Fabrizio Tagliavini

Cytotoxicity of PrP Peptides

In prion disease, accumulation of PrPSc and PrP amyloid in the central nervous system (CNS) is accompanied by activation of microglial cells, hypertrophy and proliferation of astrocytes, and degeneration of neurons, leading to variable degrees of atrophy of the target regions. The temporal and anatomical correlation between PrPSc deposition and the development of neuropathological changes suggests that altered forms of the protein are responsible for the nerve cell degeneration and glial cell reaction [1-5]. In principle, one could directly test the toxic effect of PrPSc by applying the purified protein to neurons in culture. Although there have been several reports of such experiments [6-8], they are difficult to interpret because of uncertainties about the physical state of the PrPSc, since detergents needed to keep the protein in solution have to be removed before it can be applied to cell cultures. An alternative strategy is to analyze the effect on cultured neurons of synthetic peptides derived from the PrP sequence.

PrP Peptides as a Tool to Investigate the Pathogenesis of Prion Protein Amyloidoses

In prion diseases, abnormal isoforms of the prion protein (PrP) and PrP amyloid accumulate in the brain.1,2 At difference with normal PrP, the disease-specific PrP is resistant to protease digestion.1,2 The abnormal protein likely issues from protease-sensitive precursors following a post-translational modification involving a shift from α-helix to β-sheet secondary structure.3–5