Indirubin-3′-monoxime suppresses amyloid-beta-induced apoptosis by inhibiting tau hyperphosphorylation

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 SHSY5 Y 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.