Cellular and regional maintenance of iron homeostasis in the brain: normal and diseased states
Iron is an essential trophic factor for normal development of the brain and for maintenance of normal neurological function throughout life. However, iron when not regulated, can become a potent toxin through its ability to induce lipid peroxidative damage. Consequently, the brain has an exquisite system to assure the availability and timely delivery of iron. In this manuscript we review the cellular and regional distribution of the proteins involved in mediating the regulation of iron in the brain. These proteins, transferrin and its receptor (iron mobilization) and ferritin (iron storage) are thus responsible (along with the cells in which they reside) for maintaining iron homeostasis in the brain. Within the brain, iron and iron regulatory proteins have a region specific distribution being especially abundant in areas associated with motor functions. At the cellular level oligodendrocytes are the predominant cell type to stain for iron, transferrin and ferritin; although, numerous ferritin-positive microglial cells are present. Preliminary data from an analysis of isoforms of ferritin in the brain which may provide insight into the role of each cell type in iron regulation are discussed herein.
We further review the cellular and regional alterations which occur in the brain in such diseases as Alzheimer’s, Parkinson’s and Multiple Sclerosis in which a disruption in iron homeostasis may be part of the pathogenesis of these diseases.
KeywordsTransferrin Receptor Superior Temporal Gyrus Iron Homeostasis Brain Iron Central Pontine Myelinolysis
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