Quantifying the kinetic parameters of prion replication

Joanna Masel, Vincent A.A. Jansen, Martin A. Nowak

Research output: Contribution to journalArticlepeer-review

176 Scopus citations

Abstract

The mechanism of protein-only prion replication is controversial. A detailed mathematical model of prion replication by nucleated polymerisation is developed, and its parameters are estimated from published data. PrP-res decay is around two orders of magnitude slower than PrP-sen decay, a plausible ratio of two parameters estimated from very different experiments. By varying the polymer breakage rate, we reveal that systems of short polymers grow the fastest. Drugs which break polymers could therefore accelerate disease progression. Growth in PrP-res seems slower than growth in infectious titre. This can be explained either by a novel hypothesis concerning inoculum clearance from a newly infected brain, or by the faster growth of compartments containing smaller polymers. The existence of compartments can also explain why prion growth sometimes reaches a plateau. Published kinetic data are all compatible with our mathematical model, so the nucleated polymerisation hypothesis cannot be ruled out on dynamic grounds. Copyright (C) 1999 Elsevier Science B.V. All rights reserved.

Original languageEnglish (US)
Pages (from-to)139-152
Number of pages14
JournalBiophysical Chemistry
Volume77
Issue number2-3
DOIs
StatePublished - Mar 29 1999
Externally publishedYes

Keywords

  • Mathematical model
  • Nucleated polymerisation
  • Prion diseases
  • Replication mechanism

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Organic Chemistry

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