Estimation from Moments Measurements for Amyloid Depolymerisation
Résumé
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 (\emph{i.e.} for instance the total polymerised mass, as in Thioflavine 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 degrading 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.
Origine | Fichiers produits par l'(les) auteur(s) |
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