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Studies on the practical diagnosis and pathomechanism of tauopathy as neurodegenerative disordrs

神经退行性疾病 tau 蛋白病的实际诊断和病理机制研究

基本信息

批准号：
16590848
负责人：
MORI Hideo
金额：
$ 2.18万
依托单位：
Juntendo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

1)Based on the analysis of the clinical, pathological and genetic features of the three families with tau N279K mutation, we have demonstrated that the clinical phenotype of N279K mutation was relatively uniform even in the families with unrelated founders. The pathologic changes involved the spinal cord as well as basal ganglia, and cerebral cortex and white matter.2)We have retrospectively reviewed 8 patients with autopsy-proven corticobasal degeneration and reported the variable clinical phenotypes including marked palilalia, progressive dysarthria, progressive dysphagia, and non-fluent aphasia.3)We transiently transfected mouse neuroblastoma cells (N18TG2) with wild-type tau or tau with the L266V mutation from a patient with familial frontotemporal dementia. Tau protein was observed in both the wild-type and L266V mutant tau transfectants, as were inclusions composed of tau phosphorylated at amino acids Thrl 81, Ser 202/Thr205, and Ser396. Inclusions immunoreactive with anti-tau antibodies AT8 and pS396 were also immunoreactive with antibodies against ubiquitin and glycogen synthase kinase 3□.4)We have revealed that progression of motor deterioration in the model mice with P301 tau mutation was inhibited by administration of lithium.

1)通过对三个tau N279K突变家系的临床、病理和遗传学特征的分析，发现即使在无血缘关系的家系中，N279K突变的临床表现也较为一致。病理改变累及脊髓和基底节，以及大脑皮质和白质2)我们回顾了8例尸检证实的皮质基底膜变性患者，并报告了不同的临床表型，包括明显的下睑、进行性构音障碍、进行性吞咽困难和非流利性失语。3)我们瞬时地将野生型tau或带有L266V突变的tau基因的小鼠神经母细胞瘤细胞(N18TG2)从家族性额颞叶痴呆患者中导入。野生型和L266V突变型tau转染体中均观察到tau蛋白，包涵体是由Thr1 81、Ser202/Thr205和Ser396位氨基酸磷酸化的tau包涵体。与抗tau抗体AT8和pS396免疫反应的包涵体也与抗泛素和糖原合成酶激酶3-抗体呈免疫反应。4)我们发现服用锂可以抑制P301 tau突变模型小鼠的运动恶化进程。

项目成果

期刊论文数量（64）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Pathologic changes of progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy : Prototype and clinicopathological diversity.

进行性核上性麻痹、皮质基底节变性和多系统萎缩的病理变化：原型和临床病理学多样性。

DOI：
发表时间：
2006
期刊：
J Neurol 253・Suppl 3
影响因子：
0
作者：
Sato K;Hatano T;Yamashiro K;Kagohashi M;Nishioka K;Izawa N;Mochizuki H;Hattori N;Mori H;Mizuno Y;Mori H.
通讯作者：
Mori H.

Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein

Sept4 是突触前支架和路易体的组成部分，是抑制 α-突触核蛋白所必需的