Mechanisms of brain iron transport: insight into neurodegeneration and CNS disorders.
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.
Mills
Eric
E
The Department of Molecular, Cellular, and Developmental Biology, the University of Michigan, 3089 Natural Science Building (Kraus), 830 North University, Ann Arbor, MI 48109, USA.
Dong
Xian-Ping
XP
Wang
Fudi
F
Xu
Haoxing
H
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D002493:Central Nervous System Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D014131:Trace Elements / Q000378:metabolism
D014131:Trace Elements; D007501:Iron