中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (6): 988-993.doi: 10.4103/1673-5374.184500

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

3’单肟靛玉红抑制tau蛋白过度磷酸化可减轻Aβ诱导神经元的凋亡

  

  • 收稿日期:2016-04-12 出版日期:2016-06-30 发布日期:2016-06-30
  • 基金资助:

    南京市医学科技发展基金(QRX11199),南京市科技局项目(201303010),南京市卫生研究项目(YKK14101)

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

Shu-gang Zhang1, #, Xiao-shan Wang1, #, Ying-dong Zhang1, 2, *, Qing Di1, Jing-ping Shi1, Min Qian1, Li-gang Xu1, Xing-jian Lin1, Jie Lu1   

  1. 1 Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China 2 Department of Neurology, Affiliated Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
  • Received:2016-04-12 Online:2016-06-30 Published:2016-06-30
  • Contact: Ying-dong Zhang, M.D., zhangyingdong@aliyun.com.
  • Supported by:

    This research was supported by the Nanjing Medical Science and Technique Development Foundation of China, No. QRX11199; a grant from the Nanjing Science and Technology Commission Project of China, No. 201303010; and a grant from the Health Research Project in Nanjing City of China, No. YKK14101.

摘要:

3’单肟靛玉红是细胞周期依赖性蛋白激酶的一种有效抑制剂,可能参与阿尔茨海默病神经元凋亡的进程。在实验结果中发现,3’单肟靛玉红能改善Aβ25-35损伤的SH-SY5Y 细胞的形态及存活率,还能通过逆转tau蛋白Ser-199和Thr-205位点磷酸化水平而抑制神经元凋亡,通过抑制GSK3β磷酸化而降低tau蛋白的磷酸化水平。结果提示3’单肟靛玉红通过抑制tau蛋白过度磷酸化减轻了Aβ诱导的神经元凋亡,有望成为治疗阿尔茨海默病的有效药物。

orcid: 0000-0002-6470-5064 (Ying-dong Zhang)

关键词: 神经再生, 3’单肟靛玉红, Aβ, 阿尔茨海默症, 细胞凋亡, Tau蛋白过度磷酸化, 磷酸化GSK3β, 磷酸化JNK

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