Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform ( PrPSc) of the host-encoded cellular prion protein ( PrPC). Human and ani...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 9; pp. 3065 - 3070 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
02.03.2004
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform ( PrPSc) of the host-encoded cellular prion protein ( PrPC). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrPScfragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called "species barrier" between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrPScaccumulation. In addition, Western blot analysis showed a PrPSctype with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE- PrPSc. Strikingly, the molecular signature of this previously undescribed bovine PrPScwas similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 To whom correspondence should be addressed. E-mail: salvatore.monaco@mail.univr.it. Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved December 23, 2003 This paper was submitted directly (Track II) to the PNAS office. C.C. and G.Z. contributed equally to this work. Abbreviations: TSE, transmissible spongiform encephalopathy, BSE, bovine spongiform encephalopathy; CJD, Creutzfeldt-Jakob disease; vCJD, variant CJD; sCJD, sporadic CJD; PrP, prion protein, PrPSc pathological PrP; BASE, bovine amyloidotic spongiform encephalopathy. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0305777101 |