Indirubin-3'-monoxime inhibits beta-amyloid-induced neurotoxicity in neuroblastoma SH-SY5Y cells.
Increasing evidence suggests that the inappropriate activation of cyclin-dependent kinases (CDKs) could induce neuronal apoptosis in Alzheimer's disease (AD), which means that the pharmacological inhibitors of cell-cycle progression may effectively impede the development or progression of AD. Indirubin-3'-monoxime (IMX), a known effective inhibitor of CDKs, has been shown to have therapeutic effects on learning and memory deficits induced by beta-amyloid (Abeta) intracerebroventricular infusion in rats. In the present study, we investigated the neuroprotective effects of IMX on Abeta(25-35)-induced neuronal apoptosis and its potential mechanisms in human neuroblastoma SH-SY5Y cells. Abeta(25-35)-induced apoptosis, characterized by decreased cell viability, neuronal DNA condensation, and fragmentation, was associated with an increase in tau protein hyperphosphorylation. IMX, however, attenuated Abeta(25-35)-induced cell death in a dose-dependent manner. Furthermore, expression of hyperphosphorylation tau protein was significantly decreased with IMX treatment. Our study suggests that IMX may usefully prevent or delay the neuronal loss of AD.
Zhang
Shugang
S
Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, 264 Guangzhou Road, Nanjing, Jiangsu Province 210029, PR China.
Zhang
Yingdong
Y
Xu
Ligang
L
Lin
Xingjian
X
Lu
Jie
J
Di
Qing
Q
Shi
Jingping
J
Xu
Jun
J
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D017302:Annexins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000494:pharmacology*; D009447:Neuroblastoma / Q000473:pathology; D010091:Oximes / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012694:Serine / Q000378:metabolism; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D017302:Annexins; D007211:Indoles; D010091:Oximes; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C474021:indirubin-3'-monoxime; D016875:tau Proteins; D012694:Serine