SP600125, a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson's disease，成果详细信息-中国科技论文在线

黎明涛

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期刊论文

SP600125, a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson's disease

黎明涛， Wenya Wang a ， Leyu Shi a ， b ， Yuanbin Xie b ， Chi Mab ， Wenming Li c ， Xingwen Su a ， Shoujian Huang a ， Ruzhu Chen a ， Zhenyu Zhu b ， Zixu Mao d ， Yifan Han c ， Mingtao Li a ， *

Neuroscience Research 48 (2004) 195～202，-0001，（）：

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摘要/描述

Increasing evidence suggests that c-Jun N-terminal kinase (JNK) is an important kinase mediating neuronal apoptosis in Parkinson's disease (PD) model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In order to study roles of JNK activity in neuronal apoptosis in this model, we blocked JNK activity in vivo using a specific inhibitor of JNK, SP600125. Our data showed that MPTP-induced phospho-c-Jun of substantial nigral neurons, caused apoptosis of dopaminergic neurons, and decreased the dopamine level in striatal area. We found that inhibiting JNK with SP600125 reduced the levels of c-Jun phosphorylation, protected dopaminergic neurons from apoptosis, and partly restored the level of dopamine in MPTP-induced PD in C57BL/6N mice. These results indicate that JNK pathway is the major mediator of the neurotoxic effects of MPTP in vivo and inhibiting JNK activity may represent a new and effective strategy to treat PD.

关键词: 1-Methyl-4-phenyl-1, ， 2, ， 3, ， 6-tetrahydropyridine ， SP600125 ， c-Jun N-terminal kinase ， Phospho-c-Jun ， Dopaminergic neurons ， Parkinson ， Mouse

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