Targeting NOX enzymes in the central nervous system: therapeutic opportunities.
Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologies.
Department of Pathology and Immunology, Geneva Medical Faculty, Geneva University Hospitals Centre Medical Universitaire, Switzerland.
Silvia
S
Sorce
Karl-Heinz
KH
Krause
Vincent
V
Jaquet
D002493:Central Nervous System Diseases / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D054852:Small Molecule Libraries; D019255:NADPH Oxidases