"Use of human pluripotent stem cells to study the role of Nox2 in neural differentiation"

Abstract

High amount of ROS production is involved in various neurodegenerative diseases. It has been well documented that NOX mediated ROS plays an important role as a second messenger in activating multiple signaling pathway such as inflammation, DNA damage and cell death. However, interestingly a certain amount of ROS mediated by NOX2 has enzyme has been shown recently to be involved in proliferative neural stem cells in the dentate gyrus (DG) and sub ventricular zone(SVZ) known as adult neurogenic niche in the brain. These regions are responsible to generate new neurons and have an important role in memory formation. Accordingly, it has been demonstrated that NOX2 deficiencies in mice with chronic granulomatous disease (CGD) have synaptic plasticity deficit and mild memory impairment. Similarly, there is a cognitive dysfunction in patients with CGD.

The immunological aspects of NOX2 deficiency in CGD has been widely studied in. In the contrary, there is not much known about NOX2 in functional aspect in the brain of these patients. For this induced pluripotent stem cells (iPS) has been generated from patients with CGD as a tool to study the role of NOX2 generating ROS, the cells were differentiated toward neural cell lineage and NOX2 expression at the transcriptional and protein level has been analyzed.