According to the protein-only hypothesis [ 5], an abnormal PrP isoform is the principal, if not the sole, component of the transmissible prion, with prion propagation occurring through PrPSc acting to replicate itself with high fidelity by recruiting endogenous PrPC [ 1, 2, 6, 7].
Once formed, PrPSc self-perpetuates by propagating as a template its fold to PrPC [1],[2].
The pathogenesis of prion diseases is based on the presence of PrPSc, a protease-resistant isoform of the normal cellular prion protein called PrPC [1], [2].
Prion diseases are fatal neurodegenerations of mammals featured by the apparition of misfolded and aggregated forms of the cellular prion protein (PrPC) [1],[2].
The prominent, if not only, component of prions is a misfolded conformer (PrPSc) of a constitutive sialoglycoprotein, the cellular prion protein (PrPC) [1].
The cause of spongiform encephalopathy in Creutzfeldt-Jacob disease (CJD), scrapie in sheep or bovine spongiform encephalopathy (BSE) is an abnormal conformational isoform (PrPsc) of the Prnp gene product PrPc [1] [4].
PrPSc is covalently indistinguishable from PrPC [1], [7], [16] but can be differentiated from PrPC by its partial resistance to proteolysis and its marked insolubility in detergents [1], [7].
Prions, the infectious agents associated with transmissible spongiform encephalopathies such as scrapie in sheep, chronic wasting disease (CWD) in deer and elk, bovine spongiform encephalopathy (BSE), and Creutzfeldt-Jakob disease (CJD) in humans, are primarily comprised of PrPSc, a protease-resistant misfolded isoform of the cellular prion protein PrPC [1].
PrPsc is more resistant to protease digestion than PrPc [5], [13] [16].
Mechanistically, GAGs have been proposed to act as scaffolds to support the misfolding of PrPC [25].
