FIGURE 8.

Vicious cycle of dopamine deficiency, aging, inflammation, and CNS disease. Schematic illustration of the interacting harmful cascades arising from DA deficiency at central and peripheral levels engendering a detrimental vicious cycle. The dramatic loss of DA‐mediated signaling at central and peripheral levels associated with the age‐ and PD‐dependent GSK‐3β overactivation in turn creates a favorable milieu driving a feedforward cycle of inflammation/neurodegeneration, as loss of Nrf2/Wnt and upregulation of GSK‐3 phosphorylating and degrading β‐catenin further drive inflammation and excessive oxidative stress associated with inhibition of adult neurogenesis and neurorepair (Marchetti, 2020)