Targeting NOX enzymes in the central nervous system: therapeutic opportunities

• Published in: Cellular and molecular life sciences : CMLS Vol. 69; no. 14; pp. 2387 - 2407
• Main Authors: Sorce, Silvia, Krause, Karl-Heinz, Jaquet, Vincent
• Format: Journal Article
• Language: English
• Published: Basel Springer-Verlag 01.07.2012; SP Birkhäuser Verlag Basel; Springer Nature B.V
• Subjects: Alzheimer disease; Alzheimer's disease; Amyotrophic lateral sclerosis; Antioxidants; Autoimmune diseases; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Central nervous system; Central Nervous System Diseases - enzymology; Central Nervous System Diseases - pathology; Central Nervous System Diseases - therapy; Clinical trials; Demyelinating diseases; Demyelination; diseases; Disorders; drugs; Enzyme Inhibitors - therapeutic use; Enzymes; Humans; Immune response; Immunosuppressive agents; Life Sciences; Mental disorders; Movement disorders; Multi-Author Review; NAD(P)H oxidase; NAD(P)H oxidase (H2O2-forming); NADP (coenzyme); NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - metabolism; Neurodegenerative diseases; Neurological disorders; Oxidative stress; Oxygen; Parkinson disease; Parkinson's disease; Pathology; Protein Isoforms - antagonists & inhibitors; Protein Isoforms - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Schizophrenia; Small Molecule Libraries - chemical synthesis; Small Molecule Libraries - chemistry; Small Molecule Libraries - therapeutic use; stroke; therapeutics; Antioxidants; NOX inhibitors; Oxidative stress; Brain; Stroke; NOX NADPH oxidase; Central nervous system; Schizophrenia; Autoimmune diseases; Alzheimer; Parkinson
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-012-1014-5

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.