A nanoparticle-based immobilization assay for prion-kinetics study

Prion diseases also called Transmissible Spongiform Encephalopathies (TSE) are a group of degenerative diseases that feature the pronounced accumulation, in certain brain regions, of a misfolded isomer PrPsc of the cellular prion protein (PrPc) [1-3]. Spongiform encephalopathy in cattle, scrapie in sheep, Gerstmann-Straussler Scheinker in human, and Creutzfied-Jacob disease are caused due to the misfolding of protein denoted as prion protein [1-4]. Understanding the basis of prion disease revolves around understanding how the normal protein, PrPc is converted into its abnormal form, PrPsc. Hypothesis suggest that prion infection is associated with a conformational transition between the two forms [1-5]. In a broader sense, prions are elements that impart and propagate variability through a multitude of conformations of normal cellular proteins [6]. However, the mechanism by which this conversion occurs is not clearly known. Cui et al. [6] and Spencer et al [7] proposed that this conversion involves a switch in the conformation from a structure rich in α-helix to the one rich in β-sheet through a spatial arrangement and molecule folding.Protein unfolding is associated with the disruption of interactions leading to a loss in the secondary structure (the fold of α-helices, β-strands and turns, and tertiary structure – the packing of the secondary structural elements and the amino acid side chains [8]). In the last two decades a fundamental concern that arose was on the issues of prion related diseases. For example, meat exported from UK has been banned by a number of countries as a precautionary measure against Bovine Spongiform Encephalopathy (BSE) after the major outbreak of mad cow disease in 1996. Although the cause of the infection remains unknown, it was suggested that meat and bone meal imported from other countries may have been incorporated into feed supplements before these countries could adopt a suitable feed control strategy [9]. In 2003, BSE was detected