Abstract

The evidence for the participation of redox-active iron and reactive oxygen species (ROS) in a number of neurodegenerative diseases, including, Huntington’s disease, Alzheimer’s disease, Friedreich’s ataxia, Amyotrophic lateral sclerosis (ALS) and Parkinson’s disease is by now unquestionable. In particular, in the case of Parkinson's disease (PD) iron accumulation has been demonstrated in the dopaminergic neurons of the substantia nigra pars compacta and neuronal death in this area is prevented by pharmacological agents with iron chelating capacity. Other pathognomonic signs of PD include inhibition of mitochondrial complex I and decreased glutathione (GSH) content. In this chapter we will discuss the effects of complex I inhibition on Fe-S cluster synthesis and iron homeostasis, and the positive feedback loop between iron, glutathione and ROS that ends in cell death. We will also discuss the possible role of hepcidin as a mediator of inflammatory stimuli that trigger iron dishomeostasis.