title: Reactive Oxygen-Related Diseases: Therapeutic Targets and Emerging Clinical Indications.
abstract: CONCLUSIONS
  Enhanced levels of reactive oxygen species (ROS) have been associated with different disease states. Most attempts to validate and exploit these associations by chronic antioxidant therapies have provided disappointing results. Hence, the clinical relevance of ROS is still largely unclear.
  
  
  BACKGROUND
  We are now beginning to understand the reasons for these failures, which reside in the many important physiological roles of ROS in cell signaling. To exploit ROS therapeutically, it would be essential to define and treat the disease-relevant ROS at the right moment and leave physiological ROS formation intact. This breakthrough seems now within reach.
  
  
  RESULTS
  Rather than antioxidants, a new generation of protein targets for classical pharmacological agents includes ROS-forming or toxifying enzymes or proteins that are oxidatively damaged and can be functionally repaired.
  
  
  CONCLUSIONS
  Linking these target proteins in future to specific disease states and providing in each case proof of principle will be essential for translating the oxidative stress concept into the clinic.
authors.affiliation: 1 Department of Pharmacology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University , Maastricht, the Netherlands .
authors.forename: Ana I
authors.initials: AI
authors.lastname: Casas
authors.affiliation: 1 Department of Pharmacology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University , Maastricht, the Netherlands .
authors.forename: V Thao-Vi
authors.initials: VT
authors.lastname: Dao
authors.affiliation: 2 2nd Medical Department, Molecular Cardiology, University Medical Center , Mainz, Germany .
authors.forename: Andreas
authors.initials: A
authors.lastname: Daiber
authors.affiliation: 3 Victor Chang Cardiac Research Institute, and School of Medical Sciences, University of New South Wales , Sydney, New South Wales, Australia .
authors.forename: Ghassan J
authors.initials: GJ
authors.lastname: Maghzal
authors.affiliation: 4 Department of Biomedical Sciences, University of Padova , Italy .|5 Neuroscience Institute , CNR, Padova, Italy .
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
authors.affiliation: 5 Neuroscience Institute , CNR, Padova, Italy .
authors.forename: Nina
authors.initials: N
authors.lastname: Kaludercic
authors.affiliation: 6 Brighton and Sussex Medical School , Falmer, United Kingdom .
authors.forename: Sonia
authors.initials: S
authors.lastname: Leach
authors.affiliation: 7 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, Instituto de Investigaciones Biomédicas "Alberto Sols" UAM-CSIC, Instituto de Investigación Sanitaria La Paz (IdiPaz), Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid , Madrid, Spain .
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuadrado
authors.affiliation: 8 Department of Pathology and Immunology, Medical School, University of Geneva , Geneva, Switzerland .
authors.forename: Vincent
authors.initials: V
authors.lastname: Jaquet
authors.affiliation: 8 Department of Pathology and Immunology, Medical School, University of Geneva , Geneva, Switzerland .
authors.forename: Tamara
authors.initials: T
authors.lastname: Seredenina
authors.affiliation: 8 Department of Pathology and Immunology, Medical School, University of Geneva , Geneva, Switzerland .
authors.forename: Karl H
authors.initials: KH
authors.lastname: Krause
authors.affiliation: 9 Teofilo Hernando Institute, Department of Pharmacology, Faculty of Medicine. Autonomous University of Madrid , Madrid, Spain .
authors.forename: Manuela G
authors.initials: MG
authors.lastname: López
authors.affiliation: 3 Victor Chang Cardiac Research Institute, and School of Medical Sciences, University of New South Wales , Sydney, New South Wales, Australia .
authors.forename: Roland
authors.initials: R
authors.lastname: Stocker
authors.affiliation: 6 Brighton and Sussex Medical School , Falmer, United Kingdom .
authors.forename: Pietro
authors.initials: P
authors.lastname: Ghezzi
authors.affiliation: 1 Department of Pharmacology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University , Maastricht, the Netherlands .
authors.forename: Harald H H W
authors.initials: HH
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism; D019255:NADPH Oxidases / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D008995:Monoamine Oxidase; D019255:NADPH Oxidases