Oxidative stress and inflammation in Parkinson's disease: is there a causal link?

Exp Neurol. 2005 Jun;193(2):279-90. doi: 10.1016/j.expneurol.2005.01.013.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a dramatic loss of dopaminergic neurons in the substantia nigra (SN). Among the many pathogenic mechanisms thought to contribute to the demise of these cells, dopamine-dependent oxidative stress has classically taken center stage due to extensive experimental evidence showing that dopamine-derived reactive oxygen species and oxidized dopamine metabolites are toxic to nigral neurons. In recent years, however, the involvement of neuro-inflammatory processes in nigral degeneration has gained increasing attention. Not only have activated microglia and increased levels of inflammatory mediators been detected in the striatum of deceased PD patients, but a large body of animal studies points to a contributory role of inflammation in dopaminergic cell loss. Recently, postmortem examination of human subjects exposed to the parkinsonism-inducing toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), revealed the presence of activated microglia decades after drug exposure, suggesting that even a brief pathogenic insult can induce an ongoing inflammatory response. Perhaps not surprisingly, non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of developing PD. In the past few years, various pathways have come to light that could link dopamine-dependent oxidative stress and microglial activation, finally ascribing a pathogenic trigger to the chronic inflammatory response characteristic of PD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Disease Models, Animal
  • Dopamine / metabolism
  • Encephalitis / drug therapy
  • Encephalitis / etiology*
  • Encephalitis / pathology
  • Humans
  • Microglia / physiology
  • Mitochondria / physiology
  • Models, Neurological
  • Oxidative Stress / physiology*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology*

Substances

  • Anti-Inflammatory Agents
  • Dopamine