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ID 115634
Author
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
Keywords
prions
prion protein
protein misfolding
neurodegeneration
transgenic mice
Content Type
Journal Article
Description
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.
Journal Title
International Journal of Molecular Sciences
ISSN
14220067
16616596
NCID
AA12038549
Publisher
MDPI
Volume
21
Issue
19
Start Page
7260
Published Date
2020-10-01
Rights
© 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/).
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DOI (Published Version)
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language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences