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Calpain-dependent disruption of nucleo-cytoplasmic transport in ALS motor neurons
http://hdl.handle.net/2261/61310
http://hdl.handle.net/2261/6131036c7ef2f-5ef6-4c38-8e30-81998102b61b
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
srep39994.pdf (2.0 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-01-19 | |||||
| タイトル | ||||||
| タイトル | Calpain-dependent disruption of nucleo-cytoplasmic transport in ALS motor neurons | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Amyotrophic lateral sclerosis | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Molecular neuroscience | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_6501 | |||||
| タイプ | journal article | |||||
| 著者 |
Yamashita, Takenari
× Yamashita, Takenari× Aizawa, Hitoshi× Teramoto, Sayaka× Akamatsu, Megumi× Kwak, Shin |
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| 著者所属 | ||||||
| 著者所属 | Graduate School of Medicine, The University of Tokyo | |||||
| 著者所属 | ||||||
| 著者所属 | Department of Neurology, Tokyo Medical University | |||||
| 著者所属 | ||||||
| 著者所属 | Clinical Research Center for Medicine, International University of Health and Welfare | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Nuclear dysfunction in motor neurons has been hypothesized to be a principal cause of amyotrophic lateral sclerosis (ALS) pathogenesis. Here, we investigated the mechanism by which the nuclear pore complex (NPC) is disrupted in dying motor neurons in a mechanistic ALS mouse model (adenosine deaminase acting on RNA 2 (ADAR2) conditional knockout (AR2) mice) and in ALS patients. We showed that nucleoporins (Nups) that constituted the NPC were cleaved by activated calpain via a Ca2+-permeable AMPA receptor-mediated mechanism in dying motor neurons lacking ADAR2 expression in AR2 mice. In these neurons, nucleo-cytoplasmic transport was disrupted, and the level of the transcript elongation enzyme RNA polymerase II phosphorylated at Ser2 was significantly decreased. Analogous changes were observed in motor neurons lacking ADAR2 immunoreactivity in sporadic ALS patients. Therefore, calpain-dependent NPC disruption may participate in ALS pathogenesis, and inhibiting Ca2+-mediated cell death signals may be a therapeutic strategy for ALS. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | UTokyo Research掲載「核と細胞質間の分子輸送経路の破綻が筋萎縮性側索硬化症に関与」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/disruption-of-molecule-transport-pathway-between-nucleus-and-cytoplasm-involved-in-als.html | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | UTokyo Research "Disruption of molecule transport pathway between nucleus and cytoplasm involved in ALS" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/disruption-of-molecule-transport-pathway-between-nucleus-and-cytoplasm-involved-in-als.html | |||||
| 書誌情報 |
Scientific Reports Online Edition 巻 7, p. 39994, 発行日 2017-01-03 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2045-2322 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | info:doi/10.1038/srep39994 | |||||
| 権利 | ||||||
| 権利情報 | Copyright © 2017, Rights Managed by Nature Publishing Group | |||||
| 著者版フラグ | ||||||
| 値 | publisher | |||||
| 出版者 | ||||||
| 出版者 | Nature Publishing Group | |||||
| 関係URI | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/disruption-of-molecule-transport-pathway-between-nucleus-and-cytoplasm-involved-in-als.html | |||||
| 関係URI | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/disruption-of-molecule-transport-pathway-between-nucleus-and-cytoplasm-involved-in-als.html | |||||
| 関係URI | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://dx.doi.org/10.1038/srep39994 | |||||
