Abstract

Iron plays essential roles in the development of early cognitive functions and in the maintenance of neuronal functions in the mature brain, so neurons have in place expeditious mechanisms to ensure a readily available supply of iron. However, iron is an intrinsic producer of reactive oxygen species (ROS), and increased levels of iron promote neurotoxicity because of hydroxyl radical formation, glutathione consumption, protein aggregation, lipid peroxidation, and nucleic acid modification. In this chapter, the components of iron homeostasis and the mechanisms by which iron homeostasis is lost in Parkinson’s disease (PD) are discussed. In particular, it will be discussed the relevance of endogenous toxins such as aminochrome as mediators of mitochondrial dysfunction and of hepcidin as a mediator of inflammatory stimuli. A model is proposed that describes a positive feedback loop between changes in iron, glutathione, and ROS levels that ends in cell death.