Chapter 10 - Oxidative stress signaling and regulated cell death in Parkinson's disease

Abstract

In 2017, the world celebrated the 200th anniversary of James Parkinson's first description of six individuals with atypical body movements and postural abnormalities in An Essay on the Shaking Palsy (1817). These features, together with nonmotor symptoms, are known today as Parkinson's disease (PD). Despite several advances in the understanding of the pathophysiology of the disorder, there is to date no proven neuroprotective or neurorestorative therapy for PD. Several advances in the understanding of environmental and genetic factors as causes of PD have created an opportunity to develop mechanistic-based therapies. However, how genetic–environmental factors interact remains a matter of intense investigation. The authors present a model of minimal completeness of cell death signaling induced by genetic and environmental oxidative stress as a mechanistic explanation of the dopaminergic neuronal demise observed in PD. This mechanism holds particular promise for identifying agents that slow and even halt the progression of PD.