Prion strain interactions are highly selective.
Various misfolded and aggregated neuronal proteins commonly coexist in neurodegenerative disease, but whether the proteins coaggregate and alter the disease pathogenesis is unclear. Here, we used mixtures of distinct prion strains, which are believed to differ in conformation, to test the hypothesis that two different aggregates interact and change the disease in vivo. We tracked two prion strains in mice histopathologically and biochemically, as well as by spectral analysis of plaque-bound PTAA (polythiophene acetic acid), a conformation-sensitive fluorescent amyloid ligand. We found that prion strains interacted in a highly selective and strain-specific manner, with (1) no interaction, (2) hybrid plaque formation, or (3) blockage of one strain by a second (interference). The hybrid plaques were maintained on additional passage in vivo and each strain seemed to maintain its original conformational properties, suggesting that one strain served only as a scaffold for aggregation of the second strain. These findings not only further our understanding of prion strain interactions but also directly demonstrate interactions that may occur in other protein aggregate mixtures.
Nilsson
K Peter R
KP
Department of Physics, Chemistry, and Biology, Linköping University, Linköping, Sweden.
Joshi-Barr
Shivanjali
S
Winson
Olivia
O
Sigurdson
Christina J
CJ
D000682:Amyloid; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011108:Polymers; D017096:Prion Diseases / Q000401:mortality / Q000473:pathology / Q000635:transmission* / Q000662:veterinary; D011328:Prions / Q000145:classification / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D012608:Scrapie; D012720:Severity of Illness Index; D012756:Sheep; D013045:Species Specificity; D013057:Spectrum Analysis / Q000379:methods; D013223:Statistics as Topic; D013329:Structure-Activity Relationship; D016019:Survival Analysis; D013876:Thiophenes
D000682:Amyloid; D005904:Glial Fibrillary Acidic Protein; D011108:Polymers; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; D013876:Thiophenes; C066730:polythiophene
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