GSK3 inhibitors show benefits in an Alzheimer's disease (AD) model of neurodegeneration but adverse effects in control animals

The dysregulation of glycogen synthase kinase-3 (GSK3) has been implicated in Alzheimer disease (AD) pathogenesis and in Aβ-induced neurotoxicity, leading us to investigate it as a therapeutic target in an intracerebroventricular Aβ infusion model. Infusion of a specific GSK3 inhibitor SB216763 (SB) reduced a downstream target, phospho-glycogen synthase 39%, and increased glycogen levels 44%, suggesting effective inhibition of enzyme activity....