Cystine/Glutamate Antiporter in Schizophrenia: From Molecular Mechanism to Novel Biomarker and Treatment
Autor: | Chieh-Hsin Lin, Chung-Chieh Hung, Hsien-Yuan Lane |
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Rok vydání: | 2021 |
Předmět: |
QH301-705.5
Antiporter Glutamic Acid Review Synaptic Transmission cystine/glutamate antiporter Catalysis Antiporters Inorganic Chemistry chemistry.chemical_compound Downregulation and upregulation medicine Animals Humans Biology (General) Physical and Theoretical Chemistry Precision Medicine QD1-999 Molecular Biology Spectroscopy Neurons Neurotransmitter Agents Organic Chemistry Glutamate receptor Disease Management Transporter Biological Transport General Medicine Glutathione Human brain system xc− medicine.disease Computer Science Applications Solute carrier family Cell biology schizophrenia Chemistry Oxidative Stress medicine.anatomical_structure chemistry Schizophrenia Cystine biomarker Disease Susceptibility Biomarkers |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 9718, p 9718 (2021) |
ISSN: | 1422-0067 |
Popis: | Glutamate, a crucial excitatory neurotransmitter, plays a major role in the modulation of schizophrenia’s pathogenesis. New drug developments for schizophrenia have been prompted by the hypoglutamatergic hypothesis of schizophrenia. The cystine/glutamate antiporter system xc− is related to glutamate-release regulation. Patients with schizophrenia were recently discovered to exhibit downregulation of xc− subunits—the solute carrier (SLC) family 3 member 2 and the SLC family 7 member 11. We searched for relevant studies from 1980, when Bannai and Kitamura first identified the protein subunit system xc− in lung fibroblasts, with the aim of compiling the biological, functional, and pharmacological characteristics of antiporter xc−, which consists of several subunits. Some of them can significantly stimulate the human brain through the glutamate pathway. Initially, extracellular cysteine activates neuronal xc−, causing glutamate efflux. Next, excitatory amino acid transporters enhance the unidirectional transportation of glutamate and sodium. These two biochemical pathways are also crucial to the production of glutathione, a protective agent for neural and glial cells and astrocytes. Investigation of the expression of system xc− genes in the peripheral white blood cells of patients with schizophrenia can facilitate better understanding of the mental disorder and future development of novel biomarkers and treatments for schizophrenia. In addition, the findings further support the hypoglutamatergic hypothesis of schizophrenia. |
Databáze: | OpenAIRE |
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