Prion Formation, but Not Clearance, Is Supported by Protein Misfolding Cyclic Amplification

Prion. 2014;8(6):415-20. doi: 10.4161/19336896.2014.983759.

Abstract

Prion diseases are fatal transmissible neurodegenerative disorders that affect animals including humans. The kinetics of prion infectivity and PrP(Sc) accumulation can differ between prion strains and within a single strain in different tissues. The net accumulation of PrP(Sc) in animals is controlled by the relationship between the rate of PrP(Sc) formation and clearance. Protein misfolding cyclic amplification (PMCA) is a powerful technique that faithfully recapitulates PrP(Sc) formation and prion infectivity in a cell-free system. PMCA has been used as a surrogate for animal bioassay and can model species barriers, host range, strain co-factors and strain interference. In this study we investigated if degradation of PrP(Sc) and/or prion infectivity occurs during PMCA. To accomplish this we performed PMCA under conditions that do not support PrP(Sc) formation and did not observe either a reduction in PrP(Sc) abundance or an extension of prion incubation period, compared to untreated control samples. These results indicate that prion clearance does not occur during PMCA. These data have significant implications for the interpretation of PMCA based experiments such as prion amplification rate, adaptation to new species and strain interference where production and clearance of prions can affect the outcome.

Keywords: prion clearance; prion disease; protein misfolding cyclic amplification.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / metabolism
  • Cell-Free System
  • Male
  • Mesocricetus
  • PrPSc Proteins / metabolism
  • Prion Diseases / metabolism
  • Prions / chemistry*
  • Protein Folding*

Substances

  • PrPSc Proteins
  • Prions