The role of oxidative stress in Parkinson's disease

J Parkinsons Dis. 2013;3(4):461-91. doi: 10.3233/JPD-130230.


Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Disruptions in the physiologic maintenance of the redox potential in neurons interfere with several biological processes, ultimately leading to cell death. Evidence has been developed for oxidative and nitrative damage to key cellular components in the PD substantia nigra. A number of sources and mechanisms for the generation of reactive oxygen species (ROS) are recognized including the metabolism of dopamine itself, mitochondrial dysfunction, iron, neuroinflammatory cells, calcium, and aging. PD causing gene products including DJ-1, PINK1, parkin, alpha-synuclein and LRRK2 also impact in complex ways mitochondrial function leading to exacerbation of ROS generation and susceptibility to oxidative stress. Additionally, cellular homeostatic processes including the ubiquitin-proteasome system and mitophagy are impacted by oxidative stress. It is apparent that the interplay between these various mechanisms contributes to neurodegeneration in PD as a feed forward scenario where primary insults lead to oxidative stress, which damages key cellular pathogenetic proteins that in turn cause more ROS production. Animal models of PD have yielded some insights into the molecular pathways of neuronal degeneration and highlighted previously unknown mechanisms by which oxidative stress contributes to PD. However, therapeutic attempts to target the general state of oxidative stress in clinical trials have failed to demonstrate an impact on disease progression. Recent knowledge gained about the specific mechanisms related to PD gene products that modulate ROS production and the response of neurons to stress may provide targeted new approaches towards neuroprotection.

Keywords: Neurodegeneration; dopamine; mitochondria; neuroinflammation; neuroprotection; reactive oxygen species.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism
  • Dopamine / metabolism
  • Dopaminergic Neurons / metabolism*
  • Glutathione / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Iron / metabolism
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Lipid Metabolism
  • Melanins / metabolism
  • Mitochondria / metabolism
  • Oncogene Proteins / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • Parkinson Disease / metabolism*
  • Protein Deglycase DJ-1
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • alpha-Synuclein / metabolism


  • Intracellular Signaling Peptides and Proteins
  • Melanins
  • Oncogene Proteins
  • Ubiquitin
  • alpha-Synuclein
  • neuromelanin
  • Iron
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • PTEN-induced putative kinase
  • Protein Serine-Threonine Kinases
  • PARK7 protein, human
  • Protein Deglycase DJ-1
  • Glutathione
  • Calcium
  • Dopamine