权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

the role of molecular chaperones in α-synuclein-related diseases

分子伴侣在α-突触核蛋白相关疾病中的作用

基本信息

批准号：
15590887
负责人：
KAWAMOTO Yasuhiro
金额：
$ 2.24万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

14-3-3 proteins, a novel type of molecular chaperons, recognizes the phosphoserine-containing motifs of several target proteins, and regulates various types of signal transduction pathways. We have already reported that 14-3-3 immunoreactivity was localized to the α-synuclein-containing inclusins in brains with Parkinso's disease and multiple system atrophy. We then examined the brains and spinal cords of human α-synuclein (A53T) transgenic mice, and found the immunohistochemical colocalization of α-synuclein and 14-3-3 proteins. We also observed the increased immunoreactivities for some heat shock proteins in brains with synucleinopathies. Furthermore, we performed immunohistochemical studies on 14-3-3 proteins using autopsied spinal cord from patients with amyotrophic lateral sclerosis (ALS), and found 14-3-3 immunoreactivity in the Lewy body-like hyaline inclusions from both sporadic and familial ALS cases. We also observed that 14-3-3 immunoreactivity was localized to the α-synuclein-containing inclusinsin in the anterior horn cells from human SOD1(G93T) trausgenic mice. Moreover, we found the enhanced astroglial immunoexpression of 14-3-3 in the demyelinated lesions from patients with multiple sclerosis and progressive multifocal leukoencephalopathy, and in the cortical and subcortical lesions from patients with Creutzfeldt-Jakob disease, and in the ischemic white matter lesions from Binswanger's disease cases. These data suggest that 14-3-3 proteins may play an important role in the formation of several types of inclusions in brains with neurodegenerative diseases, and that 14-3-3 proteins may be induced in astrocytes under various kinds of pathological conditions, including demyelination, inflammation, and ischemia, and may be associated with the formation of astrogliosis.

14-3-3蛋白是一种新型分子伴侣蛋白，可识别多种靶蛋白的含磷酸丝氨酸基序，调控多种信号转导途径。我们已经报道了14-3-3免疫反应性局限于帕金森氏病和多系统萎缩的大脑中含有α-突触核蛋白的内含蛋白。然后，我们检测了人α-synuclein （A53T）转基因小鼠的大脑和脊髓，发现α-synuclein和14-3-3蛋白的免疫组织化学共定位。我们还观察到一些热休克蛋白在突触核蛋白病脑中的免疫反应性增加。此外，我们利用肌萎缩性侧索硬化症（ALS）患者的尸检脊髓对14-3-3蛋白进行了免疫组织化学研究，发现散发性和家族性ALS患者的路易体样透明包涵体中都存在14-3-3免疫反应性。我们还观察到14-3-3免疫反应性定位于人SOD1（G93T）致伤小鼠前角细胞中含有α-突触核蛋白的包含蛋白。此外，我们在多发性硬化症和进行性多灶性白质脑病患者的脱髓鞘病变、克雅氏病患者的皮质和皮质下病变以及Binswanger病患者的缺血性白质病变中发现14-3-3星形胶质细胞免疫表达增强。这些数据提示，14-3-3蛋白可能在神经退行性疾病大脑中多种类型包涵体的形成中发挥重要作用，并且在多种病理条件下，包括脱髓鞘、炎症、缺血，14-3-3蛋白可能在星形胶质细胞中被诱导，并可能与星形胶质增生的形成有关。