Fig. 3

Dysregulation of PI3K-AKT signaling causes abnormal microglial responses and promotes neuronal damage and chronic neuroinflammation. Resting microglia undergo activation upon encountering stimuli in their environment, triggering the release of nitric oxide and the coordinated expression of pro- and anti-inflammatory cytokines to clear the stimulus and promote recovery. Under normal conditions, PI3K-AKT signaling is terminated, the microglial response subsides and neurons are preserved. However, in certain settings, PI3K-AKT signaling is sustained, microglial responses persist perpetuating the release of pro-inflammatory cytokines into the brain microenvironment, which damages healthy neurons and contributes to progressive neurodegeneration