title: Estimation from moments measurements for amyloid depolymerisation.
abstract: 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.
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Lab. J.L. Lions, UMR CNRS 7598, Inria , Paris, France; Sorbonne Universités, Inria, UPMC Univ Paris 06, Lab. J.L. Lions UMR CNRS 7598, Paris, France; Inria and Université Paris-Saclay, Campus de l׳Ecole Polytechnique, 91128 Palaiseau, France. Electronic address: aurora.armiento@inria.fr.
authors.forename: Aurora
authors.initials: A
authors.lastname: Armiento
authors.affiliation: Sorbonne Universités, Inria, UPMC Univ Paris 06, Lab. J.L. Lions UMR CNRS 7598, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Doumic
authors.affiliation: Inria and Université Paris-Saclay, Campus de l׳Ecole Polytechnique, 91128 Palaiseau, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moireau
authors.affiliation: Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, F-78352 Jouy-en-Josas, France.
authors.forename: H
authors.initials: H
authors.lastname: Rezaei
mesh_terms: D000465:Algorithms; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D003198:Computer Simulation; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008962:Models, Theoretical; D019636:Neurodegenerative Diseases / Q000378:metabolism; D058105:Polymerization; D011328:Prions / Q000737:chemistry / Q000378:metabolism; D066329:Protein Aggregates; D017510:Protein Folding; D055503:Protein Multimerization
chemical_list: D000682:Amyloid; D011328:Prions; D066329:Protein Aggregates
keywords: Amyloid; Data assimilation; Inverse problem; Oligomer; Prion; Protein stability; State estimation; Transport equation