Abstract
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 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 as being 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.
Financial & competing interests disclosure
The work in the Xu laboratory is supported by startup funds to H Xu from the Department of MCDB and Biological Science Scholar Program, the University of Michigan, USA, an NIH RO1 grant (NS062792 to H Xu), pilot grants (to H Xu) from the UM Initiative on Rare Disease Research, Michigan Alzheimer’s Disease Research Center (NIH grant P50-AG08671 to Gilman), and National Multiple Sclerosis Society. F Wang is supported by Chinese Academy of Sciences One Hundred Talents Program (KSCX2-YW-R-151) and National Basic Research Program of China (973 Program; 2009CB941400).
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript. We appreciate the encouragement and helpful comments from other members of the Xu laboratory.