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Neuronal glutathione loss leads to neurodegeneration involving gasdermin activation
http://hdl.handle.net/10422/00013505
http://hdl.handle.net/10422/0001350582fa7b88-7aa5-4293-8379-61abeaa4034b
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s41598-023-27653-w (3.3 MB)
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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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s41598-023-27653-w_MOESM1_ESM (675.1 kB)
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s41598-023-27653-w_MOESM3_ESM (162.6 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2023-03-02 | |||||
タイトル | ||||||
タイトル | Neuronal glutathione loss leads to neurodegeneration involving gasdermin activation | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Cell death in the nervous system | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Diseases of the nervous system | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Neurological disorders | |||||
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 | |||||
著者 |
HASHIMOTO, Shoko
× HASHIMOTO, Shoko× MATSUBA, Yukio× TAKAHASHI, Mika× KAMANO , Naoko× WATAMURA, Naoto× SASAGURI, Hiroki× TAKADO, Yuhei× YOSHIHARA, Yoshihiro× SAITO, Takashi× SAIDO, Takaomi C |
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著者別名 |
橋本, 翔子
× 橋本, 翔子 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Accumulating evidence suggests that glutathione loss is closely associated with the progression of neurodegenerative disorders. Here, we found that the neuronal conditional-knockout (KO) of glutamyl-cysteine-ligase catalytic-subunit (GCLC), a rate-limiting enzyme for glutathione synthesis, induced brain atrophy accompanied by neuronal loss and neuroinflammation. GCLC-KO mice showed activation of C1q, which triggers engulfment of neurons by microglia, and disease-associated-microglia (DAM), suggesting that activation of microglia is linked to the neuronal loss. Furthermore, gasdermins, which regulate inflammatory form of cell death, were upregulated in the brains of GCLC-KO mice, suggesting the contribution of pyroptosis to neuronal cell death in these animals. In particular, GSDME-deficiency significantly attenuated the hippocampal atrophy and changed levels of DAM markers in GCLC-KO mice. Finally, we found that the expression of GCLC was decreased around amyloid plaques in AppNL-G-F AD model mice. AppNL-G-F mouse also exhibited inflammatory events similar to GCLC-KO mouse. We propose a mechanism by which a vicious cycle of oxidative stress and neuroinflammation enhances neurodegenerative processes. Furthermore, GCLC-KO mouse will serve as a useful tool to investigate the molecular mechanisms underlying neurodegeneration and in the development of new treatment strategies to address neurodegenerative diseases. | |||||
書誌情報 |
en : Scientific Reports 巻 13, 号 1, 発行日 2023-01-20 |
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出版者 | ||||||
出版者 | Springer Nature | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2045-2322 | |||||
PMID | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 36670138 | |||||
PMCID | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9859798/ | |||||
関連名称 | PMC9859798 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1038/s41598-023-27653-w | |||||
関連名称 | 10.1038/s41598-023-27653-w | |||||
権利 | ||||||
権利情報 | © The Author(s) 2023 | |||||
フォーマット | ||||||
内容記述タイプ | Other | |||||
内容記述 | application/pdf | |||||
フォーマット | ||||||
内容記述タイプ | Other | |||||
内容記述 | application/xlsx | |||||
資源タイプ | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal Article |