Chapter 2 - Pathological evidence for oxidative stress in Parkinson's disease and related degenerative disorders

Abstract

The notion of free radical involvement in Parkinson's disease (PD) arose from the recognition that both the autooxidation and enzymatic metabolism of dopamine produce potentially toxic free radicals and reactive oxidant species. Iron accumulation is not selectively associated with nigral cell damage or with PD. It would seem, therefore, that alterations in iron metabolism in PD must presently be viewed as a probable secondary phenomenon common to many degenerative illnesses and that a primary change in iron-mediated systems cannot be directly implicated in the aetiopathogenesis of PD. Changes in superoxide dismutase (SOD) activity in PD have been measured in two studies. An increase in the inducible Mn-dependent mitochondrial form of SOD in the substantia nigra (SNc) is observed but not in the cerebellum of PD patients. The finding of oxidative damage would support the notion that oxidant stress was a contributing factor to cell death in PD. There is some evidence to suggest that oxidative damage does occur in the SNc in PD. The role of levodopa in alterations in indices of oxidative stress is also elaborated.