
- The Crosstalk Between Ferritinophagy and Ferroptosis in Ischemic Stroke: Regulatory Mechanisms and Therapeutic Implications.Cellular and molecular neurobiology · 2025Review
- Fluoride Exposure Increases the Activity of the Cystine/Glutamate Exchanger in Glia Cells.Neurochemical research · 2025Article
- Exploring the utility of N-acetylcysteine for loss of control eating: protocol of an open-label single-arm pilot study.Pilot and feasibility studies · 2025Article
- Environmental enrichment and sex, but not n-acetylcysteine, alter extended-access amphetamine self-administration and cue-seeking.Behavioural brain research · 2025Article
- Ferroptosis in central nervous system injuries: molecular mechanisms, diagnostic approaches, and therapeutic strategies.Frontiers in cellular neuroscience · 2025Review
- The Mechanism and Inflammatory Markers Involved in the Potential Use of N-acetylcysteine in Chronic Pain Management.Life (Basel, Switzerland) · 2024Review
- Lysine 473 Regulates the Progression of SLC7A11, the Cystine/Glutamate Exchanger, through the Secretory Pathway.International journal of molecular sciences · 2024Article
- Interference with glutamate antiporter system xExperimental physiology · 2024Article
- Ferritinophagy and Ferroptosis in Cerebral Ischemia Reperfusion Injury.Neurochemical research · 2024Review
- Recent advances in potential therapeutic targets of ferroptosis‑associated pathways for the treatment of stroke (Review).Molecular medicine reports · 2024Review
68 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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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.