Molecular mechanisms mediating neuronal cell death in experimental models of prion diseases, in vitro

In this chapter we will review the growing bulk of experimental observations regarding the modulation of intracellular pathways mediating the neuronal cell death in in vitro models of prion diseases. In particular the effects of the prion-derived peptide PrP106-126 in different cell culture models will be described. PrP106-126 represents the first experimental approach to the prion-dependent neurotoxicity that has now been largely accepted by the scientific community. This peptide, although incompletely, reproduces in vitro many of the biochemical and pathological characteristics of the PrP Sc, allowing a detailed analysis of the signal transduction mediating the prion toxicity. The analysis will be focused on the different intracellular pathways modulated by PrP106-126, or related peptides, to induce neuronal cell death in both primary neuronal cultures or neuronal-like cell lines, in relation with its the structural characteristics. In particular the effects of this peptide on the intracellular ion concentration, MAP kinase cascades and radical oxygen species generation will be discussed.