Nesfatin-1 protects dopaminergic neurons against MPP(+)/MPTP-induced neurotoxicity through the C-Raf-ERK1/2-dependent anti-apoptotic pathway.
Nesfatin-1 protects dopaminergic neurons against MPP(+)/MPTP-induced neurotoxicity through the C-Raf-ERK1/2-dependent anti-apoptotic pathway.
复制标题
NESFATIN-1通过C-RAF-ERK1/2依赖性抗凋亡途径保护多巴胺能神经元免受MPP（+）/MPTP诱导的神经毒性。
DOI：
10.1038/srep40961
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发表时间：
2017-01-20
影响因子：
4.6
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Shen XL;Song N;Du XX;Li Y;Xie JX;Jiang H
据报道，几种脑肠肽与中枢多巴胺能系统有密切的关系，其中一种脑肠肽是Nesfatin-1。Nesfatin-1是一种饱满肽，主要由胃腺中类似X/A的内分泌细胞分泌，胃促生长素也在胃腺中分泌。我们先前报道了Ghrelin对黑质多巴胺能神经元的神经保护作用，这暗示了Ghrelin在帕金森病(PD)中的作用。在目前的研究中，我们的目的是阐明Nesfatin-1在体内和体外对多巴胺能神经元是否具有类似的作用。在1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)诱导的帕金森病小鼠模型中，Nesfatin-1减轻了黑质多巴胺能神经元的丢失。此外，在1-甲基-4-苯基吡啶离子(MPP+)诱导的MES23.5多巴胺能细胞中，Nesfatin-1通过恢复线粒体功能、抑制细胞色素C的释放和阻止caspase-3的激活而拮抗MPP+诱导的毒性。这些神经保护作用可被选择性抑制C-Raf和细胞外信号调节蛋白激酶1/2(ERK1/2)所消除。我们的数据表明，C-Raf-ERK1/2参与了抗凋亡途径，在MPTP诱导的毒性背景下，Nesfatin-1的神经保护作用是负责的。这些结果提示Nesfatin-1可能对帕金森病有治疗潜力。
Several brain-gut peptides have been reported to have a close relationship with the central dopaminergic system; one such brain-gut peptide is nesfatin-1. Nesfatin-1 is a satiety peptide that is predominantly secreted by X/A-like endocrine cells in the gastric glands, where ghrelin is also secreted. We previously reported that ghrelin exerted neuroprotective effects on nigral dopaminergic neurons, which implied a role for ghrelin in Parkinson’s disease (PD). In the present study, we aim to clarify whether nesfatin-1 has similar effects on dopaminergic neurons both in vivo and in vitro. We show that nesfatin-1 attenuates the loss of nigral dopaminergic neurons in the 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. In addition, nesfatin-1 antagonized 1-methyl-4-phenylpyridillium ion (MPP+)-induced toxicity by restoring mitochondrial function, inhibiting cytochrome C release and preventing caspase-3 activation in MPP+-treated MES23.5 dopaminergic cells. These neuroprotective effects could be abolished by selective inhibition of C-Raf and the extracellular signal-regulated protein kinase 1/2 (ERK1/2). Our data suggest that C-Raf-ERK1/2, which is involved in an anti-apoptotic pathway, is responsible for the neuroprotective effects of nesfatin-1 in the context of MPTP-induced toxicity. These results imply that nesfatin-1 might have therapeutic potential for PD.