【摘 要】
：
帕金森病(Parkinson,s Disease,PD)是一种中老年人常见的神经系统变性疾病,病理上主要表现为黑质(Substantia nigra)多巴胺(dopamine,DA)能神经元的丢失以及路易小体(Lewy Body)的形成.微管相关蛋白(Microtubule Associated Protein,MAPs)的非正常累积和聚集在神经变性疾病的发病中起到了重要作用.DJ-1/Park7
【机 构】
：
中国科学院上海生命科学研究院/上海交通大学医学院健康科学研究所,上海200025 中国科学院上海生
【出 处】
：
中国神经科学学会第九届全国学术会议暨第五届会员代表大会
论文部分内容阅读
帕金森病(Parkinson,s Disease,PD)是一种中老年人常见的神经系统变性疾病,病理上主要表现为黑质(Substantia nigra)多巴胺(dopamine,DA)能神经元的丢失以及路易小体(Lewy Body)的形成.微管相关蛋白(Microtubule Associated Protein,MAPs)的非正常累积和聚集在神经变性疾病的发病中起到了重要作用.DJ-1/Park7的缺失性突变能够引起早发的家族性PD.DJ-1作为分子伴侣可以抑制α-synuclein的聚集.目前尚不清楚D J-1是否也可以调控MAPs的非正常聚集,以及与此相关的在帕金森病发病中的机制.本实验通过GST亲和层析以及免疫共沉淀实验表明D J-1可以与微管相关蛋白1b的轻链(Microtubule associated protein 1b Light Chain, MAP1b-LC)结合.Western blot及免疫荧光实验表明过表达DJ-1可以在SH-SY5Y或Hek293t细胞中抑制MAP1b-LC的聚集(aggregation).在SH-SY5Y细胞中通过RNA干扰降低DJ-1的表达则可以增加MAP1b-LC的聚集.在D J-1基因敲除小鼠脑中的不可溶MAP1 b-LC的含量增加.更重要地,在DJ-1 Knocking down (KD)的SH-SY5Y的细胞中,过表达MAP1 b-LC可以引发内质网应激诱发的细胞凋亡.我们的结果表明DJ-1可以起到分子伴侣的功能来抑制MAP1 b-LC的聚集以及其引发的细胞凋亡,这为进一步地了解DJ-1的生物学特征以及PD的发病机制提供了新的视野.
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