Item type:Thesis, Open Access

Interferenz in Signaltransduktionswege als therapeutischer Ansatz bei Prionkrankheiten

Thumbnail Image

Files

dae.pdf (7.16 MB)

Date

2005-09-09

relationships.isAuthorOf

Publisher

Philipps-Universität Marburg
DOI

item.page.supervisor-of-thesis

Abstract

The conversion of the cellular prion protein (PrPc) into pathologic PrPSc and the accumulation of aggregated PrPSc are hallmarks of prion diseases. A variety of experimental approaches to interfere with prion conversion have been reported. The aim of this work was to investigate whether interference with intracellular signalling events has an impact on this conversion process. Therefore, about 50 inhibitors of specific signalling pathways were screened in prion-infected cells for their capacity to affect prion conversion. The tyrosine kinase inhibitor STI571 was highly effective against PrPSc propagation, with an IC50 of less than 1 µM. STI571 cleared prion-infected cells time- and dose-dependently from PrPSc without influencing biogenesis, localization or biochemical features of PrPc. Interestingly, this compound did not interfere with the de novo formation of PrPSc but mainly activated the lysosomal degradation of pre-existing PrPSc, lowering the half-life time of PrPSc from >24 hours to <9 hours. The data indicate that among those kinases known to be inhibited by STI571, c-Abl is the most probable target responsible for the observed anti-prion effect. Taken together, treatment with STI571 profoundly activates the lysosomal degradation of PrPSc. Therefore, substances specifically interfering with cellular signalling pathways might represent a novel class of anti-prion compounds.

Review

Metadata

Contributors
Supervisor:
Dates
Created: 2005Issued: 2005-09-09Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2005.0396
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Neurodegenerative ErkrankungenSignaltransductionPrion diseasePrionNeurodegenerationPrion Protein
DFG-subjects
SignaltransduktionPrionproteinPrionkrankheitPrion
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2005.0396
show more
Ertmer, Alexa (130323659): Interferenz in Signaltransduktionswege als therapeutischer Ansatz bei Prionkrankheiten. : Philipps-Universität Marburg 2005-09-09. DOI: https://doi.org/10.17192/z2005.0396.

License

item.page.license.under-copyright
This item has been published with the following license: In Copyright