Iron in the brain: An important contributor in normal and diseased states

Iron is essential for normal neurological function because of its role in oxidative metabolism and because it is a cofactor in the synthesis of neurotransmitters and myelin. In the past several years, there has been increased attention to the importance of oxidative stress in the central nervous system. Iron is the most important inducer of reactive oxygen species, therefore, the relation of iron to neurodegenerative processes is more appreciated today than it was a few years ago. Nevertheless, despite this increased attention and awareness, our knowledge of iron metabolism in the brain at the cellular and molecular levels is still limited. Iron is distributed in a heterogeneous fashion among the different regions and cells of the brain. This regional and cellular heterogeneity is preserved across many species. Brain iron concentrations are not static; they increase with age and in many diseases and decrease when iron is deficient in the diet. In infants and children, insufficient iron in the diet is associated with decreased brain iron and with changes in behavior and cognitive functioning. Abnormal iron accumulation in the diseased brain areas and, in some cases, alterations in iron-related proteins have been reported in many neurodegenerative diseases, including, Hallervorden-Spatz syndrome, Alzheimer's disease, Parkinson's disease, and Friedreich's ataxia. There is strong evidence for iron-mediated oxidative damage as a primary contributor to cell death in these disorders. Demyelinating diseases, such as multiple sclerosis, especially warrant study in relation to iron availability. Myelin synthesis and maintenance have a high iron requirement, thus, oligodendrocytes must have a relatively high and constant supply of iron. However, the high oxygen utilization, high density of lipids, and high iron content of white matter all combine to increase the risk of oxidative damage. We review here the current knowledge of the normal metabolism of iron in the brain and the suspected role of iron in neuropathology.