Indirubin-3'-monoxime is an effective inhibitor of cyclin-dependent protein kinases, and may play an obligate role in neuronal apoptosis in Alzheimer's disease. Here, we found that indirubin-3'-monoxime improved the morphology and increased the survival rate of SH-SY5Y cells exposed to amyloid-beta 25-35 (Aβ25-35), and also suppressed apoptosis by reducing tau phosphorylation at Ser199 and Thr205. Furthermore, indirubin-3'-monoxime inhibited phosphorylation of glycogen synthase kinase-3β (GSK-3β). Our results suggest that indirubin-3'-monoxime reduced Aβ25-35-induced apoptosis by suppressing tau hyperphosphorylation via a GSK-3β-mediated mechanism. Indirubin-3'-monoxime is a promising drug candidate for Alzheimer's disease.
Keywords: Alzheimer's disease; amyloid-beta; indirubin-3′-monoxime; nerve regeneration; neural regeneration; neuronal apoptosis; phosphorylated c-Jun N-terminal kinase; phosphorylated glycogen synthase kinase-3β; tau hyperphosphorylation.