A study in nucleated polymerization models of protein aggregation

The nucleated polymerization model is a mathematical framework that has been applied to aggregation and fragmentation processes in both the discrete and continuous setting. In particular, this model has been the canonical framework for analyzing the dynamics of protein aggregates arising in prion and amyloid diseases such as as Alzheimer's and Parkinson's disease. We present an explicit steady-state solution to the aggregate size distribution governed by the discrete nucleated polymerization equations. Steady-state solutions have been previously obtained under the assumption of continuous aggregate sizes; however, the discrete solution allows for direct computation and parameter inference, as well as facilitates estimates on the accuracy of the continuous approximation.

[1]  J. Griffith,et al.  Nature of the Scrapie Agent: Self-replication and Scrapie , 1967, Nature.

[2]  Suzanne S. Sindi,et al.  A Size Threshold Limits Prion Transmission and Establishes Phenotypic Diversity , 2010, Science.

[3]  R. Finke,et al.  Protein aggregation kinetics, mechanism, and curve-fitting: a review of the literature. , 2009, Biochimica et biophysica acta.

[4]  Thorsten Pöschel,et al.  Kinetics of prion growth. , 2003, Biophysical journal.

[5]  Thierry Goudon,et al.  Scaling limit of a discrete prion dynamics model , 2009, 0907.2297.

[6]  Jonathan S. Weissman,et al.  The physical basis of how prion conformations determine strain phenotypes , 2006, Nature.

[7]  Pierre Gabriel,et al.  The shape of the polymerization rate in the prion equation , 2010, Math. Comput. Model..

[8]  M A Nowak,et al.  Quantifying the kinetic parameters of prion replication. , 1999, Biophysical chemistry.

[9]  D. Hall,et al.  Computational modeling of the relationship between amyloid and disease , 2012, Biophysical Reviews.

[10]  Suzanne S. Sindi,et al.  Prion dynamics and the quest for the genetic determinant in protein-only inheritance. , 2009, Current opinion in microbiology.

[11]  S. Radford,et al.  Amyloid fibril length distribution quantified by atomic force microscopy single-particle image analysis , 2009, Protein engineering, design & selection : PEDS.

[12]  Thierry Goudon,et al.  The Beker-Döring System and Its Lifshitz-Slyozov Limit , 2002, SIAM J. Appl. Math..

[13]  Glenn F. Webb,et al.  Analysis of a model for the dynamics of prions II , 2005 .

[14]  Adriano Aguzzi,et al.  Prions: protein aggregation and infectious diseases. , 2009, Physiological reviews.

[15]  Martin A. Nowak,et al.  Prion infection dynamics , 1998 .

[16]  Laurent Pujo-Menjouet,et al.  A mathematical analysis of the dynamics of prion proliferation. , 2006, Journal of theoretical biology.

[17]  J. Collinge Prion diseases of humans and animals: their causes and molecular basis. , 2001, Annual review of neuroscience.

[18]  Philippe Laurençot,et al.  From the discrete to the continuous coagulation–fragmentation equations , 2002, Proceedings of the Royal Society of Edinburgh: Section A Mathematics.

[19]  Laurent Pujo-Menjouet,et al.  Analysis of a model for the dynamics of prions , 2005 .