Role of a Stress Kinase in AD Pathogenesis

Narayan Bhat, PhD Medical University of South Carolina


The project investigates the role of a key cell signaling pathway commonly involved in cell stress and inflammatory responses i.e., p38 MAP kinase in multiple pathogenic processes of Alzheimer's disease (AD) including neuroinflammation, tau phosphorylation, amyloid deposition and synaptic dysfunction. The approach uses a genetic conditional knockout strategy to cell-specifically delete the kinase in microglia and forebrain neurons in a mouse model of AD. The outcome will provide mechanistic insight into AD-associated pathogenic processes and define the signaling pathway as a versatile treatment target for AD.

Project Details

The protein called “p38 MAP kinase” is important for many functions in the body, and problems with this protein can cause inflammation and interrupt nerve cell communication in Alzheimer's disease. Dr. Narayan Bhat and collaborators plan to create and study a new mouse model of Alzheimer's. To make this model, they will change the p38 MAP kinase proteins in two parts of the brain, namely in immune cells called microglia, and at the points where the nerve cells communicate, called synapses. The changes in microglia, synapses and overall brain health will be monitored by state‐of‐the‐art techniques, including labeling cells with a special dye and examining them under a special microscope. Information obtained from this study may help to direct future drug therapies.