Trace metals such as iron, copper, zinc, manganese, and cobalt are essential cofactors for many cellular enzymes. Extensive research on iron, the most abundant transition metal in biology, has contributed to an increased understanding of the molecular machinery involved in maintaining its homeostasis in mammalian peripheral tissues. However, the cellular and intercellular iron transport mechanisms in the central nervous system (CNS) are still poorly understood. Accumulating evidence suggests that impaired iron metabolism is an initial cause of neurodegeneration, and several common genetic and sporadic neurodegenerative disorders have been proposed to be associated with dysregulated CNS iron homeostasis. This review aims to provide a summary of the molecular mechanisms of brain iron transport. Our discussion is focused on iron transport across endothelial cells of the blood-brain barrier and within the neuro- and glial-vascular units of the brain, with the aim of revealing novel therapeutic targets for neurodegenerative and CNS disorders.
Keywords: Blood-brain barrier (BBB); Reactive-Oxygen Species (ROS); brain vascular endothelial cell (BVEC); divalent metal transporter-1 (DMT1, Slc11a2); early endosome (EE); ferritin (Ft); ferroportin (Fpn); non-transferrin-bound iron (NTBI); transferrin (Tf); transient receptor potential mucolipin 1 (TRPML1).