FIGURE 3.

Schematic illustration showing several effects of microglia on iron metabolism and degeneration of DA neurons in PD. (1) Iron overload-induced activation of microglia increases the release of Lf, which provides neuroprotection against MPP⁺ in DA neurons. (2) LPS could induce the release of IL-6 in microglia, which could increase the expression of hepcidin in DA neurons, thus inhibiting FPN1-mediated iron efflux in DA neurons. (3) Excessive activation of microglia induced by LPS or neurotoxins could release IL-1β and TNF-α, which aggravates iron accumulation of DA neurons by up-regulating DMT1+IRE and down-regulating FPN1. (4) MMP-9 released by damaged DA neurons could lead to upregulation and release of LCN2. LCN2 then activates microglia to release TNF-α and IL-1β, which is involved in the abnormal expression of DMT1 and FPN1 in DA neurons. LCN2 released from activated microglia might also induce direct neurotoxicity via excessive iron delivery into DA neurons by binding to LCN2 receptors.