摘要 : Increasing evidence suggests that inflammation may be involved in the loss of dopaminergic neurons in Parkinson's disease (PD). Among inflammatory molecules, COX-2, a key kinase for the inflammatory response, has been suggested to... 展开 Increasing evidence suggests that inflammation may be involved in the loss of dopaminergic neurons in Parkinson's disease (PD). Among inflammatory molecules, COX-2, a key kinase for the inflammatory response, has been suggested to play an important role in dopaminergic neuron loss in PD. However, the upstream molecular pathways of COX-2 expression remain uncertain. In the present study, we investigated the role of c-Jun [1] N-terminal kinase (JNK) in the process of COX-2 expression in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of subacute PD. Our data showed that MPTP induced a transient JNK activation of dopaminergic neurons, upregulated COX-2 expression in dopaminergic neurons, and caused the loss of dopaminergic neurons. We found that inhibiting JNK with SP600125, a special inhibitor of JNK, reduced the levels of c-Jun phosphorylation, blocked p-c-Jun translocation from the cytoplasm to the nucleus in dopaminergic neurons of substantia nigra, mitigated the loss of dopaminergic neurons, and improved motor function in MPTP-induced PD in C57BL/6N mice. These results indicate that JNK signaling pathway may be the major upstream mediator of regulation of COX-2 expression induced by MPTP in vivo and inhibiting JNK activity may represent a new and effective strategy to PD. 收起