The elucidation of onset mechanism of Alzheimer's disease.

阐明阿尔茨海默病的发病机制。

• 批准号: 18590355
• 负责人: ISHIGAMI Akihito
• 金额: $ 2.5万
• 依托单位: Tokyo Metropolitan Institute of Gerontology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590355/
• 关键词: Alzheimer's disease; neurodegenerative disorder; citrullinated protein; neuron; astrocyte; apoptosis; calcium; arginine

Citrullinated proteins are the products of a post-translational process in which arginine residues undergo modification into citrulline residues when catalyzed by peptidylarginine deiminases (PADs) in a calcium ion-dependent manner Enzymatic citrullination abolishes positive charges of native protein molecules, inevitably causing significant alterations in their structure and functions. In mammalian tissues, PADs are found as five different isoforms (i.e, types 1-4, 6). PAD2 expressed mainly in the rat cerebrum became activated early in the neurodegenerative process. To elucidate the involvement of the citrullination in neuronal degeneration, we examined whether citrullinated proteins are produced in Alzheimer's disease (AD), Parkinson's disease, and Huntington chorea.1. Histochemical analysis revealed that citrullinated proteins were detected all over the hippocampus. However, no citrullinated proteins were detected in the normal hippocampus. PAD2 immunoreactivity was also detected all over the hippocampus both in the AD and the normal brain. Double immunofluorescence staining revealed that citrullinated protein-and PAD2-positive cells were well coincidenced with GFAP-positive cells, but not all GFAP-positive cells were PAD2-positive cells. As GFAP is a astrocyte-specific marker protein, PAD2 is distributed mainly in astrocytes.2. Citrullinated proteins with various molecular weight were detected in AD hippocampus by Western blot analysis, but not in normal brain. Two of the citrullinated proteins were identified as a vimentin and a glial fibrillary acidic protein (GFAP).Thus, abnormal accumulation of citrullinated proteins and abnormal activation of PAD2 is occurring in AD hippocampus. These results strongly suggested that PAD has an important role in the onset and progression of AD and citrullinated proteins may became a possible useful marker for human neurodegenerative disease.

瓜氨酸化蛋白质是翻译后过程的产物，其中精氨酸残基在肽基精氨酸脱亚胺酶 (PAD) 的催化下以钙离子依赖性方式修饰为瓜氨酸残基。酶促瓜氨酸化消除了天然蛋白质分子的正电荷，不可避免地导致其结构和功能发生显着改变。在哺乳动物组织中，PAD 有五种不同的亚型（即 1-4、6 型）。 PAD2 主要在大鼠大脑中表达，在神经退行性过程的早期被激活。为了阐明瓜氨酸化在神经元变性中的作用，我们检查了阿尔茨海默病（AD）、帕金森病和亨廷顿舞蹈病中是否产生瓜氨酸化蛋白。1。组织化学分析表明，在整个海马体中都检测到了瓜氨酸蛋白。然而，在正常海马中没有检测到瓜氨酸蛋白。在 AD 和正常大脑的整个海马体中也检测到了 PAD2 免疫反应性。双重免疫荧光染色显示瓜氨酸蛋白和 PAD2 阳性细胞与 GFAP 阳性细胞高度一致，但并非所有 GFAP 阳性细胞都是 PAD2 阳性细胞。由于GFAP是星形胶质细胞特有的标记蛋白，PAD2主要分布于星形胶质细胞中。2． Western blot分析在AD海马中检测到了不同分子量的瓜氨酸蛋白，但在正常大脑中未检测到。其中两种瓜氨酸蛋白被鉴定为波形蛋白和神经胶质纤维酸性蛋白(GFAP)。因此，AD海马中发生瓜氨酸蛋白的异常积累和PAD2的异常激活。这些结果强烈表明，PAD 在 AD 的发生和进展中具有重要作用，瓜氨酸蛋白可能成为人类神经退行性疾病的可能有用标记。

项目成果

ビタミンC不足は慢性閉塞性肺疾患の発症リスクを高める.

维生素 C 缺乏会增加患慢性阻塞性肺病的风险。

• 发表时间: 2008
• 期刊: ビタミン 82
• 作者: Park;JK.;Et. al.;石神 昭人
• 通讯作者: 石神 昭人

Accelerated tubular cell senescence in SMP30 knockout mice.

• DOI: 10.14670/hh-21.1151
• 发表时间: 2006-11
• 期刊: Histology and histopathology
• 影响因子: 2
• 作者: W. Yumura;T. Imasawa;S. Suganuma;A. Ishigami;S. Handa;S. Kubo;K. Joh;N. Maruyama

Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy

• DOI: 10.1073/pnas.0511225103
• 发表时间: 2006-04-11
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Kondo, Y;Inai, Y;Ishigami, A
• 通讯作者: Ishigami, A

A selective NFkappaB inhibitor, DHMEQ, reduced atherosclerosis in ApoE-deficient mice.

• 发表时间: 2006
• 期刊: Journal of atherosclerosis and thrombosis
• 影响因子: 4.4
• 作者: T. Chiba;Y. Kondo;Shohei Shinozaki;E. Kaneko;A. Ishigami;N. Maruyama;K. Umezawa;K. Shimokado

肺の老化メカニズム.

肺衰老的机制。

• 发表时间: 2007
• 期刊: THE LUNG perspectives 15
• 作者: 佐藤 匡;他
• 通讯作者: 他