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Title: Inhibition of glycogen synthase kinase-3 beta protects doparninergic neurons from MPTP toxicity
Author: Wang, Wenya ; Yang, Yi ; Ying, Chunyi ; Li, Wenming ; Ruan, Haolan ; Zhu, Xiaonan ; You, Yan ; Han, Yifan ; Chen, Ruzhu ; null(王以政) ; Li, Mingtao
Source: NEUROPHARMACOLOGY
Issued Date: 2007
Volume: 52, Issue:8, Pages:1678-1684
Keyword: GSK-3 beta ; indirubin-3'-oxime ; AR-A014418 ; dopaminergic neurons ; MPTP ; Parkinson's disease ; PARKINSONS-DISEASE ; DOPAMINERGIC-NEURONS ; ALZHEIMERS-DISEASE ; KINASE 3-BETA ; TAU-PROTEIN ; SWIM-TEST ; MOUSE ; PHOSPHORYLATION ; MODEL ; MICE
Subject: Neurosciences & Neurology ; Pharmacology & Pharmacy
Corresponding Author: Li, MT (reprint author), Sun Yat Sen Univ, Zhong Sch Med, Inst Clin Pharmacol, Guangzhou 510515, Guangdong, Peoples R China,limt@mail.sysu.edu.cn
English Abstract: Glycogen synthase kinase-3 beta (GSK-3 beta) is closely involved in neuronal apoptosis and pathogenesis of many neurodegenerative diseases, such as Alzheimer's disease. However, whether GSK-3 beta mediates apoptosis of dopaminergic neurons in Parkinson's disease remains elusive. In this study, using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism models, we investigated whether MPTP induces apoptosis of dopaminergic neurons through a GSK-3 beta-dependent pathway. MPTP caused a rapid activation of GSK-3 beta, evidenced by the decrease in level of phospho-Ser9 of GSK-3 beta and the increase in level of phospho-Ser396 of tau, a known GSK-3 beta substrate. Blockage of GSK-3 beta activity by its two specific inhibitors, indirubin-3'-oxime and AR-A014418, prevented dopaminergic neurons from MPTP-induced apoptosis. Additionally, inhibition of GSK-3 beta activity restored the depletion of striatal dopamine and ameliorated behavioral impairments caused by MPTP. These results indicate that GSK-3 beta is a critical intermediate of MPTP neurotoxicity, and inhibition of GSK-3 beta may provide a novel strategy to treat Parkinson's disease. (c) 2007 Elsevier Ltd. All rights reserved.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1770
Appears in Collections:神经所(总)_期刊论文
神经信号转导研究组_期刊论文

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Wang, Wenya; Yang, Yi; Ying, Chunyi; Li, Wenming; Ruan, Haolan; Zhu, Xiaonan; You, Yan; Han, Yifan; Chen, Ruzhu; Wang, Yizheng; Li, Mingtao.Inhibition of glycogen synthase kinase-3 beta protects doparninergic neurons from MPTP toxicity,NEUROPHARMACOLOGY,2007,52(8):1678-1684
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