Brain Iron Metabolism
Section snippets
How Does Iron Cross the Blood-Brain Barrier and Move Within the CNS?
For many years, it was believed that iron entered the brain mainly during infancy before the blood-brain barrier matured. However, in the last decade, it has become apparent that brain-iron uptake is mediated by endothelial TfR expression in the blood-brain barrier of adult animals, and this TfR expression on the luminal endothelial surface is regulated by the iron status of the CNS. The blood-brain barrier is an unusual structure composed of endothelial cells, a basal lamina, pericytes, and
Iron Redistribution With the Brain
After initial uptake in the brain, iron redistributes into various areas of the brain,68, 69 but the mechanisms by which iron redistributes in the brain are poorly understood. Studies in hypotransferrinemic mice suggest that redistribution of iron depends on the presence of intact Tf in brain interstitial fluid.70 As previously stated, Tf synthesized by oligodendrocytes does not return to the systemic circulation,71 presumably because CNS Tf cannot cross the tight epithelial cells of the
Misregulation of Brain Iron Metabolism and Neurodegeneration
In addition to the observation that iron accumulates abnormally in the brain of patients with sporadic Parkinson and Alzheimer diseases, abnormal accumulations of iron are also found in diseases with known genetic causes, including aceruloplasminemia,75 neurodegeneration with brain iron accumulation,76 and neuroferritinopathy.77 The usual hypothesis associated with these diseases is that abnormal accumulations of iron lead to increased formation of reactive oxygen species because ferrous iron
Future Directions
The axis that governs brain iron homeostasis has been partially described because it seems clear that endothelial TfR determines how much iron the brain will absorb. However, it is unclear how the brain and spinal cord gauge iron status and communicate this information to the blood brain barrier. To identify candidates for this role, the cells that express TfR2 should be identified because cells that express TfR2 could be functionally similar to hepatocytes. In addition, identifying the site of
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Supported by the intramural program of the National Institute of Child Health and Human Development.