title: Trypanosoma cruzi antioxidant enzymes as virulence factors in Chagas disease.
abstract: CONCLUSIONS
  Chagas disease (CD) affects several million people in Latin America and is spreading beyond its classical boundaries due to the migration of infected host and insect vectors, HIV co-infection, and blood transfusion. The current therapy is not adequate for treatment of the chronic phase of CD, and new drugs are warranted.
  
  
  BACKGROUND
  Trypanosoma cruzi is equipped with a specialized and complex network of antioxidant enzymes that are located at different subcellular compartments which defend the parasite against host oxidative assaults. Recently, strong evidence has emerged which indicates that enzyme components of the T. cruzi antioxidant network (cytosolic and mitochondrial peroxiredoxins and trypanothione synthetase) in naturally occurring strains act as a virulence factor for CD. This precept is recapitulated with the observed increased resistance of T. cruzi peroxirredoxins overexpressers to in vivo or in vitro nitroxidative stress conditions. In addition, the modulation of mitochondrial superoxide radical levels by iron superoxide dismutase (FeSODA) influences parasite programmed cell death, underscoring the role of this enzyme in parasite survival.
  
  
  RESULTS
  The unraveling of the biological significance of FeSODs in T. cruzi programmed cell death in the context of chronic infection in CD is still under examination.
  
  
  CONCLUSIONS
  The role of the antioxidant enzymes in the pathogenesis of CD, including parasite virulence and persistence, and their feasibility as pharmacological targets justifies further investigation.
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Lucía
authors.initials: L
authors.lastname: Piacenza
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Peluffo
authors.forename: María Noel
authors.initials: MN
authors.lastname: Alvarez
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martínez
authors.forename: Rafael
authors.initials: R
authors.lastname: Radi
mesh_terms: D000818:Animals; D017209:Apoptosis; D014355:Chagas Disease / Q000469:parasitology* / Q000473:pathology; D006790:Host-Parasite Interactions; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000502:physiology*; D015800:Protozoan Proteins / Q000502:physiology*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000472:pathogenicity / Q000502:physiology*; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D015800:Protozoan Proteins; D026361:Reactive Nitrogen Species; D037521:Virulence Factors; D009569:Nitric Oxide; D010088:Oxidoreductases