Abstract
CX3CL1 (fractalkine) is the only member of the CX3C (delta) subfamily of chemokines which is unique and combines the properties of both chemoattractant and adhesion molecules. The two-form ligand can exist either in a soluble form, like all other chemokines, and as a membrane-anchored molecule. CX3CL1 discloses its biological properties through interaction with one dedicated CX3CR1 receptor which belongs to a family of G protein-coupled receptors (GPCR). The CX3CL1/CX3CR1 axis acts in many physiological phenomena including those occurring in the central nervous system (CNS), by regulating the interactions between neurons, microglia, and immune cells. Apart from the role under physiological conditions, the CX3CL1/CX3CR1 axis was implied to have a role in different neuropathologies such as traumatic brain injury (TBI) and spinal cord injury (SCI). CNS injuries represent a serious public health problem, despite improvements in therapeutic management. To date, no effective treatment has been determined, so they constitute a leading cause of death and severe disability. The course of TBI and SCI has two consecutive poorly demarcated phases: the initial, primary injury and secondary injury. Recent evidence has implicated the role of the CX3CL1/CX3CR1 axis in neuroinflammatory processes occurring after CNS injuries. The importance of the CX3CL1/CX3CR1 axis in the pathophysiology of TBI and SCI in the context of systemic and direct local immune response is still under investigation. This paper, based on a review of the literature, updates and summarizes the current knowledge about CX3CL1/CX3CR1 axis involvement in TBI and SCI pathogenesis, indicating possible molecular and cellular mechanisms with a potential target for therapeutic intervention.
Highlights
Traumatic central nervous system (CNS) injuries are the most heterogeneous as regards the individual response to injury and the results of treatment of the group of diseases
The role of conduction related to the CX3CL1/ CX3CR1 axis, which is analyzed in this paper, has been wellknown in the context of physiological regulation between neurons and microglia, which confirms its position as one of the most important neurochemokines
The general tendency as regards messenger RNA (mRNA) expression indicates that CX3CR1 undergoes regulation to a larger extent than CX3CL1 which seems to be more dependent on the regulation at the post-translational level
Summary
Traumatic central nervous system (CNS) injuries are the most heterogeneous as regards the individual response to injury and the results of treatment of the group of diseases. Ongoing research most commonly concentrates on the mechanisms connected with the inflammatory mediators (e.g., cytokines, including chemokines) secreted by cells located residually in the brain and the spinal cord and by infiltrating CNS structures via blood vessels [52, 53] It seems that the most promising therapeutic direction is the modulation of the inflammatory response by limiting its neurotoxic effect, enhancing the neuroprotective properties and promoting the regeneration of injured neural tissue [54, 55]. This type of dynamic balance facilitates the protection of presynthesized CX3CL1 against premature degradation on the external side of cell membrane and, under appropriate conditions, accelerates the mobility of intracellular content [70, 71] Another form to be described is sCX3CL1 included in 317 amino acid residues, approximately 29 nm long, whose structure encompasses a CD-containing segment and a mucin-like stalk of the total molecular weight of approximately 14.7 kDa, and 80 kDa after glycosylation [59, 60]. They include a significant percentage of immune cell population, i.e., monocytes (CD14+), macrophages (MΦ), NK cells (CD16+), lymphocytes (CD4+ and CD8+), mast cells (MC), and dendritic cells (DC) [105,106,107,108,109]
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