The Environmental Contribution to Redox Dyshomeostasis in Parkinson’s Disease

Abstract

One of the major scientific questions in Parkinson’s disease (PD) research is what makes the dopaminergic neurons in the substantia nigra pars compacta vulnerable. Since the early 90s, oxidative stress has been suggested to promote the loss of dopaminergic cells. Oxidative stress is defined as an increase in the steady-state levels of reactive oxygen species. Cells have evolved antioxidant systems and a wide range of mechanisms for the removal or repair of oxidative damage, but disease follows when these processes are surpassed by oxidative damage. The three major risk factors linked to PD (aging, environmental exposures and genetic alterations) have been reported to promote oxidative damage. As such, post-mortem analysis of PD brains has demonstrated an increased accumulation of oxidized proteins, nucleic acids and lipids. In this chapter, we provide an overview to redox homeostasis and the pathogenic mechanisms involved in the alterations in redox homeostasis that occurs in PD. We will discuss the intrinsic properties of dopaminergic neurons that make them vulnerable to oxidative damage, and the mechanisms by which alterations in the cellular redox homeostasis contribute to neurodegeneration. We will also overview how environmental toxicants disrupt redox homeostasis in neuronal cells and glial populations.KeywordsParkinson’s diseaseRedox homeostasisOxidative stressReactive oxygen speciesAntioxidantsα-synuclein