Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St., 31-343, Kraków, Poland.
Pharmacol Rep. 2021 Aug;73(4):1063-1078. doi: 10.1007/s43440-021-00269-5. Epub 2021 May 22.
Schizophrenia has a complex and heterogeneous molecular and clinical picture. Over the years of research on this disease, many factors have been suggested to contribute to its pathogenesis. Recently, the inflammatory processes have gained particular interest in the context of schizophrenia due to the increasing evidence from epidemiological, clinical and experimental studies. Within the immunological component, special attention has been brought to chemokines and their receptors. Among them, CX3C chemokine receptor 1 (CX3CR1), which belongs to the family of seven-transmembrane G protein-coupled receptors, and its cognate ligand (CX3CL1) constitute a unique system in the central nervous system. In the view of regulation of the brain homeostasis through immune response, as well as control of microglia reactivity, the CX3CL1-CX3CR1 system may represent an attractive target for further research and schizophrenia treatment. In the review, we described the general characteristics of the CX3CL1-CX3CR1 axis and the involvement of this signaling pathway in the physiological processes whose disruptions are reported to participate in mechanisms underlying schizophrenia. Furthermore, based on the available clinical and experimental data, we presented a guide to understanding the implication of the CX3CL1-CX3CR1 dysfunctions in the course of schizophrenia.
精神分裂症具有复杂且异质的分子和临床特征。多年来,针对这种疾病的研究提出了许多可能导致其发病的因素。最近,由于流行病学、临床和实验研究的证据不断增加,炎症过程在精神分裂症的背景下引起了特别关注。在免疫成分中,趋化因子及其受体受到了特别关注。其中,属于七跨膜 G 蛋白偶联受体家族的 CX3C 趋化因子受体 1 (CX3CR1)及其同源配体 (CX3CL1)在中枢神经系统中构成了一个独特的系统。鉴于其通过免疫反应调节大脑内稳态以及控制小胶质细胞反应的能力,CX3CL1-CX3CR1 系统可能成为进一步研究和治疗精神分裂症的有吸引力的靶点。在综述中,我们描述了 CX3CL1-CX3CR1 轴的一般特征,以及该信号通路在生理过程中的参与,据报道,这些生理过程的中断参与了精神分裂症发病机制的研究。此外,基于现有的临床和实验数据,我们提供了一份指南,以帮助理解 CX3CL1-CX3CR1 功能障碍在精神分裂症病程中的意义。