Estimation from moments measurements for amyloid depolymerisation

JOURNAL OF THEORETICAL BIOLOGY

卷:397

Article

Armiento, Aurora^1,2,3,4  Doumic, Marie²  Moireau, Philippe^3,4  Rezaei, H.⁵ 

[1] Univ Paris Diderot, Sorbonne Paris Cite, Lab JL Lions, Inria,UMR CNRS 7598, Paris, France

[2] Univ Paris 06, Sorbonne Univ, Inria, Lab JL Lions UMR CNRS 7598, Paris, France

[3] Inria, Campus Ecole Polytech, F-91128 Palaiseau, France

[4] Univ Paris Saclay, Campus Ecole Polytech, F-91128 Palaiseau, France

[5] INRA, Virol & Immunol Mol, F-78352 Jouy En Josas, France

关键词: Amyloid;    Prion;    Protein stability;    Oligomer;    Transport equation;    State estimation;    Inverse problem;    Data assimilation;   

DOI  :  10.1016/j.jtbi.2016.02.037

来源: Elsevier

【 摘 要 】

Estimating reaction rates and size distributions of protein polymers is an important step for understanding the mechanisms of protein misfolding and aggregation, a key feature for amyloid diseases. This study aims at setting this framework problem when the experimental measurements consist in the time dynamics of a moment of the population (i.e. for instance the total polymerised mass, as in Thioflavin T measurements, or the second moment measured by Static Light Scattering). We propose a general methodology, and we solve the problem theoretically and numerically in the case of a depolymerising system. We then apply our method to experimental data of depolymerising oligomers, and conclude that smaller aggregates of ovPrP protein should be more stable than larger ones. This has an important biological implication, since it is commonly admitted that small oligomers constitute the most cytotoxic species during prion misfolding process. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

Free