Fig. 3.

Iron homeostasis in neurones. Neurones and glial cells can uptake iron bound to transferrin (TBI), or bound to other molecules such as citrate and ATP secreted by astrocytes (NTBI). Neuronal uptake of TBI is enabled by the transferrin receptor located at the cell membrane and the uptake of NTBI in inflammatory conditions is probably enabled by DMT1. DMT1 and TfR1 complexes are internalised via endocytosis, ultimately resulting in the release of redox-active iron (Fe(II)) into the cytosol and the return of other molecules in the complexes to the plasma membrane. Once in the cytosol, Fe(II) can be utilised for various essential metabolic processes such as the synthesis of iron-sulphur proteins, or sequestrated by cytosolic ferritin and mitochondrial ferritin (FtMt), which offers protection against the advent of the Fenton reaction. Iron is removed from neurones by ferroportin, supported by the multi-copper-containing ferroxidase caeruloplasmin and sAPP, which both act to stabilise ferroportin at the cell surface