The Study concerning the pathogenesis of non-Alzheimer neurodegenerative dementias from the perspective of abnormal cytoskeletons

从异常细胞骨架角度探讨非阿尔茨海默型神经退行性痴呆发病机制

• 批准号: 12670952
• 负责人: ISEKI Eizo
• 金额: $ 2.11万
• 依托单位: Yokohama City University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670952/
• 关键词: dementia with Lewy bodies; Lewy body; α-synuclein; phosphorylated raw; frontotemporal; Pick's disease; ubiquitin; 皮質基底核変性症; 進行性核上性麻痺; シンフィリン-1; タウ; 無性; 遺伝子異常; 診断基準; 細胞骨格

The study concerning the pathogenesis of non-Alzheimer neurodegenerative dementias has been performed from the perspective of abnormal cytoskeletons. Cytopathological and clinicopathological studies of dementia with Lewy bodies (DLB) have been focused. In the cytopathological studies, formation process or degeneration process of Lewy bodies was investigated using α-synuclein immunohistochemistry. Lewy bodies were formed by the accumulation of α-synuclein in the abnormal cytoskeletons with axonal transport blockage, and degenerated with glial and immunological reaction. In the clinicopathological studies, Lewy pathology was graded from stage I to stage IV, and autopsied cases of DLB were classified into some subtypes according to the degree of Lewy pathology or Alzheimer pathology. In frontotemporal dementia (FTD), Pick's disease (PiD) was divided into two types of tauopathy and ubiquitinopathy.

从细胞骨架异常的角度对非阿尔茨海默病的发病机制进行了研究。路易体痴呆的细胞病理学和临床病理研究一直是研究的热点。在细胞病理学研究中，采用α-突触核蛋白免疫组织化学方法观察路易小体的形成过程或退变过程。在轴突运输受阻的异常细胞骨架中，α-突触核蛋白积聚形成路易小体，并伴随神经胶质和免疫反应变性。在临床病理研究中，将路易氏病理从I期分级到IV期，并根据路易氏病理或阿尔茨海默病的严重程度将尸检病例分为若干亚型。在额颞叶痴呆(FTD)中，匹克病(Pick‘s disease，PID)分为两种类型：泛素性痴呆和泛素性痴呆。

项目成果

Iseki E, Matsumura T, Marui W, et al.: "Familial frontotemporal dementia and parkinsonism with a novel N296H mutation in exon 10 of the gene and a widespread accumulation in the glial cells."Acta Neuropathol. 102. 285-292 (2001)

Iseki E、Matsumura T、Marui W 等人：“家族性额颞叶痴呆和帕金森病，其基因外显子 10 中出现新的 N296H 突变，并在神经胶质细胞中广泛积累。”Acta Neuropathol。

Marui W, Iseki E, Ueda K, Kosaka K: "Occurrence of human α-synuclein immunoreactive neurons with neurofibrillary tangle formation in the limbic areas of patients with Alzheimer's disease."J Neurol Sci. 174. 81-84 (2000)

Marui W、Iseki E、Ueda K、Kosaka K：“阿尔茨海默病患者边缘区域中人类 α-突触核蛋白免疫反应性神经元的发生与神经原纤维缠结的形成。”J Neurol Sci. 174. 81-84 (2000)

Togo T, Iseki E, Marui W, Akiyama H, Ueda K, Kosaka K: "Glial involvement in the degeneration process of Lewy body-bearing neurons and he degradation process of Lewy bodies in brains of dementia with Lewy bodies."J Neurol Sci. 184. 71-75 (2001)

Togo T、Iseki E、Marui W、Akiyama H、Ueda K、Kosaka K：“胶质细胞参与路易体神经元的变性过程，以及路易体痴呆患者大脑中路易体的降解过程。”J Neurol Sci

Iseki E, Takayama N, Marui W, Ueda K, Kosaka K: "Relationship in the formation process between neurofibrillary tangles and Lewy bodies in the hippocampus of dementia with Lewy bodies brains."J Neurol Sci. 195. 85-91 (2002)

Iseki E、Takayama N、Marui W、Ueda K、Kosaka K：“痴呆海马中神经原纤维缠结和路易体之间形成过程的关系与路易体大脑。”J Neurol Sci。

Iseki E, Tsunoda S, Suzuki K, et al.: "Regional quantitative analysis of NFT in brains of non-demented elderly persons : Comparisons with findings in brains of late-onset Alzheimer's disease and limbic NFT dementia"Neuropathology. 22. 34-39 (2002)

Iseki E、Tsunoda S、Suzuki K 等人：“非痴呆老年人大脑中 NFT 的区域定量分析：与晚发性阿尔茨海默病和边缘 NFT 痴呆大脑中的发现进行比较”神经病理学。