Microglia are important in clearing amyloid-beta (Aβ) plaques, which are a primary feature of AD. Our previous research demonstrated that GPR3, a G protein-coupled receptor, can reduce soluble Aβ levels and lead to increased compaction of Aβ plaques and reduced plaque area in a preclinical AD mouse model. These findings suggest that microglia's response to GPR3 signaling may help limit the formation of Aβ plaques in AD mice. However, we still don't fully understand how GPR3 signaling restricts the growth of Aβ plaques in microglia.

During my postdoc under Professor Aizenman's guidance, we explored innovative approaches to reprogram microglia activation. Our research uncovered a correlation between the inhibition of the Hv1 proton channel and changes in the energy metabolism of microglia during activation, which facilitated neuroprotection in the event of excitotoxic damage. Building upon the tools we developed in this model, we investigated the mechanisms by which microglia activation impedes glial scar formation. We determined that microglia activation, specifically pro-inflammatory, impedes the glial scar formation by reducing its ability to increase.

In a collaborative effort, I conducted research on the effects of oxidative stress in a model of calpain activation due to glucose deprivation. Our findings suggest that the production of reactive oxygen species (ROS) mediated by NOX contributes to calpain activation, which is closely associated with neuronal death. My focus then shifted to characterizing the inflammatory mediators activated in response to excitotoxic damage. Through the use of a NOX-2 knockout mouse model, we found that the enzymatic activity of NOX-2 plays a crucial role in promoting a pro-inflammatory microglial phenotype that is strongly associated with neuronal death caused by excitotoxicity.