Fig. 2
From: Hepcidin, an emerging and important player in brain iron homeostasis
Hepcidin regulation and action in brain cells. Hepcidin expression in the brain is often induced by inflammatory stimuli. Inflammatory cytokines increase iron import through DMT1, and decrease iron export due to FPN downregulation. This increases cellular iron-load, especially in neurons. During iron-load conditions, astrocytes and microglia have been shown to increase hepcidin production. This might be the case for neurons as well, but the data are still inconclusive. Use of ad-hepcidin protects neurons during iron-overload conditions, by controlling the activity of iron import and export proteins, like TFR1, DMT1, FPN. Also, ad-hepcidin reduces iron flux from BMVEC, which reduces brain iron-load. Recent data suggest an important role for Zip8 and Steap2 for NTBI entry into brain cells. BMVEC brain microvascular endothelial cell, CIL cellular iron-load, DMT1 divalent metal transporter 1, FPN ferroportin, Hepc hepcidin, IL-6 interleukin 6, NTBI non-transferrin bound iron, TFR1 transferrin receptor 1