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Tau binding protein CAPON induces tau aggregation and neurodegeneration
https://repo.qst.go.jp/records/75972
https://repo.qst.go.jp/records/75972e0bb2e5d-f492-4ec5-8b5a-675514a5e2fe
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-06-04 | |||||
| タイトル | ||||||
| タイトル | Tau binding protein CAPON induces tau aggregation and neurodegeneration | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Hashimoto, Shoko
× Hashimoto, Shoko× Matsuba, Yukio× Kamano, Naoko× MIhira, Naomi× Sahara, Naruhiko× Takano, Jiro× Shin-ichi, Muramatsu× C. Saido, Takaomi× Saito, Takashi× Sahara, Naruhiko |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | To understand the molecular processes that link Aβ amyloidosis, tauopathy and neurodegeneration, we screened for tau-interacting proteins by immunoprecipitation/LC-MS. We identified the carboxy-terminal PDZ ligand of nNOS (CAPON) as a novel tau-binding protein. CAPON is an adaptor protein of neuronal nitric oxide synthase (nNOS), and activated by the N-methyl-D-aspartate receptor. We observed accumulation of CAPON in the hippocampal pyramidal cell layer in the AppNL-G-F -knock-in (KI) brain. To investigate the effect of CAPON accumulation on Alzheimer’s disease (AD) pathogenesis, CAPON was overexpressed in the brain of AppNL-G-F mice crossbred with MAPT (human tau)-KI mice. This produced significant hippocampal atrophy and caspase3-dependent neuronal cell death in the CAPON-expressing hippocampus, suggesting that CAPON accumulation increases neurodegeneration. CAPON expression also induced significantly higher levels of phosphorylated, oligomerized and insoluble tau. In contrast, CAPON deficiency ameliorated the AD-related pathological phenotypes in tauopathy model. These findings suggest that CAPON could be a druggable AD target. | |||||
| 書誌情報 |
Nature Communications 巻 10, 号 1, p. 2394, 発行日 2019-06 |
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| 出版者 | ||||||
| 出版者 | Nature.com | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2041-1723 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 31160584 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1038/s41467-019-10278-x | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.nature.com/articles/s41467-019-10278-x | |||||
