アクセス数 : ?
ダウンロード数 : ?
ID 115634
著者
Miyata, Hironori University of Occupational and Environmental Health
Yamaguchi, Yoshitaka Tokushima University
Imamura, Morikazu University of Miyazaki
Okazaki, Mariya Tokushima University
Pasiana, Agriani Dini Tokushima University
Atarashi, Ryuichiro University of Miyazaki
Watanabe, Hitomi Kyoto University
Kondoh, Gen Kyoto University
キーワード
prions
prion protein
protein misfolding
neurodegeneration
transgenic mice
資料タイプ
学術雑誌論文
抄録
Conformational conversion of the cellular prion protein, PrPC, into the abnormally folded isoform, PrPSc, is a key pathogenic event in prion diseases. However, the exact conversion mechanism remains largely unknown. Transgenic mice expressing PrP with a deletion of the central residues 91–106 were generated in the absence of endogenous PrPC, designated Tg(PrPΔ91–106)/Prnp0/0 mice and intracerebrally inoculated with various prions. Tg(PrPΔ91–106)/Prnp0/0 mice were resistant to RML, 22L and FK-1 prions, neither producing PrPScΔ91–106 or prions in the brain nor developing disease after inoculation. However, they remained marginally susceptible to bovine spongiform encephalopathy (BSE) prions, developing disease after elongated incubation times and accumulating PrPScΔ91–106 and prions in the brain after inoculation with BSE prions. Recombinant PrPΔ91-104 converted into PrPScΔ91–104 after incubation with BSE-PrPSc-prions but not with RML- and 22L–PrPSc-prions, in a protein misfolding cyclic amplification assay. However, digitonin and heparin stimulated the conversion of PrPΔ91–104 into PrPScΔ91–104 even after incubation with RML- and 22L-PrPSc-prions. These results suggest that residues 91–106 or 91–104 of PrPC are crucially involved in prion pathogenesis in a strain-dependent manner and may play a similar role to digitonin and heparin in the conversion of PrPC into PrPSc.
掲載誌名
International Journal of Molecular Sciences
ISSN
14220067
16616596
cat書誌ID
AA12038549
出版者
MDPI
21
19
開始ページ
7260
発行日
2020-10-01
権利情報
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所