【摘 要】
：
帕金森病(Parkinsons disease,PD)是以中脑黑质多巴胺能神经元大量丢失为特征的第二大神经系统退行性疾病,异常的基因表达调控参与了多巴胺能神经元的改变过程.基因表达受转录因子调节,神经元限制性沉默因子(NRSF/REST)是一种锌指蛋白,通过组蛋白去乙酰化、染色质重塑、甲基化等机制能抑制一大类神经元专一性基因在非神经元细胞中的表达.NRSF和一种截短型的剪接体REST4在成体中枢神
【机 构】
：
复旦大学上海医学院医学神经生物学国家重点实验室,上海200032 中国科学院上海生命科学研究院生物
【出 处】
：
中国神经科学学会第四次会员代表大会暨第七届全国学术会议(The 7th Biennial Meeting and the
论文部分内容阅读
帕金森病(Parkinsons disease,PD)是以中脑黑质多巴胺能神经元大量丢失为特征的第二大神经系统退行性疾病,异常的基因表达调控参与了多巴胺能神经元的改变过程.基因表达受转录因子调节,神经元限制性沉默因子(NRSF/REST)是一种锌指蛋白,通过组蛋白去乙酰化、染色质重塑、甲基化等机制能抑制一大类神经元专一性基因在非神经元细胞中的表达.NRSF和一种截短型的剪接体REST4在成体中枢神经系统中仍有低水平的表达,REST4可以拮抗NRSF对其下游基因的沉默作用.我们用MPP+处理人多巴胺能细胞SH-SY5Y建立细胞PD模型,发现MPP+诱导后NRSF和REST4的表达和入核显著增加,而位于胞浆中的NRSF束缚蛋白Huntingtin以及一些下游基因,如酪氨酸羟化酶(TH)、脑源神经营养因子(BDNF)、SynapsinⅠ等却没有明显的改变,因此NRSF在帕金森病中的作用非常复杂.我们正利用已构建的慢病毒载体研究NRSF和REST4过表达和表达下调时对多巴胺能细胞存活的影响,并利用NRSF过表达、抑制和缺失的模式小鼠研究MPTP所致PD的病理进程和变化,最终阐明NRSF在PD中的作用和机制.
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