Role of ROS in AB42 mediated cell surface P-selectin expression and actin polymerization

Abstract

Blood-brain barrier dysfunction plays an important role in the onset and progression of Alzheimer's disease (AD). In the AD brains an increased deposition of A(3 in the cerebral vasculature has been found to correlate with increased transmigration of blood-born inflammatory cells and neurovascular inflammation [1]. Transmigration of leukocytes into brain parenchyma is a sequential process starting with primary capture to the endothelium and rolling adhesion mediated by tethering on selectins and selectin ligands. P-selectin is a type I transmembrane cell adhesion molecule which is stored in cytoplasmic Weibel-Palade bodies (WPb) and can be mobilized on the endothelial cell surface within minutes upon exposure to different pro-inflammatory agents; then it's rapidly cleared through endocytosis in 30 min. It has become evident that A(3 activates cerebral endothelial cells (CECs) and induces mobilization of P-selectin to the cell surface [2]. However, expression mechanisms of this receptor on the surface of brain endothelial cells under administration with A(342 remain unclear. Since P-selectin is stored in WPb, and there is an evidence of active role of ROS (reactive oxygen species) and actin filaments in the different stages of WPb exocytosis, in this study we examined the dynamic of P-selectin expression on the endothelial cell surface activated by A(342 in relation to ROS and actin polymerization.