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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-39974

Sigurdson, C J; Nilsson, K P R; Hornemann, S; Manco, G; Fernández-Borges, N; Schwarz, P; Castilla, J; Wüthrich, K; Aguzzi, A (2010). A molecular switch controls interspecies prion disease transmission in mice. Journal of Clinical Investigation, 120(7):2590-2599.

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Abstract

Transmissible spongiform encephalopathies are lethal neurodegenerative disorders that present with aggregated forms of the cellular prion protein (PrPC), which are known as PrPSc. Prions from different species vary considerably in their transmissibility to xenogeneic hosts. The variable transmission barriers depend on sequence differences between incoming PrPSc and host PrPC and additionally, on strain-dependent conformational properties of PrPSc. The beta2-alpha2 loop region within PrPC varies substantially between species, with its structure being influenced by the residue types in the 2 amino acid sequence positions 170 (most commonly S or N) and 174 (N or T). In this study, we inoculated prions from 5 different species into transgenic mice expressing either disordered-loop or rigid-loop PrPC variants. Similar beta2-alpha2 loop structures correlated with efficient transmission, whereas dissimilar loops correlated with strong transmission barriers. We then classified literature data on cross-species transmission according to the 170S/N polymorphism. Transmission barriers were generally low between species with the same amino acid residue in position 170 and high between those with different residues. These findings point to a triggering role of the local beta2-alpha2 loop structure for prion transmissibility between different species.

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45 citations in Web of Science®
48 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2010
Deposited On:14 Jan 2011 20:07
Last Modified:28 Nov 2013 00:53
Publisher:American Society for Clinical Investigation
ISSN:0021-9738
Publisher DOI:10.1172/JCI42051
PubMed ID:20551516

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