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Effect of Trehalose on the Properties of Mutant γPKC, Which Causes Spinocerebellar Ataxia Type 14, in Neuronal Cell Lines and Cultured Purkinje Cells

https://hiroshima.repo.nii.ac.jp/records/2008924
https://hiroshima.repo.nii.ac.jp/records/2008924
e943bef7-9747-4e3c-996b-dd6dba3e1d10
名前 / ファイル ライセンス アクション
JBC_285_33252.pdf JBC_285_33252.pdf (6.1 MB)
Item type デフォルトアイテムタイプ_(フル)(1)
公開日 2023-03-18
タイトル
タイトル Effect of Trehalose on the Properties of Mutant γPKC, Which Causes Spinocerebellar Ataxia Type 14, in Neuronal Cell Lines and Cultured Purkinje Cells
言語 en
作成者 Seki, Takahiro

× Seki, Takahiro

en Seki, Takahiro

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Abe-Seki, Nana

× Abe-Seki, Nana

en Abe-Seki, Nana

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Kikawada, Takahiro

× Kikawada, Takahiro

en Kikawada, Takahiro

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Takahashi, Hideyuki

× Takahashi, Hideyuki

en Takahashi, Hideyuki

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Yamamoto, Kazuhiro

× Yamamoto, Kazuhiro

en Yamamoto, Kazuhiro

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Adachi, Naoko

× Adachi, Naoko

en Adachi, Naoko

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Tanaka, Shigeru

× Tanaka, Shigeru

en Tanaka, Shigeru

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Hide, Izumi

× Hide, Izumi

en Hide, Izumi

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Saito, Naoaki

× Saito, Naoaki

en Saito, Naoaki

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Sakai, Norio

× Sakai, Norio

en Sakai, Norio

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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
権利情報
権利情報 Copyright (c) 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
主題
主題Scheme NDC
主題 490
内容記述
内容記述 Several missense mutations in the protein kinase C gamma (gamma PKC) gene have been found to cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease. We previously demonstrated that the mutant gamma PKC found in SCA14 is susceptible to aggregation, which induces apoptotic cell death. The disaccharide trehalose has been reported to inhibit aggregate formation and to alleviate symptoms in cellular and animal models of Huntington disease, Alzheimer disease, and prion disease. Here, we show that trehalose can be incorporated into SH-SY5Y cells and reduces the aggregation of mutant gamma PKC-GFP, thereby inhibiting apoptotic cell death in SH-SY5Y cells and primary cultured Purkinje cells (PCs). Trehalose acts by directly stabilizing the conformation of mutant gamma PKC without affecting protein turnover. Trehalose was also found to alleviate the improper development of dendrites in PCs expressing mutant gamma PKC-GFP without aggregates but not in PCs with aggregates. In PCs without aggregates, trehalose improves the mobility and translocation of mutant gamma PKC-GFP, probably by inhibiting oligomerization and thereby alleviating the improper development of dendrites. These results suggest that trehalose counteracts various cellular dysfunctions that are triggered by mutant gamma PKC in both neuronal cell lines and primary cultured PCs by inhibiting oligomerization and aggregation of mutant gamma PKC.
言語 en
出版者
出版者 American Society for Biochemistry and Molecular Biology Inc
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
出版タイプ
出版タイプ AO
出版タイプResource http://purl.org/coar/version/c_b1a7d7d4d402bcce
関連情報
識別子タイプ DOI
関連識別子 10.1074/jbc.M110.146704
関連情報
識別子タイプ DOI
関連識別子 http://dx.doi.org/10.1074/jbc.M110.146704
収録物識別子
収録物識別子タイプ ISSN
収録物識別子 0021-9258
収録物識別子
収録物識別子タイプ NCID
収録物識別子 AA00251083
開始ページ
開始ページ 33252
書誌情報 The Journal of Biological Chemistry
The Journal of Biological Chemistry

巻 285, 号 43, p. 33252-33264, 発行日 2010-08-12
旧ID 30787
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