TY - JOUR
T1 - Role of prion replication in the strain-dependent brain regional distribution of prions
AU - Hu, Ping Ping
AU - Morales, Rodrigo
AU - Duran-Aniotz, Claudia
AU - Moreno-Gonzalez, Ines
AU - Khan, Uffaf
AU - Soto, Claudio
N1 - Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2016/6/10
Y1 - 2016/6/10
N2 - 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 PrPSc. Our data show that these strains have different profiles of PrP deposition along the brain. These patterns of accumulation, which were independent of regional PrPC 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 PrPC present in each part of the brain. Our results suggest that the variable regional distribution of PrPSc 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.
AB - 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 PrPSc. Our data show that these strains have different profiles of PrP deposition along the brain. These patterns of accumulation, which were independent of regional PrPC 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 PrPC present in each part of the brain. Our results suggest that the variable regional distribution of PrPSc 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.
UR - http://www.scopus.com/inward/record.url?scp=84974589302&partnerID=8YFLogxK
U2 - 10.1074/jbc.M115.681791
DO - 10.1074/jbc.M115.681791
M3 - Article
C2 - 27056328
AN - SCOPUS:84974589302
SN - 0021-9258
VL - 291
SP - 12880
EP - 12887
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 24
ER -