CX3CL1/CX3CR1 in Alzheimer’s Disease: A Target for Neuroprotection

Figure 1

The effect of CX3CL1/CX3CR1 in Alzheimer’s disease (AD). CX3CL1 binds to CX3CR1 which is its sole receptor and mainly expressed by microglia: (1) regulating introduction of inflammation cytokine (TNF-α, IL-1β, IL-6, NO, etc.) and reducing neuroinflammation in AD; (2) negatively modulating the function of AMPAR and NR2B, increasing GLT activity through the mechanism dependent on A1R, and then decreasing the neurotoxicity induced by Glu; (3) stimulating the release of adenosine; adenosine then activates A2AR and promotes synaptic facilitation by NMDAR-dependent pathway and simultaneity activates A3R and induces synaptic inhibition by Ca²⁺-dependent pathway. TNF-α: tumor necrosis factor-alpha; IL-1β: interleukin-1β; IL-6: interleukin-6; NO: nitric oxide; A1R: adenosine 1 receptor; A2AR: adenosine A2a receptor; A3R: adenosine 3 receptor; GLT: glutamate transporter; LTP: long-term potentiation; CREB: cyclic adenosine monophosphate response element-binding protein; BNDF: brain-derived neurotrophic factor.