Possible role of glial cells in the progression of Alzheimer's disease pathology

神经胶质细胞在阿尔茨海默氏病病理进展中的可能作用

• 批准号: 18500279
• 负责人: MORI Takashi
• 金额: $ 2.75万
• 依托单位: Saitama Medical University
• 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 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18500279/
• 关键词: 神経科学; 脳神経変性疾患; 神経病理学; 細胞・組織; 獣医学; 脳神経疾患; 病理学

Here, we aimed to examine the possible role of astrocyte-derived S100B in the progression of Alzheimer's disease pathology. First, using Alzheimer's disease model mice, we showed that Alzheimer's disease-like pathology was significantly ameliorated by the treatment of arundic acid [(R)-(-)-2-propyloctanoic acid], which is known to negatively regulate astrocyte synthesis of S100B. Subsequently, to dissect the relationship between S100B and Alzheimer's disease-like pathology, we took a genetic approach by crossing transgenic mice expressing human S100B with Alzheimer's disease model mice. We demonstrated evidence that (over)-expression of S100B acts to accelerate Alzheimer's disease-like pathology. Taken together, these data suggest that inhibiting astrocytic activation by blocking S100B biosynthesis may be a promising therapeutic strategy to delay Alzheimer's disease progression.

在这里，我们的目的是研究星形胶质细胞衍生的S100 B在阿尔茨海默病病理学进展中的可能作用。首先，使用阿尔茨海默病模型小鼠，我们表明阿尔茨海默病样病理学通过Arundic酸[（R）-（-）-2-propyloctanoic acid]的治疗显著改善，已知Arundic酸负调节星形胶质细胞S100 B的合成。随后，为了剖析S100 B和阿尔茨海默病样病理学之间的关系，我们采用遗传方法，将表达人S100 B的转基因小鼠与阿尔茨海默病模型小鼠杂交。我们证明了S100 B（过）表达加速阿尔茨海默病样病理的证据。总之，这些数据表明，通过阻断S100 B生物合成来抑制星形胶质细胞活化可能是一种有前途的延缓阿尔茨海默病进展的治疗策略。

项目成果

Huntington Potter. Caffeine reverses cognitive impairment and decreases brain amyloid-βlevels in aged Alzheimer's disease mice.

亨廷顿·波特 (Huntington Potter) 指出，咖啡因可逆转老年阿尔茨海默病小鼠的认知障碍并降低大脑淀粉样蛋白水平。

• 发表时间: 2009
• 期刊: J Alzheimer's Dis 17(3)
• 作者: Gary W. Arendash;Takashi Mori;Chuanhai Cao;Malgorzata B. Mamcarz;Melissa J. Runfeldt;Alexander Dickson;Kavon Rezai-Zadeh;Jun Tan;Bruce A. Citron;Xiaoyang Lin;Valentina Echeverria
• 通讯作者: Valentina Echeverria

A new therapeutic agent for Alzheimer disease: Arundic acid (ONO-2506) attenuates cerebral amyloidosis and gliosis in Alzheimer transgenic mice.

阿尔茨海默病的新治疗剂：Arundic Acid (ONO-2506) 可减轻阿尔茨海默病转基因小鼠的脑淀粉样变性和神经胶质增生。

• 发表时间: 2007
• 作者: Takashi Mori;Terrence Town;Jun Tan;Nobumichi Yada;Junki Yamamoto;Masamitsu Hoshikawa;Rika Shinagawa;Yoshihisa Kamanaka;Naoki Koyama;Takao Asano.
• 通讯作者: Takao Asano.

Transcutaneous β-amyloid peptide immunization reduces cerebral β-amyloid deposits without T cell infiltration and microhemorrhage.

经皮 β-淀粉样肽免疫减少大脑 β-淀粉样蛋白沉积，且无 T 细胞浸润和微出血。

• 发表时间: 2007
• 期刊: Proc Natl Acad Sci U.S.A. 104(7)
• 作者: William V. Nikolic;Yun Bai;Demian F. Obregon;Huayan Hou;Takashi Mori;Jin Zeng;Jared Ehrhart;R. Douglas Shytle;Brian Giunta;Dave Morgan;Terrence Town;Jun Tan.
• 通讯作者: Jun Tan.

Douglas Shytle, Brian Giunta, Dave Morgan, Terrence Town, Jun Tan. Transcutaneous β-amyloid peptide immunization reduces cerebral β-amyloid deposits without T cell infiltration and microhemorrhage

Douglas Shytle、Brian Giunta、Dave Morgan、Terrence Town、Jun Tan。

• 发表时间: 2007
• 期刊: Proc Natl Acad Sci U. S. A. 104 (7)
• 作者: William V. Nikolic;Yun Bai;Demian F. Obregon;Huayan Hou;Takashi Mori;Jin Zeng;Jared Ehrhart;R.
• 通讯作者: R.

ヒトS100B蛋白の過剰発現はアルツハイマー様病態(脳アミロイド症・グリオーシス)を増悪させる.

人类 S100B 蛋白的过度表达会加剧阿尔茨海默样病变（大脑淀粉样变性和神经胶质增生）。

• 发表时间: 2009
• 作者: 小山直基;堀越(櫻庭)優子;森隆
• 通讯作者: 森隆