基于MC1R探讨熟地平颤方对帕金森病与黑色素瘤“异病同治”的分子机理

以脑内黑质多巴胺神经元过早死亡为特征的帕金森病（PD）和以外周黑素细胞过度增殖为标志的黑色素瘤（MM）具有交互发病风险。多巴胺神经元与黑素细胞同为色素细胞，都使用左旋多巴合成多巴胺和色素。最新研究表明，色素基因MC1R或为PD与MM的共同遗传因素对多巴胺系统具有与黑素细胞类似的由色素介导的调控作用。而α-突触核蛋白（α-syn）作为两者共同的病理基础，是否由MC1R调控目前尚不清楚。课题组前期研究发现组成神经黑色素中的褐黑素会诱导α-syn的过表达增加其寡聚化和纤维化造成神经元死亡，熟地平颤方对于褐黑素介导的α-syn过表达及异常聚集均有抑制作用。本课题拟在前期基础上提出科学假说：MC1R介导的色素通路失调导致α-syn异常聚集是促进PD-MM发生发展的共同机制；熟地平颤方通过上调MC1R表达延缓PD及MM的病情进展，发挥“异病同治”作用。推动PD与MM共同发病因素的跨学科研究。

Parkinson's disease(PD), characterized by premature death of dopaminergic neurons in the substantia nigra are at risk of interaction with melanoma(MM), which is marked by hyperproliferation of peripheral melanocytes. Both dopaminergic neurons and melanocytes are pigment cells, which use levodopa to synthesize dopamine and pigment. According to recent studies, chromogene MC1R might be the common genetic factor of PD and MM and play a regulative role in dopamine system following a melanocyte-like pigment-mediated pattern. However, it remains unclear whether α- synaptic nucleoprotein(α-syn), the common pathological factor of PD and MM, is regulated by MC1R. The previous study of the research group found that the pheomelanin in the neuromelanin can induce the over expression of α - synuclein, increase the oligomerization of α - syn and cause neuron death due to fibrosis, and that ShuDiPingChan prescription can inhibit both over expression and abnormal aggregation of α - syn mediated by pheomelanin. On the basis of previous studies, we put forward the following hypotheses that the abnormal aggregation of α - syn, resulted by imbalance of MC1R regulated pigment pathway, is the common mechanism of PD-MM association and progression, and that ShuDiPingChan prescription can delay the progress of PD and MM by improving MC1R function, playing the role of "same treatment for different diseases". The study is designed to promote interdisciplinary researches in common pathological factors of PD and MM.