The pathological roles of phosphorylation sites, Hsp90 and site-specific mutations in tau aggregation, the roles of CX3CR1/fractalkine signaling in microglia and neurons, the roles of the glutamate-glutamine cycle between astrocyte and neurons in the progression of tau pathologies, and the possible therapeutic role of NLR3 inflammasome in the treatment of tauopathies are the major focus of this review. The gene discussed is CX3CL1; the disease is tauopathy.