Regulation of autophagy by Na+/H+exchangers

Na /H 交换剂对自噬的调节

• 批准号: 22700407
• 负责人: TOGASHI Kazuya
• 金额: $ 2.5万
• 依托单位: National Center of Neurology and Psychiatry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22700407/
• 关键词: Na+/H+交換輸送体; オートファジー; 神経変性疾患

Autophagy is an intracellular degradation process that clears long-lived proteins and organelles from the cytoplasm, and then maintains normal cellular functions. Thus failure of autophagy in neurons can result in the accumulation of aggregate-prone proteins and neurodegeneration. However, the regulation mechanism of autophagy in brain is less known. In the present study, I found that an NHE blocker inhibited autophagy and that the over expression of plasma membrane type NHEs significantly reduced the formation of poly glutamine aggregation in a cell-line. Moreover, NHE5KO/Htt-Tg mice were generated by crossing with NHE5 knockout mouse and a Huntington's disease model mouse in which a large number of aggregations were observed in the cerebellar granule cells.

自噬是一种细胞内降解过程，它清除细胞质中的长寿命蛋白质和细胞器，然后维持正常的细胞功能。因此，神经元自噬的失败可导致易聚集蛋白的积累和神经变性。然而，大脑自噬的调控机制尚不清楚。在本研究中，我发现一种NHE阻断剂可以抑制自噬，质膜型NHE的过表达可以显著减少细胞系中聚谷氨酰胺聚集物的形成。通过与NHE5基因敲除小鼠和亨廷顿病模型小鼠杂交产生NHE5KO/Htt-Tg小鼠，在小脑颗粒细胞中观察到大量聚集。

项目成果

Regulation of Autophagy by Na+/H+Exchanger(s)

Na /H 交换体对自噬的调节

• 发表时间: 2011
• 作者: 冨樫和也;荒木敏之
• 通讯作者: 荒木敏之

Na+/H+交換輸送体によるオートファジーの調節

Na+/H+ 交换转运蛋白对自噬的调节

• 发表时间: 2011
• 作者: 冨樫和也;荒木敏之;冨樫和也・荒木敏之
• 通讯作者: 冨樫和也・荒木敏之

Na+/H+交換輸送体の強制発現によるポリグルタミン凝集の抑制

通过 Na+/H+ 交换转运蛋白的强制表达抑制多聚谷氨酰胺聚集

• 发表时间: 2010
• 作者: 冨樫和也;荒木敏之
• 通讯作者: 荒木敏之