Abstract
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.
Highlights
Schizophrenia is a chronic brain disease affecting approximately 1% of the world population that causes a severe health burden [1,2]
On the basis of the reviewed studies, we can briefly conclude that some of the candidate genes involved in the neurodevelopment and glutamate-associated signaling that are relevant to schizophrenia, such as D-amino acid oxidase (DAO) and G72 (DAOA), are directly involved in NMDA
Many environmental and epigenetic factors influence the nature of this disease and contribute to the heterogeneous manifestations of schizophrenia [44]
Summary
Schizophrenia is a chronic brain disease affecting approximately 1% of the world population that causes a severe health burden [1,2]. The influence of the aforementioned system xc − on the concentration inside human brain cells was hypothesized to play an important role in the modulation of many neurotransmitter pathways. The neurotransmission glutamate pathway in the brain modulates its activity at multiple ionotropic and metabotropic receptors, assisting its function in human brain plasticity of ensuring learning and memory. In a rodent phencyclidine (PCP) model of schizophrenia, deficits in working memory were reversed by using cystine prodrug N-acetylcysteine pretreatment to enhance and facilitate the activity of system xc − [27] These lines of evidence implicate system xc − in schizophrenia pathogenesis through the regulation of extracellular glutamate and GSH, which can prevent the brain from oxidative damage [31]. The investigation of xc − might lead us to a better understanding of the disease nature of schizophrenia
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
