Iron Neurotoxicity in Parkinson’s Disease

Abstract

Iron plays essential roles in the early development of cognitive processes and in the maintenance of neuronal functions in the mature brain; therefore, neurons have expeditious mechanisms to ensure a readily available iron supply. However, several neurodegenerative diseases present dysregulation of iron homeostasis derived from mitochondrial dysfunction, inflammatory conditions, decreased glutathione levels, and oxidative damage, resulting in downstream protein aggregation, lipid peroxidation, and nucleic acid modification. In this chapter, the mechanisms by which iron homeostasis is lost in Parkinson’s disease (PD) are discussed. The relevance of endogenous toxins such as mediators of mitochondrial dysfunction, the relationship between inflammation and iron dyshomeostasis, and the role of hepcidin as a neuroprotective agent are also addressed. A model is proposed that involves a positive feedback loop between mitochondrial dysfunction, inflammation, and increased iron content in dopaminergic neurons, which, if unchecked, ends in substantia nigra (SN) neuronal death.