title: New insights on NOX enzymes in the central nervous system.
abstract: CONCLUSIONS
  There is increasing evidence that the generation of reactive oxygen species (ROS) in the central nervous system (CNS) involves the NOX family of nicotinamide adenine dinucleotide phosphate oxidases. Controlled ROS generation appears necessary for optimal functioning of the CNS through fine-tuning of redox-sensitive signaling pathways, while overshooting ROS generation will lead to oxidative stress and CNS disease.
  
  
  BACKGROUND
  NOX enzymes are not only restricted to microglia (i.e. brain phagocytes) but also expressed in neurons, astrocytes, and the neurovascular system. NOX enzymes are involved in CNS development, neural stem cell biology, and the function of mature neurons. While NOX2 appears to be a major source of pathological oxidative stress in the CNS, other NOX isoforms might also be of importance, for example, NOX4 in stroke. Globally speaking, there is now convincing evidence for a role of NOX enzymes in various neurodegenerative diseases, cerebrovascular diseases, and psychosis-related disorders.
  
  
  RESULTS
  The relative importance of specific ROS sources (e.g., NOX enzymes vs. mitochondria; NOX2 vs. NOX4) in different pathological processes needs further investigation. The absence of specific inhibitors limits the possibility to investigate specific therapeutic strategies. The uncritical use of non-specific inhibitors (e.g., apocynin, diphenylene iodonium) and poorly validated antibodies may lead to misleading conclusions.
  
  
  CONCLUSIONS
  Physiological and pathophysiological studies with cell-type-specific knock-out mice will be necessary to delineate the precise functions of NOX enzymes and their implications in pathomechanisms. The development of CNS-permeant, specific NOX inhibitors will be necessary to advance toward therapeutic applications.
authors.affiliation: 1 Department of Pathology and Immunology, Geneva Medical Faculty, Geneva University Hospitals, Centre Médical Universitaire , Geneva, Switzerland .
authors.forename: Zeynab
authors.initials: Z
authors.lastname: Nayernia
authors.forename: Vincent
authors.initials: V
authors.lastname: Jaquet
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Krause
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000201:enzymology / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000201:enzymology* / Q000473:pathology / Q000628:therapy*; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases