Objective
Prion diseases are a group of transmissible, neurodegenerative maladies, which include bovine spongiform encepholopathy (BSE) of cattle, Creutzfeldt-Jakob disease, Gerstmann-Straeussler syndrome and kuru in man as well as scrapie in sheep and goats. It has been shown that BSE is transmissible to mice and that one protease resistant prion protein accumulates in the brains of infected cattle. The prion protein, PrPSc, and its cellular isoform, PrPc, are encoded by the same chromosomal gene. Research is underway to elucidate the protein or virus etiology of BSE and related diseases, the mechanism of infection of cells with PrPSc (adsorption and uptake of PrPSc into cells), the mechanisms of formation of intracellular aggregates of PrPSc, the effect of PrPSc on intracellular signal transduction processes, the mechanism of replication of PrPSc (translation and posttranslational level) and possible strategies for therapy or prophylaxis of infections with PrPSc.
In preliminary studies on the kinetics of expression of prion protein in uninfected and scrapie infected N2a mouse neuroblastoma cells, PrP protein was observed in the nucleus and mostly in the nucleoli of ScN2a cells. Analysis of the PrP messenger ribonucleic acid (mRNA) levels both in N2a and in ScN2a cells, using complementary deoxyribonucleic acid (cDNA) encoding PrPc, revealed no marked alteration of the mRNA steady state level. In a further set of experiments, the accumulation of transcripts coding for prion protein in human astrocytes during infection with human immunodeficiency virus-1 (HIV-1) has been studied. These studies have revealed that the mRNA of PrP contains stem loop structures which are very similar to the HIV-1 cis acting sequence TAR within the long terminal repeat (LTR), and that Tat binds to TAR and PrP RNA. It was also demonstrated that infection of astrocytes with HIV-1 resulted in an increased level of PrP mRNA. First indications have been obtained that cells can be protected against PrPSc infection by treatment with special compounds and this is the subject of a patent application.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics RNA
- agricultural sciences animal and dairy science domestic animals animal husbandry
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Programme(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Coordinator
55099 MAINZ
Germany
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