脑多巴胺D2受体介导的CYP/ciRS-7/miR-7信号轴在PD模型中调控α-SYN聚集的作用及机制研究

α-synuclein (α-SYN) aggregation is a key step in the pathogenesis of parkinson's disease (PD). Studies have shown that cholesterol metabolism catalyzed by the cytochrome P450 enzyme (CYP) is involved in the regulation of α-SYN aggregation. Our previous studies showed that dopamine D2 receptor (DRD2) regulates brain cholesterol metabolism-related CYP expression, and ciRS-7/miR-7 system is associated with abnormal aggregation of α-SYN. Based on the existing work, we intend to elucidate the regulatory mechanism of DRD2 on CYP by using a variety of techniques such as analytical chemistry, molecular biology and genetic engineering, and further explore how brain CYP can alter ciRS-7/miR-7 system in order to elucidate the regulatory mechanism of DRD2-mediated CYP/ciRS-7/miR-7 signal axis on α-SYN aggregation. The research will clarify the change rules of brain CYP-dependent regulation axis in PD and the transduction of pathological information, and expand the understanding of pathological mechanism of PD from different perspectives such as metabolism, gene, protein and animal and provide ideas for the early warning and treatment of PD.

α-突触核蛋白(α-SYN)的聚集是帕金森病(PD)发病的关键步骤。研究表明，脑细胞色素 P450酶系(CYP)催化的胆固醇代谢参与α-SYN聚集的调控。本课题组前期研究表明多巴胺D2受体(DRD2)可调控脑胆固醇代谢相关CYP的表达，并且ciRS-7/miR-7系统与α-SYN的异常聚集相关。本课题组在已有的工作基础上，拟采用分析化学、分子生物学、基因工程等多种技术手段阐明DRD2对CYP的调控机制，并进一步探讨脑CYP如何通过影响胆固醇的代谢而改变ciRS-7/miR-7系统的活性，试图阐明DRD2介导的CYP/ciRS-7/miR-7信号轴对α-SYN聚集的调控机制。研究将明确脑CYP依赖性调控轴在PD中的变化规律以及病理信息转导作用，从代谢、基因、蛋白、整体动物等不同角度拓展对PD病理机制的认识，为PD的预警及治疗提供思路。

α-突触核蛋白(α-SYN)的聚集是帕金森病(PD)发病的关键步骤。研究表明，脑细胞色素 P450酶系(CYP)催化的胆固醇代谢参与α-SYN聚集的调控。本课题组前期研究表明多巴胺D2受体(DRD2)可调控脑胆固醇代谢相关CYP的表达，并且ciRS-7/miR-7系统与α-SYN的异常聚集相关。本课题组在已有的工作基础上，采用分析化学、分子生物学、基因工程等多种技术手段阐明DRD2对CYP的调控机制，并进一步探讨脑CYP如何通过影响胆固醇的代谢而改变ciRS-7/miR-7系统的活性，阐明了DRD2介导的CYP/ciRS-7/miR-7信号轴对α-SYN聚集的调控机制。研究将明确脑CYP依赖性调控轴在PD中的变化规律以及病理信息转导作用，从代谢、基因、蛋白、整体动物等不同角度拓展对PD病理机制的认识，为PD的预警及治疗提供思路。