Abstract
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 language | English |
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Pages (from-to) | 195-202 |
Number of pages | 8 |
Journal | Neuroscience Research |
Volume | 48 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Jan 2004 |
Externally published | Yes |
Keywords
- 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