Nesfatin-1是胃底X/A细胞分泌的一种能自由通过血脑屏障的脑肠肽。我们前期工作表明nesfatin-1通过激活C-Raf/ERK途径对MPTP制备的帕金森病（PD）小鼠发挥保护作用，但nesfatin-1在黑质多巴胺（DA）能神经元上的受体至今未见报道。有研究提示黑皮质素4受体（MC4R）可能是nesfatin-1受体之一。为深入阐明nesfatin-1神经保护作用机制，本研究拟首先在PD细胞模型和PD转基因小鼠黑质上观察nesfatin-1与MC4R的结合情况，及C-Raf/ERK/CREB通路的激活与nesfatin-1保护作用的相关性；慢病毒沉默MC4R和CREB后，再观察nesfatin-1保护作用的改变。本研究有望首次鉴定出DA能神经元上nesfatin-1的受体MC4R，并阐明MC4R激活的C-Raf/ERK/CREB通路在nesfaitn-1保护DA能神经元中的作用。

Nesfatin-1 is a brain-gut peptide secreted by X/A like endocrine cells in the gastric glands, which could crosses the blood-brain barrier freely. Our previous study showed that nesfatin-1 protected dopaminergic neurons against MPTP induced neurotoxicity through the C-Raf/ERK-dependent anti-apoptotic pathway. But the receptor of nesfatin-1 on dopaminergic neurons in substantia nigra remains unknown. It has been reported that melanocortin 4 receptor（MC4R） is the possible receptor of nesfatin-1. In order to elucidate the receptor of nesfatin-1 on dopaminergic neurons and mechanisms underlying the protective effect, PD cell model and PD transgenic mice will be employed to observe the interaction between nesfaitn-1 and MC4R in substantia nigra, and the C-raf/ERK/CREB signaling pathway alteration induced by nesfatin-1. The alteration of the protective effect of nesfatin-1 on dopaminergic neurons will be further observed in MC4R or CREB silenced PD models to demonstrated that MC4R is the receptor of nesfatin-1 on dopaminergic neurons, and the protective effect of nesfatin-1 on dopaminergic neurons is mediated by C-Raf/ERK/CREB signaling pathway through MC4R.