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

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 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

• 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