Unraveling the Burden of Iron in Neurodegeneration: Intersections with Amyloid Beta Peptide Pathology

Figure 1

Iron and Aβ interactions. Transferrin-bound iron is taken up by the neuron via a receptor- (TfR) mediated mechanism. An augmented pool of intracellular iron (mainly as Fe²⁺) increases ROS production with the concomitant generation of oxidative stress. Mitochondrial ferritin is able to protect the neuron against iron-induced oxidative stress. Iron itself is able to induce APP expression through an APP IRE. Also, APP mediates iron export via FPN. An increased APP expression (due to an increased iron uptake) results in an increased Aβ generation. Interestingly, iron is involved in Aβ aggregation in a mechanism that generates oxidative stress, but it is also known that previous oxidative stress increases Aβ aggregation. In this way, both Aβ and iron participate in a vicious cycle known to culminate with synaptic oxidative injury.