Fig. (1) Schematic representation of the signaling cascade for neuronal degeneration, on the basis of the neuroimmunomodulation theory (12). Activation of microglia is followed by a release of pro-inflammatory mediators that finally promotes tau hypephosphorylation and its aggregation into PHF. Tau release from degenerated neurons triggers microglial reactivation, thus generating a vicious cycle in the pathway to degeneration of neuronal cells in pathological processes like Alzheimer’s disease and tauopathies.