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Mechanisms of neuroinvasion by prions: molecular principles and present state of research


Brandner, S; Klein, M A; Aguzzi, A (2000). Mechanisms of neuroinvasion by prions: molecular principles and present state of research. Swiss Medical Weekly, 130(12):435-442.

Abstract

The prion was defined by Stanley Prusiner as the infectious agent that causes transmissible spongiform encephalopathies and equated with the prion protein PrPSc. Its cognate gene, Prnp, was identified by Charles Weissmann in Zurich, and shown to encode the host protein PrPC. Since the latter discovery, transgenic mice have contributed many important insights to the field of prion biology, including an understanding of the molecular basis of the species barrier for prions. By disrupting the Prnp gene, it was shown that an organism that lacks PrPC is resistant to infection by prions. Introduction of mutant PrP genes into PrP-deficient mice was used to investigate the structure-activity relationship of the PrP gene with regard to scrapie susceptibility. Ectopic expression of PrP in Prnp-knockout mice provided a useful strategy for the identification of host cells competent for prion replication. Finally, the availability of Prnp-knockout mice and transgenic mice overexpressing PrP allows selective reconstitution experiments aimed at expressing PrP in neurografts or in specific populations of hemato- and lymphopoietic cells. The latter studies have allowed us to clarify some of the mechanisms of prion spread and disease pathogenesis.

The prion was defined by Stanley Prusiner as the infectious agent that causes transmissible spongiform encephalopathies and equated with the prion protein PrPSc. Its cognate gene, Prnp, was identified by Charles Weissmann in Zurich, and shown to encode the host protein PrPC. Since the latter discovery, transgenic mice have contributed many important insights to the field of prion biology, including an understanding of the molecular basis of the species barrier for prions. By disrupting the Prnp gene, it was shown that an organism that lacks PrPC is resistant to infection by prions. Introduction of mutant PrP genes into PrP-deficient mice was used to investigate the structure-activity relationship of the PrP gene with regard to scrapie susceptibility. Ectopic expression of PrP in Prnp-knockout mice provided a useful strategy for the identification of host cells competent for prion replication. Finally, the availability of Prnp-knockout mice and transgenic mice overexpressing PrP allows selective reconstitution experiments aimed at expressing PrP in neurografts or in specific populations of hemato- and lymphopoietic cells. The latter studies have allowed us to clarify some of the mechanisms of prion spread and disease pathogenesis.

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3 citations in Web of Science®
3 citations in Scopus®
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Additional indexing

Other titles:Mechanismen der Neuroinvasion: molekulare Grundlagen und aktueller Stand der Forschung
Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:German
Date:25 March 2000
Deposited On:11 Feb 2008 12:26
Last Modified:05 Apr 2016 12:21
Publisher:EMH Swiss Medical Publishers
ISSN:0036-7672
Related URLs:http://www.smw.ch/dfe/set_archiv.asp
PubMed ID:10780058
Permanent URL: https://doi.org/10.5167/uzh-1919

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