Deciphering changes in intracellular signals during axon degeneration

解读轴突变性期间细胞内信号的变化

• 批准号: 23650184
• 负责人: FUJIWARA Takeshi
• 金额: $ 2.41万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23650184/
• 关键词: 分子神経病理学; 軸索変性; 神経; 軸索; 逆行性物質輸送; 微小管; p53; アルツハイマー病; 神経変性疾患; ダイニン・ダイナクチン複合体; p150Glued; DIC

In this study, our specific aim is to decipher mechanisms and factors that regulate the process of axon degeneration, a hallmark phenotype observed in various neurological disorders including Alzheimer’s disease. We developed aglutamate excitotoxicity-induced axon degeneration system in primary neuronal culturesand found that p150Glued and dynein intermediate chain (DIC), both of which are major components of the retrograde transport dynein-dynactin complex, microtubule stabilization, and inhibition of p53 transactivation regulate the process of axondegeneration including axon degeneration. As glutamate excitotoxicity is implicated in various neurological deficits, our findings identify retrograde transport proteins,microtubule dynamics, and tumor suppressor protein p53 as novel intracellular signalingmodulators of axon degeneration observed in neurological disorders.

在这项研究中，我们的具体目标是破译调节轴突变性过程的机制和因素，轴突变性是在包括阿尔茨海默病在内的各种神经系统疾病中观察到的标志性表型。我们在原代培养的神经元中建立了谷氨酸兴奋性毒性诱导的轴突变性系统，发现p150 Glued和动力蛋白中间链（DIC），两者都是逆行运输动力蛋白-动力蛋白复合物的主要成分，微管稳定和抑制p53反式激活调节轴突变性过程，包括轴突变性。由于谷氨酸兴奋性毒性与各种神经功能缺损有关，我们的研究结果确定了逆行转运蛋白、微管动力学和肿瘤抑制蛋白p53作为神经系统疾病中观察到的轴突变性的新型细胞内信号调节剂。

项目成果

Axonal transport proteins implicated in the pathology of Alzheimer’s disease.

轴突转运蛋白与阿尔茨海默病的病理学有关。

• 发表时间: 2013
• 作者: Takeshi Fujiwara;Koji Morimoto;Akiyoshi Kakita;and Hitoshi Takahashi;Takeshi Fujiwara
• 通讯作者: Takeshi Fujiwara

Dynein and dynactin components modulate neurodegeneration induced by excitotoxicity

• DOI: 10.1111/j.1471-4159.2012.07746.x
• 发表时间: 2012-07-01
• 期刊: JOURNAL OF NEUROCHEMISTRY
• 影响因子: 4.7
• 作者: Fujiwara, Takeshi;Morimoto, Koji;Takahashi, Hitoshi
• 通讯作者: Takahashi, Hitoshi

Axonal transport proteins implicated in the pathology of Alzheimer's disease

轴突转运蛋白与阿尔茨海默病的病理学有关

• 发表时间: 2013
• 作者: Takeshi Fujiwara;Koji Morimoto;Akiyoshi Kakita;and Hitoshi Takahashi
• 通讯作者: and Hitoshi Takahashi

Cooperative effect of p150Glued and microtubule stabilization to suppress excitotoxicity-induced axon degeneration

• DOI: 10.1016/j.bbrc.2012.06.071
• 发表时间: 2012-07-20
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Fujiwara, Takeshi;Morimoto, Koji
• 通讯作者: Morimoto, Koji

Cell surface biotinylation by azaelectrocyclization: easy-handling and versatile approach for living cell labeling.

• DOI: 10.1016/j.bmc.2011.12.043
• 发表时间: 2012-03
• 期刊: Bioorganic & medicinal chemistry
• 影响因子: 3.5
• 作者: Katsunori Tanaka;Satomi Yokoi;Koji Morimoto;Takayuki Iwata;Y. Nakamoto;K. Nakayama;K. Kôyama;Takeshi Fujiwara;K. Fukase