Prion diseases are fatal and incurable spongiform encephalopathies that occur amongst mammals. The central pathological event is the misfolding of the cellular prion protein (PrP^C) into an amyloid, neurotoxic isoform called scrapie (PrP^Sc). PrP^Sc is the main, or sole, constituent of infectious prions. PrP^Sc resists cellular degradation and also induces misfolding of PrP^C via a process called conversion. Conversion seems to be an endocytotic event implicating auxiliary cellular cofactors interacting with PrP^C and/or PrP^Sc. The aim of this thesis is to decipher and modulate key events involved in prion conversion and cytopathology, by studying persistently scrapie infected murine neuronal cell cultures. This work shows that cell penetrating peptides derived from the prion protein (PrP-CPPs) can suppress cellular PrP^Sc levels. The PrP-CPPs assert these actions on two prion strains regardless of peptide configuration and do not inhibit any PrP-interaction with heparan sulfate (HS) proteoglycans (PG). A polybasic motif in the PrP-CPPs may interact with PrP^Sc, but the anti-prion effect is controlled by a signal peptide sequence. The PrP-CPPs represents a novel form of prion antagonizing compound. Prion-induced alterations in protein expression, cellular localization, activity and metabolism, designate putative mediators of disease or neuroprotective defence mechanisms. We report on interplay between the HSPG glypican-1 (Gpc-1) and scrapie-infection. Gpc-1 is aberrantly distributed in scrapie-infected cells and HS degradation by autocatalytic deaminative cleavage is elevated, suggestively in order to restrain PrP^Sc levels. Additionally, we demonstrate that scrapie-infection elevates the activity of Src family kinase members Src and Fyn, in part by affecting Src expression and Fyn membrane distribution. This causes an uncontrolled tyrosine phosphorylation which could contribute to neuronal loss in vivo.