title: Indirubin-3'-monoxime inhibits beta-amyloid-induced neurotoxicity in neuroblastoma SH-SY5Y cells.
abstract: 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.
authors.affiliation: Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, 264 Guangzhou Road, Nanjing, Jiangsu Province 210029, PR China.
authors.forename: Shugang
authors.initials: S
authors.lastname: Zhang
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ligang
authors.initials: L
authors.lastname: Xu
authors.forename: Xingjian
authors.initials: X
authors.lastname: Lin
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Qing
authors.initials: Q
authors.lastname: Di
authors.forename: Jingping
authors.initials: J
authors.lastname: Shi
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
mesh_terms: 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
chemical_list: 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