title: Role of Prion Replication in the Strain-dependent Brain Regional Distribution of Prions.
abstract: One intriguing feature of prion diseases is their strain variation. Prion strains are differentiated by the clinical consequences they generate in the host, their biochemical properties, and their potential to infect other animal species. The selective targeting of these agents to specific brain structures have been extensively used to characterize prion strains. However, the molecular basis dictating strain-specific neurotropism are still elusive. In this study, isolated brain structures from animals infected with four hamster prion strains (HY, DY, 139H, and SSLOW) were analyzed for their content of protease-resistant PrP(Sc) Our data show that these strains have different profiles of PrP deposition along the brain. These patterns of accumulation, which were independent of regional PrP(C) production, were not reproduced by in vitro replication when different brain regions were used as substrate for the misfolding-amplification reaction. On the contrary, our results show that in vitro replication efficiency depended exclusively on the amount of PrP(C) present in each part of the brain. Our results suggest that the variable regional distribution of PrP(Sc) in distinct strains is not determined by differences on prion formation, but on other factors or cellular pathways. Our findings may contribute to understand the molecular mechanisms of prion pathogenesis and strain diversity.
authors.affiliation: From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas 77030,; Innovative Drug Research Centre, Chongqing University, Chongqing 401331, China, and.
authors.forename: Ping Ping
authors.initials: PP
authors.lastname: Hu
authors.affiliation: From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas 77030.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Morales
authors.affiliation: From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas 77030,; 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: From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas 77030.
authors.forename: Ines
authors.initials: I
authors.lastname: Moreno-Gonzalez
authors.affiliation: From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas 77030.
authors.forename: Uffaf
authors.initials: U
authors.lastname: Khan
authors.affiliation: From the Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, Texas 77030,; Universidad de los Andes, Facultad de Medicina, Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile. Electronic address: Claudio.Soto@uth.tmc.edu.
authors.forename: Claudio
authors.initials: C
authors.lastname: Soto
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000821:virology; D006224:Cricetinae; D005260:Female; D054884:Host-Pathogen Interactions; D008647:Mesocricetus; D018620:PrPSc Proteins / Q000737:chemistry / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism* / Q000821:virology; D011328:Prions / Q000145:classification / Q000378:metabolism* / Q000472:pathogenicity; D017510:Protein Folding; D013045:Species Specificity; D014774:Virulence; D014779:Virus Replication
chemical_list: D018620:PrPSc Proteins; D011328:Prions
keywords: neurodegenerative disease; prion; prion disease; protein aggregation; protein misfolding