Curcumin inhibition of JNKs prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease through suppressing mitochondria dysfunction.
Curcumin inhibition of JNKs prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease through suppressing mitochondria dysfunction.
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DOI：
10.1186/2047-9158-1-16
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发表时间：
2012-08-20
影响因子：
12.6
通讯作者：
Chen SD
中科院分区：
文献类型：
--
作者：
Pan J;Li H;Ma JF;Tan YY;Xiao Q;Ding JQ;Chen SD
姜黄素是一种从姜黄中提取的天然多酚，它在多种神经退行性疾病中具有神经保护作用，尽管其机制仍知之甚少。我们最近的实验结果表明，姜黄素可以保护帕金森病 (PD) 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 小鼠模型中的多巴胺能神经元免于凋亡。在 MPTP 小鼠模型中，姜黄素显着抑制纹状体中多巴胺能神经元的死亡和多巴胺能轴突的损失。进一步的研究表明姜黄素抑制 MPTP 处理诱导的 JNK 过度磷酸化。 JNK 磷酸化可导致 Bax 易位至线粒体并释放细胞色素 c，最终导致线粒体介导的细胞凋亡。姜黄素可以减弱这些促凋亡作用。我们的实验表明，姜黄素可以通过抑制 MPTP 诱导的 JNK 过度磷酸化来抑制线粒体功能障碍，从而预防黑质纹状体变性。我们的结果表明 JNKs/线粒体通路可能是治疗 PD 患者的新靶点。
Curcumin,a natural polyphenol obtained from turmeric,has been implicated to be neuroprotective in a variety of neurodegenerative disorders although the mechanism remains poorly understood. The results of our recent experiments indicated that curcumin could protect dopaminergic neurons from apoptosis in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). The death of dopaminergic neurons and the loss of dopaminergic axon in the striatum were significantly suppressed by curcumin in MPTP mouse model. Further studies showed that curcumin inhibited JNKs hyperphosphorylation induced by MPTP treatment. JNKs phosphorylation can cause translocation of Bax to mitochondria and the release of cytochrome c which both ultimately contribute to mitochondria-mediated apoptosis. These pro-apoptosis effect can be diminished by curcumin. Our experiments demonstrated that curcumin can prevent nigrostriatal degeneration by inhibiting the dysfunction of mitochondrial through suppressing hyperphosphorylation of JNKs induced by MPTP. Our results suggested that JNKs/mitochondria pathway may be a novel target in the treatment of PD patients.