Quaternary Structure Changes for PrP Predate PrP Downregulation and Neuronal Death During Progression of Experimental Scrapie Disease.

Prion diseases are fatal neurodegenerative diseases in mammals with the unique characteristics of misfolding and aggregation of the cellular prion protein (PrP) to the scrapie prion (PrP). Although neuroinflammation and neuronal loss feature within the disease process, the details of PrP/PrP molecular transition to generate different aggregated species, and the correlation between each species and sequence of cellular events in disease pathogenesis are not fully understood. In this study, using mice inoculated with the RML isolate of mouse-adapted scrapie as a model, we applied asymmetric flow field-flow fractionation to monitor PrP and PrP particle sizes and we also measured seeding activity and resistance to proteases.