SP600125, a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson’s disease
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- 作者：Wang ; Wenya ; Shi ; Leyu ; Xie ; Yuanbin ; Ma ; Chi ; Li ; Wenming ; Su ; Xingwen ; Huang ; Shoujian ; Chen ; Ruzhu ; et. al.
- 关键词：JNK ; c-Jun N-terminal kinase ; TH ; tyrosine hydroxylase ; MPTP ; 1-methyl-4-phenyl-1 ; 2 ; 3 ; 6-tetrahydropyridine ; SNc ; substantia nigra pars compacta ; PD ; Parkinson’ ; s disease ; PFA ; paraformaldehyde ; DAB ; diaminobenzidine ; JBD ; JNK binding domain ; JIP-1 ; JN
- 刊名：Neuroscience Research
- 出版年：2004
- 出版时间：February, 2004
- 年：2004
- 卷：48
- 期：2
- 页码：195-202
- 全文大小：384 K
文摘
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.