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Atp13a2欠損ゼブラフィッシュにおけるドーパミン神経変性と細胞内輸送障害
http://hdl.handle.net/10191/0002000292
http://hdl.handle.net/10191/0002000292f6469641-698d-4aae-9a20-27191043440d
名前 / ファイル | ライセンス | アクション |
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本文 (1.95MB)
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要旨 (546KB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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公開日 | 2022-04-04 | |||||||||
タイトル | ||||||||||
言語 | en | |||||||||
タイトル | Degeneration of dopaminergic neurons and impaired intracellular trafficking in Atp13a2 deficient zebrafish | |||||||||
タイトル | ||||||||||
言語 | ja | |||||||||
タイトル | Atp13a2欠損ゼブラフィッシュにおけるドーパミン神経変性と細胞内輸送障害 | |||||||||
言語 | ||||||||||
言語 | eng | |||||||||
キーワード | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | Parkinson's disease | |||||||||
キーワード | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | ATP13A2 | |||||||||
キーワード | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | Zebrafish | |||||||||
キーワード | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | Trafficking impairment | |||||||||
資源タイプ | ||||||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||||||
タイプ | doctoral thesis | |||||||||
アクセス権 | ||||||||||
アクセス権 | open access | |||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
著者 |
入月, 浩美
× 入月, 浩美
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抄録 | ||||||||||
内容記述タイプ | Abstract | |||||||||
内容記述 | ATP13A2 is the autosomal recessive causative gene for juvenile-onset Parkinson's disease (PARK9, Parkinson's disease 9), also known as Kufor-Rakeb syndrome. The disease is characterized by levodopa-responsive Parkinsonism, supranuclear gaze palsy, spasticity, and dementia. Previously, we have reported that Atp13a2 deficient medaka fish showed dopaminergic neurodegeneration and lysosomal dysfunction, indicating that lysosome-autophagy impairment might be one of the key pathogeneses of Parkinson's disease. Here, we established Atp13a2 deficient zebrafish using CRISPR/Cas9 gene editing. We found that the number of TH + neurons in the posterior tuberculum and the locus coeruleus significantly reduced (dopaminergic neurons, 64% at 4 months and 37% at 12 months, p < 0.001 and p < 0.05, respectively; norepinephrine neurons, 52% at 4 months and 40% at 12 months, p < 0.001 and p < 0.05, respectively) in Atp13a2 deficient zebrafish, proving the degeneration of dopaminergic neurons. In addition, we found the reduction (60%, p < 0.05) of cathepsin D protein expression in Atp13a2 deficient zebrafish using immunoblot. Transmission electron microscopy analysis using middle diencephalon samples from Atp13a2 deficient zebrafish showed lysosome-like bodies with vesicle accumulation and fingerprint-like structures, suggesting lysosomal dysfunction. Furthermore, a significant reduction (p < 0.001) in protein expression annotated with vesicle fusion with Golgi apparatus in Atp13a2 deficient zebrafish by liquid-chromatography tandem mass spectrometry suggested intracellular trafficking impairment. Therefore, we concluded that Atp13a2 deficient zebrafish exhibited degeneration of dopaminergic neurons, lysosomal dysfunction and the possibility of intracellular trafficking impairment, which would be the key pathogenic mechanism underlying Parkinson's disease. | |||||||||
言語 | en | |||||||||
内容記述 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | IBRO Reports. 2020, 9, 1-8. | |||||||||
言語 | en | |||||||||
DOI | ||||||||||
識別子タイプ | DOI | |||||||||
関連識別子 | https://doi.org/10.1016/j.ibror.2020.05.002 | |||||||||
権利 | ||||||||||
言語 | en | |||||||||
権利情報 | 【○!C】 2020 The Author(s). Published by Elsevier Ltd on behalf of International Brain Research Organization. | |||||||||
権利 | ||||||||||
言語 | en | |||||||||
権利情報Resource | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||||||
権利情報 | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International | |||||||||
学位名 | ||||||||||
言語 | ja | |||||||||
学位名 | 博士(医学) | |||||||||
学位授与機関 | ||||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||
学位授与機関識別子 | 13101 | |||||||||
言語 | ja | |||||||||
学位授与機関名 | 新潟大学 | |||||||||
言語 | en | |||||||||
学位授与機関名 | Niigata University | |||||||||
学位授与年月日 | ||||||||||
学位授与年月日 | 2021-03-23 | |||||||||
学位授与番号 | ||||||||||
学位授与番号 | 甲第4833号 | |||||||||
学位記番号 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | 新大院博(医)第987号 | |||||||||
言語 | ja |