Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan.
Department of Psychiatry, China Medical University Hospital, Taichung 40402, Taiwan.
Int J Mol Sci. 2021 Sep 8;22(18):9718. doi: 10.3390/ijms22189718.
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 x is related to glutamate-release regulation. Patients with schizophrenia were recently discovered to exhibit downregulation of x 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 x in lung fibroblasts, with the aim of compiling the biological, functional, and pharmacological characteristics of antiporter x, which consists of several subunits. Some of them can significantly stimulate the human brain through the glutamate pathway. Initially, extracellular cysteine activates neuronal x, 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 x 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.
谷氨酸是一种至关重要的兴奋性神经递质，在调节精神分裂症发病机制方面发挥着重要作用。精神分裂症的低谷氨酸假说促使了新的药物开发。胱氨酸/谷氨酸反向转运蛋白系统 x 与谷氨酸释放的调节有关。最近发现，精神分裂症患者的 x 亚基（溶质载体 (SLC) 家族 3 成员 2 和 SLC 家族 7 成员 11）表达下调。我们从 1980 年 Bannai 和 Kitamura 首次在肺成纤维细胞中鉴定出蛋白质亚基系统 x 开始搜索相关研究，旨在编译由几个亚基组成的反向转运蛋白 x 的生物学、功能和药理学特征。其中一些亚基可以通过谷氨酸途径显著刺激人类大脑。最初，细胞外半胱氨酸激活神经元 x，导致谷氨酸外排。然后，兴奋性氨基酸转运蛋白增强谷氨酸和钠离子的单向转运。这两种生化途径对于神经和神经胶质细胞以及星形胶质细胞的保护剂谷胱甘肽的产生也至关重要。研究精神分裂症患者外周白细胞中系统 x 基因的表达有助于更好地了解精神障碍，并为精神分裂症的新型生物标志物和治疗方法的开发提供依据。此外，这些发现进一步支持了精神分裂症的低谷氨酸假说。
