Molecular mechanism underlying promotion of neuronal regeneration

促进神经元再生的分子机制

• 批准号: 17300113
• 负责人: KIYAMA Hiroshi
• 金额: $ 9.6万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17300113/
• 关键词: ATF3; cJun; STAT3; Neuronal regeneration; hypoglossal nerve; Akt

This study was carried out to investigate "Molecular mechanism underlying promotion of neuronal regeneration". Two major topics were investigated : (1) Identification of transcription factors and epigenetic factors, which are associated with neuronal regeneration, (2) Identification of protein modification, which promotes neuronal regeneration. We have revealed that transcription factors such as ATF3, cJun and STAT3 were crucial to promote nerve regeneration, and further tried to understand the interaction of those transcription factors using the promoter for one of nerve regeneration associated molecules, damage induced neuronal endopeptidase DINE. This analysis demonstrated that those transcription factors seemed not to bind the promoter region directly, and instead suggested the existence of a sort of platform molecule for the assembly of those transcription factors. The transcriptional control identified in this study may be specific to nerve regeneration and would provide a novel … More transcription mechanism for the promotion of nerve regeneration. We have also attempted to identify protein modifications such as phosphorylation, methylation, and acetylation for the promotion of nerve regeneration. To identify the modified molecules in response to nerve injury, we used 2-DG electrophoresis and blotted with antibodies, which recognized a certain kinase specific phosphorylation site for instance. The candidate spots, which showed up-regulation of the modification were further analyzed by TOFMAS. We have identified pheripherin as a phosphorylated molecule by Akt in response to nerve injury. Although the functional significance of the phosphorylation is not clear, the method established in this experiment could be a good tool for the identification of the proteins, which are modified by phosphorylation, methylation, or acetylation. The results obtained in the present project provide us with a novel transcription mechanism underlying the nerve regeneration, and also provide useful tool for the identification of molecular modification by phosphorylation, methylation, and acetylation. Less

本研究旨在探讨“促进神经元再生的分子机制”。主要研究了两个主题：（1）与神经元再生相关的转录因子和表观遗传因子的鉴定，（2）促进神经元再生的蛋白质修饰的鉴定。我们已经发现，转录因子如ATF 3，cJun和STAT 3是至关重要的，以促进神经再生，并进一步试图了解这些转录因子的相互作用，使用神经再生相关分子之一，损伤诱导神经元内肽酶DINE的启动子。这一分析表明，这些转录因子似乎不直接结合启动子区，而是暗示存在一种平台分子，用于组装这些转录因子。这项研究中确定的转录控制可能是特异性的神经再生，并将提供一个新的 ...更多信息 促进神经再生的转录机制。我们还试图确定蛋白质修饰，如磷酸化，甲基化和乙酰化，以促进神经再生。为了鉴定对神经损伤作出反应的修饰分子，我们使用2-DG电泳和用抗体印迹，其识别例如某个激酶特异性磷酸化位点。通过TOFMAS进一步分析显示修饰上调的候选点。我们已经确定了磷酸化的分子Akt在神经损伤的反应。虽然磷酸化的功能意义尚不清楚，但本实验建立的方法可以很好地用于鉴定通过磷酸化、甲基化或乙酰化修饰的蛋白质。本项目的研究结果为神经再生提供了一种新的转录机制，也为鉴定磷酸化、甲基化和乙酰化等分子修饰提供了有用的工具。少

项目成果

Expression of Reg/PAP family members during motor nerve regeneration in rat

• DOI: 10.1016/j.bbrc.2005.04.105
• 发表时间: 2005-06-24
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Namikawa, K;Fukushima, M;Kiyama, H
• 通讯作者: Kiyama, H

A newly modified SCG10 promoter and Cre/IoxP-mediated gene amplification system achieve highly specific neuronal expression in animal brains

新修饰的SCG10启动子和Cre/IoxP介导的基因扩增系统在动物大脑中实现高度特异性的神经元表达

• 发表时间: 2006
• 期刊: Gene Therapy 13(16)
• 作者: Namikawa K;Murakami K;Okamoto T;Okado H;Kiyama H
• 通讯作者: Kiyama H

GTP hydrolysis by the Rho family GTPase TC10 promotes exocytic vesicle fusion

• DOI: 10.1016/j.devcel.2006.07.008
• 发表时间: 2006-09-01
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: Kawase, Kazuho;Nakamura, Takeshi;Matsuda, Michiyuki
• 通讯作者: Matsuda, Michiyuki

Localization and ontogeny of damage-induced neuronal endopeptidase (DINE) mRNA-expressing neurons in the rat nervous system

大鼠神经系统中损伤诱导的神经元内肽酶 (DINE) mRNA 表达神经元的定位和个体发育

• 发表时间: 2006
• 期刊: Neuroscience 141(1)
• 作者: Nagata K;Kiryu-Seo S;Kiyama H
• 通讯作者: Kiyama H

Related Articles, Links Identification and functional characterization of mouse TPO1 as a myelin membrane protein.

相关文章、链接 小鼠 TPO1 作为髓磷脂膜蛋白的鉴定和功能表征。

• 发表时间: 2006
• 期刊: Brain Res. 1070
• 作者: Fukazawa N;Ayukawa K;Nishikawa K;Ohashi H;Ichihara N;Hikawa Y;Abe T;Kudo Y;Kiyama H;Wada K;Aoki S.
• 通讯作者: Aoki S.