Therapeutical approaches for prion diseases and characterization of recombinant prion strains from different perspectives

Abstract

Prion diseases are rare and fatal neurodegenerative disorders for which there is no cure or treatment. They are caused by infectious proteins that result from the misfolding of the cellular prion protein, PrPC, into its pathogenic form, PrPSc. Furthermore, PrPSc can appear as conformational variants called strains that exhibit distinct phenotypes and could present resistance to anti-prion compounds. This thesis aims to assess three different therapeutic candidates in a fast murine model of prion disease to tackle these disorders from different aspects of their biology. Additionally, due to the role of prion strains in drug resistance and their biochemical and structural interest, diverse recombinant prion strains were characterized in this thesis using biological, biochemical, and biophysical methods.