LMU München
Fakultät für Physik



(c) 2002 BMO

"Piperazine derivatives inhibit PrP/PrPres propagation in vitro and in vivo"
Fabienne Leidel, Martin Eiden, Markus Geissen, Thomas Hirschberger, Paul Tavan, Armin Giese, Hans A. Kretzschmar, Hermann Schätzl, and Martin H. Groschup
Biochem. Biophys. Res. Commun. 445, 23-29 (2014).

Prion diseases are fatal neurodegenerative disorders, which are not curable and no effective treatment exists so far. The major neuropathological change in diseased brains is the conversion of the normal cellular form of the prion protein PrPC into a disease-associated isoform PrPSc. PrPSc accumulates into multimeres and fibrillar aggregates, which leads to the formation of amyloid plaques. Increasing evidence indicates a fundamental role of PrPSc species and its aggregation in the pathogenesis of prion diseases, which initiates the pathological cascade and leads to neurodegeneration accompanied by spongiform changes. In search of compounds that have the potential to interfere with PrPSc formation and propagation, we used a cell based assay for the screening of potential aggregation inhibitors. The assay deals with a permanently prion infected cell line that was adapted for a high-throughput screening of a compound library composed of 10.000 compounds (DIVERset 2). We could detect 6 different classes of highly potent inhibitors of PrPSc propagation in vitro and identified a new class of piperazine derivatives as a new lead structure, which increased incubation time of scrapie infected mice.

BMO authors (in alphabetic order):
Thomas Hirschberger
Paul Tavan

Assoziierte Projekte:
Molecular Modeling and Pattern Recognition for Computational Analysis and Support of Screening Experiments Aiming at the Development of Anti-TSE pharmaceuticals

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Letzte Änderung: 2016-09-14 11:34