Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia

Abstract

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.

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

“…When considering a neurodevelopmental model of schizophrenia, MIA with LPS has been described in terms of various behavioural disturbances, including affected sensorimotor gating [ 12 , 17 , 18 ], anxiety-like behaviour [ 13 , 19 ], social interactions [ 15 ], exploratory or locomotor activity [ 19 , 20 , 21 ] and cognitive deficits [ 22 , 23 ] as well as diverse biochemical alterations in the brains of the offspring, including the CX3CL1-CX3CR1 and CD200-CD200R pairs, which are crucial in neuron–microglia communication [ 13 , 19 ]. CX3CL1 is a chemokine that differs notably from other representatives of this group in both structure and role [ 24 ], whereas CD200 belongs to a class of surface antigens with immunosuppressive properties [ 25 ]. These ligands are produced mainly by neurons and bind to their corresponding receptors (CX3CR1 and CD200R, respectively) expressed by microglia [ 11 ].…”

Machine learning-based predictive models and drug prediction for schizophrenia in multiple programmed cell death patterns

“…CX3CR1 (40 kDa) is made up of 355 amino acid residues that form an extracellular N-terminus, alternately arranged α-helical domains (TM1-TM7), intracellular (IL1-IL3) and extracellular (EL1-EL3) loops, and an intracellular C-terminus ( Raucci et al, 2014 ). CX3CR1 levels were found downregulated in schizophrenia and may be associated with a depression-anxiety phenotype ( Bergon et al, 2015 ; Chamera et al, 2021 ).…”

CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis

“…The polymorphic residues at positions 249 and 280 may be responsible for dysfunctional CX3CR1 variants, including variants identified in various cancers [108,109]. Polymorphism of CX3CR1 is also related to diseases of the cardiovascular system (e.g., atherosclerosis), nervous system (e.g., Alzheimer's disease) and infections (e.g., systemic candidiasis) [120][121][122][123]. Metabotropic receptors, including CX3CR1, constitute the largest family of cell surface proteins involved in signaling across biological membranes, and conformational changes after ligand attachment are crucial for initiating intracellular signaling pathways [110,117].…”