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Fig. 1 | Future Journal of Pharmaceutical Sciences

Fig. 1

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

Fig. 1

a Neuronal CX3CL1 and microglial CX3CR1 interaction increases proinflammatory cytokines in ischemic brain leading to an increase in ROS and neurodegeneration. CX3CL1–CX3CR1 interaction can also decrease the expression of cytokines and neutrophils following activation of CREB and provide neuroprotection. By contrast, suppression of CREB provides neuroprotection. CX3CL1-CX3CR1 interaction increases arginase-1 and provide neuroprotection. By contrast, inhibition of arginase-1 and 2 prevents stroke in ischemic brain. b CX3CL1-CX3CR1 interaction can increase as well as decrease the expression of cytokines. Increase in cytokines causes neurodegeneration via activation of M1 microglia, whereas a decrease leads to neuroprotection. CX3CL1–CX3CR1 interaction provides neuroprotection via conversion of M1 to M2 microglia. c CX3CL1–CX3CR1 interaction may cause hyperphosphorylation of tau which may lead to neurodegeneration. Increased expression of CX3CL1 prevents tau-CX3CR1 complex formation and tau clearance. CX3CL1–CX3CR1 interaction decreases Aβ deposition. Decreased Aβ deposition occurs via decrease in caspase-3, as a result of an increased expression of CX3CL1. By contrast, increased level of CX3CL1 can decrease TLR4 expression, which leads to a subsequent decrease in the scavenging of Aβ. Deposited Aβ can bind with neuronal CX3CR1 causing neurotoxicity and neurodegeneration. d CX3CL1–CX3CR1 interaction can suppress C/EBPα mediated microglial activation and consequent neurodegeneration. C/EBPα may decrease the expression of proinflammatory cytokines and provide neuroprotection. C/EBPα may increase ROS and produce neurodegeneration. Decreased expression of C/EBPα activates TLR-4 and increases proinflammatory markers causing neurodegeneration. e CX3CL1–CX3CR1 interaction provides neuroprotection by increasing thrombospondins-1 which leads to a decrease in Aβ pathology. By contrast, thrombospondins-1 may increase the expression of post synaptically silent receptors which are linked with neurodegenerative disorders

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