Abstract:

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 SHSY5Y 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.

Key words: nerve regeneration, indirubin-3′-monoxime, amyloid-beta, Alzheimer’s disease, neuronal apoptosis, tau hyperphosphorylation, phosphorylated glycogen synthase kinase-3β, phosphorylated c-Jun N-terminal kinase, neural regeneration