ABSTRACT
Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurological disorders that include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, and chronic wasting disease (CWD) in cervids. A key event in prion diseases is the conversion of the cellular, hostencoded prion protein (PrPC) to its abnormal isoform (PrPSc) predominantly in the central nervous system of the infected host.1 There is increasing evidence that the major and possibly only component of the infectious agent is PrPSc or a prion protein (PrP) folding intermediate.2 PrPC is a cell surfaceanchored glycoprotein whose function is not well characterized.3 PrPSc is derived from PrPC in a post-translational process that appears to involve PrPC-PrPSc molecular interactions.4 The crucial role of PrPC expression in prion infection and PrPSc formation has been demonstrated in transgenic mice with an ablated PrP murine gene.5 Transgenic animals have since been used extensively to unravel the inuence
of specic PrP amino acid residues or domains on prion susceptibility.6-11
Kuru and the transmissible agents in dementias have been classied in a group of virus-induced slow infections that we have described as sub-acute spongiform virus encephalopathies because of the strikingly similar histopathological lesions they induce (Table 9.1).
