Implications of fractalkine on glial function, ablation and glial proteins/receptors/markers—understanding its therapeutic usefulness in neurological settings: a narrative review

Abstract

Background Fractalkine (CX3CL1) is a chemokine predominantly released by neurons. As a signaling molecule, CX3CL1 facilitates talk between neurons and glia. CX3CL1 is considered as a potential target which could alleviate neuroinflammation. However, certain controversial results and ambiguous role of CX3CL1 make it inexorable to decipher the overall effects of CX3CL1 on the physiopathology of glial cells. Main body of the abstract Implications of cross-talk between CX3CL1 and different glial proteins/receptors/markers will give a bird eye view of the therapeutic significance of CX3CL1. Keeping with the need, this review identifies the effects of CX3CL1 on glial physiopathology, glial ablation, and gives a wide coverage on the effects of CX3CL1 on certain glial proteins/receptors/markers. Short conclusion Pinpoint prediction of the therapeutic effect of CX3CL1 on neuroinflammation needs further research. This is owing to certain obscure roles and implications of CX3CL1 on different glial proteins/receptors/markers, which are crucial under neurological settings. Further challenges are imposed due to the dichotomous roles played by CX3CL1. The age-old chemokine shows many newer scopes of research in near future. Thus, overall assessment of the effect of CX3CL1 becomes crucial prior to its administration in neuroinflammation.

Microglia regulate motor neuron plasticity via reciprocal fractalkine/adenosine signaling

“…Previous studies indicate neuron-microglial Fkn signaling regulates important neural functions such as hippocampal synaptic plasticity 7,8 and medullary respiratory rhythm generation 9 . Fractalkine modulates activity-dependent synaptic transmission via factors such as microglia-dependent increases in extracellular ATP and/or adenosine 3,10,11 . However, the role of microglia in regulating any form of spinal, motor or activity-independent synaptic plasticity is unknown.…”

Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain

“…This chemokine is produced by neurons in the spinal cord and DRGs after nerve injury, while its receptor, CX3CR1, is present on the surface of microglial cells and is highly upregulated during neuropathic pain development [8]. It is also known that the binding of CX3CR1 by CX3CL1 increases microglial proliferation and migration [197,198]. There is also evidence that ERK5, which is expressed by microglia, is necessary for CX3CL1/CX3CR1-induced microglial activation and the induction of hyperalgesia [199].…”