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Content archived on 2024-04-30

Relationship between confirmation of Prp infectivity and pathogenicity of bovine spongiform and cephalopathy (BSE) as a bases for diagnosis

Objective



Transmissible spongiform encephalopathies (TSE) or prion diseases are a group of neurodegenerative afflictions which include Creutzfeldt-Jacob disease (CJD) in humans, scrapie in sheep and goats, and bovine spongi form encephalopathie (BSE) in cattle. In contrast to the many strains and PrP polymorphisms found in sheep, only one strain and one PrP polymorphism has so far been detected in cattle. In addition, BSE prions seem to be transmissible to humans orally, causing new variant CJD. So it is the important to monitor the frequency of prion disease in cattle since they are slaughtered for human consumption. Up to now, no reliable, specific test has been available for detecting prion disease in living animals.

The main objectives of this European group with partners from France, Germany and the UK are the determination of the molecular properties conformation and conformational transitions of normal prion protein PrPc, the BSE version PrPBSE and PrP-peptides of the bovine sequence. They will be compared with the corresponding properties known for scrapie and CJD to differentiate between general principles and BSE-specific features.

The partners will study the relationship between BSE infection, PrP-accumulation, PrP conformation, interacting ligands and the appearance of early markers, and thereby develop an optimal concept for a sensitive diagnosis.
A cell-culture system susceptible to BSE infection will be established. Specified antibodies and other PrP-interacting ligands such as RNA-aptamers will be studied systematically to differentiate between the normal and the disease-specific abnormal isoform of PrP. Until now a series of polyclonal anti-PrPBSE-peptide antibodies have been produced; furthermore RNA aptamerswere selected against PrPc and PrPsc. A specific and differential binding could be shown. To understand the neurodegeneration mechanism, the appearance of early markers induced by a BSE infection in neuronal cell cultures will be characterised. Therefore, single cell RT-PCR multiplex has been established to identify mRNA markers in single cells to determine early markers and steps of prion infection and pathogenicity.

Topic(s)

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Call for proposal

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Coordinator

HEINRICH-HEINE-UNIVERSITAET DUESSELDORF
EU contribution
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Address
Universitaetsstr. 1
40225 Düsseldorf
Germany

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Participants (5)