Fellowship for Adam Bachstetter: Harnessing Microglia Toward Repair Vs. Damage: Does p38 MAPK Hold the Reins

It is becoming increasingly clear that, like peripheral immunity, an immune response in the central nervous system (CNS) is generally beneficial, but chronic or dysregulated neuroinflammation such as seen in Alzheimer's disease (AD) can be detrimental1 - 3 . The effector cells of the innate immune system in the CNS are activated glia (i.e., microglia and astrocytest A fine balance between the beneficial (e.g. clearance of aggregated and misfolded proteins, secretion of growth factors, and protection from pathogens) versus detrimental (e.g. oxidative damage, neuron loss, and edema) aspects of the CNS immune response is critically important5 - 9 • Dysregulated neuroinflammation can be described as a disruption of this balance. In the process of restoring homeostasis, the pendulum often swings too far the other way and the activated cells do not return to the resting state. Alternatively, the pendulum could swing the wrong way in the beginning if a pathogen (killing) response is activated instead of a homeostasis response. The goal of this proposal is to try and learn how to regain control of the pendulum and thereby tailor the immune response. .