FK506 reduces abnormal prion protein through the activation of autolysosomal degradation and prolongs survival in prion-infected mice

Prion diseases are fatal neurodegenerative disorders and no effective treatment has been established to date. In this study, we evaluated the effect of FK506 (tacrolimus), a macrolide that is known to be a mild immunosuppressant, on prion infection, using cell culture and animal models. We found that FK506 markedly reduced the abnormal form of prion protein (PRNPSc) in the cell cultures (N2a58 and MG20) infected with Fukuoka-1 prion. The levels of autophagy-related molecules such as LC3-II, ATG12?ATG5 and ATG7 were significantly increased in the FK506-treated cells, and resulted in the increased formation of autolysosomes. Upregulation of the autophagy-related molecules was also seen in the brains of FK506-treated mice and the accumulation of PRNPSc was delayed. The survival periods in mice inoculated with Fukuoka-1 were significantly increased when FK506 was administered from day 20 post-inoculation. These findings provide evidence that FK506 could constitute a novel antiprion drug, capable of enhancing the degradation of PRNPSc in addition to attenuation of microgliosis and neuroprotection.;開始ページ : 1386;終了ページ : 1394;元資料の権利情報 : © 2013 Landes Bioscience;元資料の権利情報 : This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

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書名 FK506 reduces abnormal prion protein through the activation of autolysosomal degradation and prolongs survival in prion-infected mice
著作者等 中垣 岳大
書名別名 FK506はオートファジーを活性化することで異常型プリオンタンパクの分解を促進し、プリオン感染マウスの生存期間を延長する
出版元 Landes Bioscience
刊行年月 c2005-
ページ数 v.
大きさ 28 cm
ISSN 15548627
NCID AA12157457
※クリックでCiNii Booksを表示
言語 英語
出版国 アメリカ合衆国
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