Title: Effects of post-translational modifications on prion protein aggregation and the propagation of scrapie-like characteristics in vitro
Authors: Dear, Denise V ×
Young, Duncan S
Kazlauskaite, Jurate
Meersman, Filip
Oxley, David
Webster, Judith
Pinheiro, Teresa J T
Gill, Andrew C
Bronstein, Igor
Lowe, Christopher R #
Issue Date: 27-Jul-2007
Publisher: Elsevier
Series Title: Biochimica et Biophysica Acta. Proteins and Proteomics vol:1774 issue:7 pages:792-802
Abstract: Prion diseases, or transmissible spongiform encephalopathies (TSEs) are typically characterised by CNS accumulation of PrP(Sc), an aberrant conformer of a normal cellular protein PrP(C). It is thought PrP(Sc) is itself infectious and the causative agent of such diseases. To date, no chemical modifications of PrP(Sc), or a sub-population thereof, have been reported. In this study we have investigated whether chemical modification of amino acids within PrP might cause this protein to exhibit aberrant properties and whether these properties can be propagated onto unmodified prion protein. Of particular interest were post-translational modifications resulting from physiological conditions shown to be associated with TSE disease. Here we report that in vitro exposure of recombinant PrP to conditions that imitate the end effects of oxidative/nitrative stress in TSE-infected mouse brains cause the protein to adopt many of the physical characteristics of PrP(Sc). Most interestingly, these properties could be propagated onto unmodified PrP protein when the modified protein was used as a template. These data suggest that post-translational modifications of PrP might contribute to the initiation and/or propagation of prion protein-associated plaques in vivo during prion disease, thereby high-lighting novel biochemical pathways as possible therapeutic targets for these conditions.
ISSN: 1570-9639
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Imaging and Photonics
× corresponding author
# (joint) last author

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