Indirubin-3'-monoxime rescues spatial memory deficits and attenuates β-amyloid-associated neuropathology in a mouse model of Alzheimer's disease

Abstract Indirubin and its derivatives have been shown to possess potent inhibitory effects on cyclin-dependent protein kinase 5 and glycogen synthase kinase 3β, two protein kinases involved in abnormal hyperphosphorylation of tau and amyloid precursor protein processing/β-amyloid (Aβ) production. Here, we showed that systemic treatment of APP and presenilin 1 (PS1) transgenic mice, a robust Alzheimer's disease (AD) mouse model, with indirubin-3'-monoxime (IMX; 20 mg/kg; 3 times weekly), for as little as 2 months, significantly attenuated spatial memory deficits. This was accompanied by a marked decrease in several AD-like phenotypes, including Aβ deposition, tau hyperphosphorylation, accumulation of activated microglia and astrocytes around Aβ plaques, and loss of synaptophysin immunoreactivity. These findings suggest that IMX is a potential therapeutic agent to combat AD.