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Biochemical properties of highly neuroinvasive prion strains
Author(s) -
Sigurdson Christina J,
Bett Cyrus,
Joshi-Barr Shivanjali,
Lucero Melanie,
Trejo Margarita,
Liberski Pawel,
Kelly Jeffery,
Masliah Eliezer
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.398.10
Subject(s) - gene isoform , pathogenesis , congo red , prion protein , phenotype , neuropathology , amyloid (mycology) , strain (injury) , chemistry , biology , virology , biochemistry , gene , medicine , pathology , immunology , disease , anatomy , inorganic chemistry , organic chemistry , adsorption
Prion diseases are fatal neurodegenerative diseases caused by the conformational conversion of the cellular prion protein, PrP C , into an aggregated, β‐sheet rich isoform, PrP Sc . Prion pathogenesis can vary dramatically depending on the strain, thought to be conformational variants of PrP Sc , yet the structural basis for the differences in pathogenesis in unclear. Using an array of mouseadapted prion strains, here we define the neuropathology and biochemical features of prion strains that efficiently or poorly invade the CNS from their peripheral entry site. In brain sections, we find that the highly neuroinvasive prion strains primarily form diffuse aggregates that do not bind to the amyloid binding dye, Congo red. Biochemically these aggregates are conformationally unstable in denaturing conditions. These neuroinvasive strains also efficiently generate PrP Sc over short incubation periods. In contrast, the poorly neuroinvasive strains formed dense, Congo red binding aggregates that were conformationally stable. Our findings indicate that the most neuroinvasive, efficiently spreading strains are also the least conformationally stable, and support the concept that the unstable nature of the most rapidly converting prions may be a feature linked to their efficient spread into the CNS.