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, host-encoded 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 surface-anchored glycoprotein whose function is not well characterized [3]. PrPSc is derived from PrPC in a posttranslational 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].
