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

Wenya Wang, Leyu Shi, Yuanbin Xie, Chi Ma, Wenming Li, Xingwen Su, Shoujian Huang, Ruzhu Chen, Zhenyu Zhu, Zixu Mao, Yifan Han, Mingtao Li

Research output: Journal article publicationJournal articleAcademic researchpeer-review

138 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)195-202
Number of pages8
JournalNeuroscience Research
Issue number2
Publication statusPublished - 1 Jan 2004
Externally publishedYes


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

ASJC Scopus subject areas

  • General Neuroscience


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