Mar 5, 2013

Frameshifted prion proteins as pathological agents: quantitative considerations

Journal of Theoretical Biology
P R Wills

Abstract

A quantitatively consistent explanation for the titres of infectivity found in a variety of prion-containing preparations is provided on the basis that the ætiological agents of transmissible spongiform encephalopathy comprise a very small population fraction of prion protein (PrP) variants, which contain frameshifted elements in their N-terminal octapeptide-repeat regions. A mechanism for the replication of frameshifted prions is described and calculations are performed to obtain estimates of the concentration of these PrP variants in normal and infected brain, as well as their enrichment in products of protein misfolding cyclic amplification. These calculations resolve the lack of proper quantitative correlation between measures of infectivity and the presence of conformationally-altered, protease-resistant variants of PrP. Experiments, which could confirm or eventually exclude the role of frameshifted variants in the ætiology of prion disease, are suggested.

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Mentioned in this Paper

Biochemical Pathway
Tryptophan
Exertion
Molecular Helix
Bixa orellana (plant)
Terminally Ill
EIF2S1 wt Allele
Pellet Formation
EIF2S3 gene
Pathogenic Organism

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