title: Strain-dependent profile of misfolded prion protein aggregates.
abstract: 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.
authors.affiliation: Mitchell Center for Alzheimer's disease and Related Brain Disorders, Dept. of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Morales
authors.affiliation: Mitchell Center for Alzheimer's disease and Related Brain Disorders, Dept. of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.|Innovative Drug Research Centre, Chongqing University, Chongqing 401331, China.
authors.forename: Ping Ping
authors.initials: PP
authors.lastname: Hu
authors.affiliation: Mitchell Center for Alzheimer's disease and Related Brain Disorders, Dept. of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.|Universidad de los Andes, Facultad de Medicina, Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Duran-Aniotz
authors.affiliation: Mitchell Center for Alzheimer's disease and Related Brain Disorders, Dept. of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Moda
authors.affiliation: Mitchell Center for Alzheimer's disease and Related Brain Disorders, Dept. of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Diaz-Espinoza
authors.affiliation: Mitchell Center for Alzheimer's disease and Related Brain Disorders, Dept. of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.|Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing, 100069, China.
authors.forename: Baian
authors.initials: B
authors.lastname: Chen
authors.affiliation: Mitchell Center for Alzheimer's disease and Related Brain Disorders, Dept. of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.|Universidad de los Andes, Facultad de Medicina, Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile.
authors.forename: Javiera
authors.initials: J
authors.lastname: Bravo-Alegria
authors.affiliation: BioMET and Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Natallia
authors.initials: N
authors.lastname: Makarava
authors.affiliation: BioMET and Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ilia V
authors.initials: IV
authors.lastname: Baskakov
authors.affiliation: Mitchell Center for Alzheimer's disease and Related Brain Disorders, Dept. of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.|Universidad de los Andes, Facultad de Medicina, Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Soto
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002499:Centrifugation, Density Gradient; D005260:Female; D015870:Gene Expression; D008647:Mesocricetus; D018620:PrPSc Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological / Q000378:metabolism* / Q000473:pathology; D011487:Protein Conformation; D017510:Protein Folding; D059748:Proteolysis; D013045:Species Specificity
chemical_list: D018620:PrPSc Proteins; D066329:Protein Aggregates