线粒体未折叠蛋白反应（mtUPR）是线粒体蛋白质量控制（PQC）体系的第一道防线，它是最早发生的线粒体保护反应。 越来越多的证据表明，mtUPR直接或间接地参与了神经变性疾病的发生和发展，近年来mtUPR在PD中的角色逐渐显现，然而以往的研究过程大多集中在蠕虫和酵母。本研究选用SH-SY5Y细胞体系以及健康雄性C57BL小鼠建立PD的细胞以及动物模型，通过分子克隆技术、目标基因过表达、RNA干扰、免疫荧光、激光共聚焦、CRISPR基因编辑、光遗传学等技术，全面了解多巴胺能神经元在不同刺激条件下mtUPR的激活情况，探讨何种线粒体-核间mtUPR的信号转导在多巴胺能神经元中占据主导机制，并对SIRT家族介导的转录因子途径在帕金森病多巴胺能神经元中是否正性调节mtUPR活性进行研究。研究结果将为PD等神经退行性病变如何尽早调节线粒体稳态平衡的未来干预目标提供重要思路。

The mitochondrial unfolded protein response (mtUPR) is the first defense line of mitochondrial protein quality control (PQC) system, it is the earliest occurrence of mitochondrial protective reaction. More and more evidence shows that mtUPR, directly or indirectly involved in the occurrence and development of neurodegenerative diseases, the role of mtUPR in PD appears gradually in recent years. However past research mostly concentrated in worms and yeast. The system of SH-SY5Y cells and healthy male C57BL mice are selected to establish PD cellular and animal models.The methods of molecular cloning technique, RNA interference, immunofluorescence and laser confocal, CRISPR gene editing, optogenetics technology will be used. The purpose of this study is to comprehensively understand the mtUPR activation of dopaminergic neurons in different conditions, which signal transduction between the mitochondrial and nuclear mtUPR in dopaminergic neurons occupy a dominant mechanism, and whether the SIRT family mediated transcription factor pathways in dopamine neurons positively regulate the activity of mtUPR. The research results will provide important ideas to regulate mitochondrial homeostasis for the future intervention targets PD and other neurodegenerative diseases.