Brandy Wilkenson, Ph.D.
blw9@case.edu
The goal of my current project is to elucidate mechanisms mediating the microglia pro-inflammatory response to fibrillar beta amyloid (fAß). The interaction of microglia with Aß plaques leads to the induction of proinflammatory signaling cascades and the release of neurotoxic secretory products. Previous studies have shown fAß-stimulated ROS production from the activation of the microglial NADPH oxidase. The NADPH oxidase consists of the membrane associated flavoprotein cytochrome b558 and the cytosolic, p47phox, p67phox, p40phox, and Rac1. Little is known about the Aß-stimulated intracellular signaling pathways responsible for this activation. We hypothesize that fAß engagement of a newly discovered multireceptor cell surface complex on microglia leads to the production of ROS and subsequent neuronal damage. My work focuses on uncovering the signaling cascades responsible for the assembly and activation of the NADPH oxidase following fAß stimulation. Specifically, I am examining the signaling events responsible for Rac GTP loading and phosphorylation of the p47phox and p67phox subunits. |
