The roles of glial cells in models of neurodegenerative disease. (360G-Wellcome-075045_Z_04_A)

My own work, using fluorescent imaging techniques during the rotation project, showed that Ab increases ROS generation by activation of the NADPH oxidase in BV2 cells and that inhibition of the CLIC1-mediated chloride conductance - with IAA-94, by transfecting cells with an siRNA against the CLIC1 protein or by substitution of Cl with non-permeant anions almost completely prevents that response. We propose that the activity of the NADPH oxidase is limited by charge compensation and that the chloride conductance plays a key role in augmenting the activity of the enzyme by providing a route for the compensation of electron flow across the membrane. CLIC1 is also expressed in astrocytes, but at present we have no data regarding its possible functions. The functions of this CLIC1-mediated chloride conductance, its mode of activation, the means by which its inhibition can reduce ROS production and neuronal death and its potential ubiquity and general importance in glial cell physiology will form the basis of the research to be undertaken during the course of this PhD.