ABSTRACT
Oxidative stress associated with cell death in progressive neurological disease often involves the loss of metal homeostasis, resulting in increased generation of free radicals and loss of mitochondrial function. Radical formation can lead to lipid peroxidation and ultimately loss of plasma membrane integrity. Iron is a transition metal that plays an important functional role in many biological processes. However, even in a bound form, iron is dangerous owing to its ability to increase oxidative stress through conversion of H2O2 to more reactive ROS such as the hydroxyl radical (Fenton reaction). There is evidence that iron can be mobilized and redistributed from cell storage pools after brain insult. Some of this redistribution is not only intracellular but also intercellular, involving glial cells. The redistribution of iron may result in increased cellular vulnerability of some glial cells and dysfunction of others that ultimately promotes neurodegeneration and therefore may exacerbate the disease process. There are also important cellular functions and interactions that are iron dependent. Therefore, iron homeostasis is key to normal neurological function. The role of glial cells in maintaining brain iron homeostasis and the consequence of loss of homeostasis is discussed in this chapter.
