Prion Protein Strain Diversity and Disease Pathology

Abstract

The infectious agents, prions, are composed mainly of conformational isomers of the cellular prion protein (PrPc) in its abnormal accumulated scrapie forms (PrPSc). The distinct prion isolates or strains have been associated with different PrPSc prion protein conformations and patterns of glycosylation and are associated with disease progression and severity. In humans, sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form and has been divided into six subtypes, based on PrPSc electrophoretic mobility and allelic varia- tion at codon 129, among which sCJD MM1 and sCJD VV2 are the two most commonly occurring subtypes with known clinical manifestations. The strain- specific response of PrPSc suggests both the molecular classification and the pathogenesis of prion diseases along with posttranslational modification of PrP in humans and animals.