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

• Main Authors: Shu-gang Zhang, Xiao-shan Wang, Ying-dong Zhang, Qing Di, Jing-ping Shi, Min Qian, Li-gang Xu, Xing-jian Lin, Jie Lu
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2016-01-01
• Series: Neural Regeneration Research
• Subjects: 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
• Online Access: http://www.nrronline.org/article.asp?issn=1673-5374;year=2016;volume=11;issue=6;spage=988;epage=993;aulast=Zhang

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.