title: Oxidative stress and microglial cells in Parkinson's disease.
abstract: Significant evidence has now been accumulated that microglial cells play a central role in the degeneration of DA neurons in animal models of PD. The oxidative stress response by microglial cells, most notably the activity of the enzyme NADPH oxidase, appears to play a central role in the pathology of PD. This oxidative stress response occurs in microglia through the activation of the ERK signaling pathway by proinflammatory stimuli, leading to the phosphorylation and translocation of the p47(phox) and p67(phox) cytosolic subunits, the activation of membrane-bound PHOX, and the production of ROS. Therapeutic anti-inflammatories which prevent DA neurodegeneration in PD, including anti-inflammatory cytokines, morphinan compounds, NADPH oxidase inhibitors, NF-κB inhibitors, and β2-AR agonists, all function to inhibit the activation of the PHOX in microglial cells. These observations suggest a central role for the oxidative stress response in microglial cells as a mediator or regulator of DA neurodegeneration in PD.
authors.affiliation: North Carolina Oral Health Institute, The University of North Carolina at Chapel Hill, CB#7454, Chapel Hill, NC 27599-7454, USA.
authors.forename: Lynda J
authors.initials: LJ
authors.lastname: Peterson
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Flood
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism*; D010766:Phosphorylation; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D048049:Extracellular Signal-Regulated MAP Kinases