title: NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress.
abstract: CONCLUSIONS
  NOX2 is important for host defense, and yet is implicated in a large number of diseases in which inflammation plays a role in pathogenesis. These include acute and chronic lung inflammatory diseases, stroke, traumatic brain injury, and neurodegenerative diseases, including Alzheimer's and Parkinson's Diseases.
  
  
  BACKGROUND
  Recent drug development programs have targeted several NOX isoforms that are implicated in a variety of diseases. The focus has been primarily on NOX4 and NOX1 rather than on NOX2, due, in part, to concerns about possible immunosuppressive side effects. Nevertheless, NOX2 clearly contributes to the pathogenesis of many inflammatory diseases, and its inhibition is predicted to provide a novel therapeutic approach.
  
  
  RESULTS
  Possible side effects that might arise from targeting NOX2 are discussed, including the possibility that such inhibition will contribute to increased infections and/or autoimmune disorders. The state of the field with regard to existing NOX2 inhibitors and targeted development of novel inhibitors is also summarized.
  
  
  CONCLUSIONS
  NOX2 inhibitors show particular promise for the treatment of inflammatory diseases, both acute and chronic. Theoretical side effects include pro-inflammatory and autoimmune complications and should be considered in any therapeutic program, but in our opinion, available data do not indicate that they are sufficiently likely to eliminate NOX2 as a drug target, particularly when weighed against the seriousness of many NOX2-related indications. Model studies demonstrating efficacy with minimal side effects are needed to encourage future development of NOX2 inhibitors as therapeutic agents.
authors: 1 Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, Georgia.
authors: Becky A
authors: BA
authors: Diebold
authors: 2 Department of Biology and Physics, Kennesaw State University , Kennesaw, Georgia.
authors: Susan M E
authors: SM
authors: Smith
authors: 1 Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, Georgia.
authors: Yang
authors: Y
authors: Li
authors: 1 Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, Georgia.
authors: J David
authors: JD
authors: Lambeth
mesh_terms: D000818:Animals; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases