Fig. 2
CX3CR1/ Fractalkine signalling—pathophysiological roles in neurons: In neuronal cells, fractalkine plays a significant role in neuroprotection, neurogenesis, learning, memory and synaptic plasticity. The chemokine receptor is involved in Gi-protein-mediated signalling that leads to the activation of the transcription factor, NFκB mediated by PI3K and Akt signals. NFκB is involved in neuronal survival and neuroprotective effects. Fractalkine is also involved in Gi-protein independent activation of ERK kinases that inhibits NMDA receptor-mediated calcium influx and neuronal apoptosis. Fractalkine exposed microglia releases adenosine that is involved in neurotrophic effects via A1 adenosine signalling mechanisms. In neurodegenerative diseases, neurons undergo chronic inflammation, and Tau forms oligomers and filaments due to various post-translational modifications such as phosphorylation. Inflammatory microglia release several pro-inflammatory cytokines such as IL-1β, TNF-α and IL-6. IL-1β promotes Tau phosphorylation and aggregation mediated by IL-1 and TLR-4 receptors. Extracellular Tau interacts with CX3CR1 receptor in microglia for its internalization. We hypothesize that extracellular Tau species may also have possible interaction with neuronal receptor and differential signalling towards neuronal inflammation and neurodegeneration