TY - JOUR T1 - Investigating the Conformational Stability of Prion Strains through a Kinetic Replication Model JF - PLoS Comput Biol 2009;5(7): e1000420 Y1 - 2009 A1 - Mattia Zampieri A1 - Giuseppe Legname A1 - Claudio Altafini AB - Prion proteins are known to misfold into a range of different aggregated forms, showing different phenotypic and pathological states. Understanding strain specificities is an important problem in the field of prion disease. Little is known about which PrPSc structural properties and molecular mechanisms determine prion replication, disease progression and strain phenotype. The aim of this work is to investigate, through a mathematical model, how the structural stability of different aggregated forms can influence the kinetics of prion replication. The model-based results suggest that prion strains with different conformational stability undergoing in vivo replication are characterizable in primis by means of different rates of breakage. A further role seems to be played by the aggregation rate (i.e. the rate at which a prion fibril grows). The kinetic variability introduced in the model by these two parameters allows us to reproduce the different characteristic features of the various strains (e.g., fibrils\\\' mean length) and is coherent with all experimental observations concerning strain-specific behavior. PB - PLoS UR - http://hdl.handle.net/1963/3989 U1 - 413 U2 - Mathematics U3 - Functional Analysis and Applications ER -