NR AXRD
AU Lenuzza,N.; Eterpi,M.; Charveriat,M.; Calvez,V.; Oelz,D.; Perthame,B.; Laurent,P.; Deslys,J.P.; Mouthon,F.
TI A Theoretical Size Structured Model of Prion Replication
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Protein Misfolding P01.39
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
The mechanisms of PrPsc replication are poorly characterised. Mathematical models can help us understand prion multiplication by testing which mecanisms best fit experimental data. We have developed a mathematical model to investigate how the infectivity of prion fibrils can explain their observed size distribution.
Our model is based on an existing mathematical model of prion replication by a nucleated polymerization mechanism, described by Masel (Biophysical Chemistry 77, 1999) and studied by other teams. In this model, it is assumed that the infectious particle is an aggregate of several PrPsc proteins. Aggregates can replicate by breaking into smaller polymers. They also can lengthen by the addition of a PrPc monomer (which is then transformed into PrPsc). The existing formulations of the model consider that every aggregate has the same ability to convert PrPc into PrPsc, regardless of its size. This assumption seems to be in contradiction with experimental results published by Silveira et al (Nature 437, 2005), in which aggregates consisting of 14 to 28 prion proteins appear to be the most infectious particles. We allowed the transformation rate of each infectious particle to be size-dependant, and we analysed in what way the size distribution of this rate could influence the kinetics of prion replication. Numerical simulations are in progress to test the conditions that best correspond to the experimental data published by Silveira. Such a model provides a powerful tool to investigate the nature of the infectious agent responsible for prion diseases, and the mechanisms of prion replication.
AD N. Lenuzza, M. Eterpi, M. Charveriat, J.P. Deslys, F. Mouthon, CEA/DSV/IMETI/SEPIA, France; V. Calves, D. Oelz, B. Perthame, Ecole Normale Supérieure, Département de Mathématiques et Applications, France; P. Laurent, Ecole Centrale Paris, MAS, France
SP englisch
PO Schottland