PINK1分子介导的线粒体融合蛋白Mfn2泛素化降解在铅污染致小鼠神经干细胞损伤中的作用及机制研究

铅污染是我国乃至世界范围内普遍存在的环境问题，并严重影响人类健康。铅对神经系统损伤尤为严重，但铅诱导神经系统损伤的机制尚未阐明。我们的前期结果发现，铅诱导神经干细胞损伤是其神经毒性的主要诱因，因此探究神经干细胞损伤的分子机制对防治铅污染对健康的影响具有重要的意义。我们的课题拟从铅暴露后神经干细胞线粒体形态功能紊乱这一前期结果着手，以研究MFN2分子在线粒体形态功能紊乱中发挥的作用为宗旨，以探寻E3连接酶PINK1诱导MFN2分子泛素化降解的机制为目标，最终阐明内质网-线粒体交互作用在铅诱导神经干细胞损伤中的重要机制。研究结果对于深层次认识铅损伤神经系统的机制，寻找有效防治铅污染健康危害，将会有重要的理论和实际意义。

Lead pollution has been a common environmental issue seriously affecting human health in China and the world. Lead particularly damages nervous system, but its inducing mechanism has not been clarified. According to our previous studies, nervous system impairment is the main aspect showing the neurotoxicity of lead. Therefore, exploration on the molecular mechanism of neural stem cells impairment is significant to the prevention of lead pollution to human health. By following previous research results, our study started from the morphological dysfunction of mitochondria of neural stem cell in lead exposure, aiming to find out the function of MFN2 in the whole process and the mechanism of PINK-induced Mfn2 degradation by ubiquitination, so as to explain the mechanism of endoplasmic reticulum-mitochondrion interaction in the lead-induced neural stem cells impairment. The study results will be of great theoretical and practical significance to in-depth understanding of the mechanism of lead-induced nervous system impairment and effective controlling measures exploration to lead pollution.