TY - JOUR
T1 - Strain-dependent profile of misfolded prion protein aggregates
AU - Morales, Rodrigo
AU - Hu, Ping Ping
AU - Duran-Aniotz, Claudia
AU - Moda, Fabio
AU - Diaz-Espinoza, Rodrigo
AU - Chen, Baian
AU - Bravo-Alegria, Javiera
AU - Makarava, Natallia
AU - Baskakov, Ilia V.
AU - Soto, Claudio
N1 - Funding Information:
The authors would like to thank Dr. Jason Bartz for providing hamster prion strains specimens. We would also like to thank Mrs. Andrea Flores-Ramirez for animal care and help in the assessment of clinical signs, and Mrs. Maria-Jose Liberona and Dr. Charles Mays for critical review of this manuscript. This work was supported in part by NIH grant R01 NS049173 to CS and NIH grant NS045585 to IVB.
PY - 2016/2/15
Y1 - 2016/2/15
N2 - Prions are composed of the misfolded prion protein (PrP Sc) organized in a variety of aggregates. An important question in the prion field has been to determine the identity of functional PrP Sc aggregates. In this study, we used equilibrium sedimentation in sucrose density gradients to separate PrP Sc aggregates from three hamster prion strains (Hyper, Drowsy, SSLOW) subjected to minimal manipulations. We show that PrP Sc aggregates distribute in a wide range of arrangements and the relative proportion of each species depends on the prion strain. We observed a direct correlation between the density of the predominant PrP Sc aggregates and the incubation periods for the strains studied. The relative presence of PrP Sc in fractions of different sucrose densities was indicative of the protein deposits present in the brain as analyzed by histology. Interestingly, no association was found between sensitivity to proteolytic degradation and aggregation profiles. Therefore, the organization of PrP molecules in terms of the density of aggregates generated may determine some of the particular strain properties, whereas others are independent from it. Our findings may contribute to understand the mechanisms of strain variation and the role of PrP Sc aggregates in prion-induced neurodegeneration.
AB - Prions are composed of the misfolded prion protein (PrP Sc) organized in a variety of aggregates. An important question in the prion field has been to determine the identity of functional PrP Sc aggregates. In this study, we used equilibrium sedimentation in sucrose density gradients to separate PrP Sc aggregates from three hamster prion strains (Hyper, Drowsy, SSLOW) subjected to minimal manipulations. We show that PrP Sc aggregates distribute in a wide range of arrangements and the relative proportion of each species depends on the prion strain. We observed a direct correlation between the density of the predominant PrP Sc aggregates and the incubation periods for the strains studied. The relative presence of PrP Sc in fractions of different sucrose densities was indicative of the protein deposits present in the brain as analyzed by histology. Interestingly, no association was found between sensitivity to proteolytic degradation and aggregation profiles. Therefore, the organization of PrP molecules in terms of the density of aggregates generated may determine some of the particular strain properties, whereas others are independent from it. Our findings may contribute to understand the mechanisms of strain variation and the role of PrP Sc aggregates in prion-induced neurodegeneration.
UR - http://www.scopus.com/inward/record.url?scp=84958260195&partnerID=8YFLogxK
U2 - 10.1038/srep20526
DO - 10.1038/srep20526
M3 - Article
C2 - 26877167
AN - SCOPUS:84958260195
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 20526
ER -