Fig. 6

Schematic diagram of dopamine as a countersignal to α-syn-mediated NLRP3 inflammasome activation in PD. Fibrillar α-syn is taken up by microglia, leading to K⁺ efflux-dependent activation of the NLRP3 inflammasome. The efflux of K⁺ could affect the Kv1.3-mediated or toxicity-induced release of DA from proximal dopaminergic neurons. DA can then bind to microglial DRDs to curb activation of the inflammasome. Sufficient DA in the system would keep this interaction under control, but if DA is depleted over time by the microglia, the imbalance could allow for the progression of neurotoxicity and inflammation