ObjectivesThis study aims to elucidate the links between neuroinflammation, NADPH-oxidases (NOX) enzymes and neurological disorders (ND), prospectively assessing NOX2 activity in a cohort of patients affected by Amyotrophic Lateral Sclerosis (ALS), Parkinson’s Disease (PD) and respective healthy controls.BackgroundNOX catalyse the formation of Reactive Oxygen Species (ROS), which play a role in the development of ND, particularly whose generated by the phagocytic isoform NOX2. Increased ROS has been observed in the pre-clinical model of ALS (SOD1 transgenic mouse) and in ALS patients. There is also evidence that NOX are expressed and activated in patients with PD and other ND as compared to healthy controls.Design/MethodsNeutrophil and monocyte oxidative burst was measured directly in fresh blood using Phagoburst™ assay by flow cytometry. Mean fluorescence intensity (MFI), emitted in response to different stimuli, leads to produce ROS and corresponds to the percentage of oxidizing cells and their enzymatic activity (GeoMean). Sixty ALS patients, meeting El Escorial revised diagnostic criteria, and forty PD patients have been enrolled in the study. Healthy age- and gender-matched control subjects, chosen among patients caregivers, were also recruited following informed consent.ResultsPreliminary results put in evidence statistically significant differences between ALS patients and controls. Moreover, comparing the individual measured oxidative MFI with reference parameters, we verified higher out-range values in granulocytes and monocytes GeoMean in 63% and 23% of ALS patients, while this trend was reduced in the controls to 25% and 12%. Similar findings were found in PD patients (37.5% and 20%) and in controls percentage was 15 and 7 for granulocytes and monocytes.ConclusionsData currently obtained seem to suggest an involvement of NOX in the formation of ROS in patients with the analyzed ND. Next follow-up will be needed to confirm this hypothesis and better assess their role in ND.Study supported by European Community's Framework Programme (FP7/2007-2013) under grant agreement n° 278611
Role of NOX2 enzyme activity in neuroinflammation: preliminary results in Amyotrophic Lateral Sclerosis and Parkinson’s disease
CALVO, Andrea;SALAMONE, PAOLINA;MARRALI, GIUSEPPE;CASALE, Federico;FUDA, Giuseppe;AMOROSO, Antonio;Zibetti M;RIZZONE, Mario Giorgio;LOPIANO, Leonardo;CHIO', Adriano
2014-01-01
Abstract
ObjectivesThis study aims to elucidate the links between neuroinflammation, NADPH-oxidases (NOX) enzymes and neurological disorders (ND), prospectively assessing NOX2 activity in a cohort of patients affected by Amyotrophic Lateral Sclerosis (ALS), Parkinson’s Disease (PD) and respective healthy controls.BackgroundNOX catalyse the formation of Reactive Oxygen Species (ROS), which play a role in the development of ND, particularly whose generated by the phagocytic isoform NOX2. Increased ROS has been observed in the pre-clinical model of ALS (SOD1 transgenic mouse) and in ALS patients. There is also evidence that NOX are expressed and activated in patients with PD and other ND as compared to healthy controls.Design/MethodsNeutrophil and monocyte oxidative burst was measured directly in fresh blood using Phagoburst™ assay by flow cytometry. Mean fluorescence intensity (MFI), emitted in response to different stimuli, leads to produce ROS and corresponds to the percentage of oxidizing cells and their enzymatic activity (GeoMean). Sixty ALS patients, meeting El Escorial revised diagnostic criteria, and forty PD patients have been enrolled in the study. Healthy age- and gender-matched control subjects, chosen among patients caregivers, were also recruited following informed consent.ResultsPreliminary results put in evidence statistically significant differences between ALS patients and controls. Moreover, comparing the individual measured oxidative MFI with reference parameters, we verified higher out-range values in granulocytes and monocytes GeoMean in 63% and 23% of ALS patients, while this trend was reduced in the controls to 25% and 12%. Similar findings were found in PD patients (37.5% and 20%) and in controls percentage was 15 and 7 for granulocytes and monocytes.ConclusionsData currently obtained seem to suggest an involvement of NOX in the formation of ROS in patients with the analyzed ND. Next follow-up will be needed to confirm this hypothesis and better assess their role in ND.Study supported by European Community's Framework Programme (FP7/2007-2013) under grant agreement n° 278611
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