INVOLVEMENT OF OXIDATIVE STRESS IN THE PATHOGENESIS OF SCHIZOPHRENIA:FOCUS ON NOX ENZYMES

The imbalance between the production of reactive oxygen species (ROS) and the cellular antioxidant defence, determines a situation called “oxidative stress”. ROS react and oxidize cellular components, such as proteins or DNA, leading to cell death and severe tissue damage. The central nervous system (CNS) is particularly sensitive to oxidative stress because of high oxygen consumption, low antioxidant defense and abundance of lipids, which are prone to oxidation. For this reason a variety of CNS diseases have an oxidative stress component. In the CNS, NOX NADPH oxidases are increasingly recognized as major sources of ROS. Among the seven existing isoforms, the presence of NOX1, NOX2, NOX3 and NOX4 transcripts has been detected in total brain samples. In addition, several immunohistological and in vitro studies have investigated the expression of NOX isoforms in specific CNS regions and cells. From these studies, it appears that NOX1, NOX2 and NOX4 are present in microglia, neurons and astrocytes. Although the physiological role of constitutive NOX expression in the brain is still poorly understood, several researches suggest that they are involved in brain development and function, but most studies indicate that an excessive production of ROS by NOX enzymes participates to the progression of various neurological and psychiatric diseases. The aim of this research project was to investigate the role of NOX2 in the pathogenesis of schizophrenia.