title: Quality control system response to stochastic growth of amyloid fibrils.
abstract: We introduce a stochastic model describing aggregation of misfolded proteins and degradation by the protein quality control system in a single cell. Aggregate growth is contrasted by the cell quality control system, that attacks them at different stages of the growth process, with an efficiency that decreases with their size. Model parameters are estimated from experimental data. Two qualitatively different behaviors emerge: a homeostatic state, where the quality control system is stable and aggregates of large sizes are not formed, and an oscillatory state, where the quality control system periodically breaks down, allowing for formation of large aggregates. We discuss how these periodic breakdowns may constitute a mechanism for the development of neurodegenerative diseases.
authors.affiliation: Dept. de Fisica i Eng. Nuclear, Universitat Politecnica de Catalunya Edif. GAIA, Rambla Sant Nebridi s/n, 08222 Terrassa, Barcelona, Spain. simone.pigolotti@upc.edu
authors.forename: Simone
authors.initials: S
authors.lastname: Pigolotti
authors.forename: Ludvig
authors.initials: L
authors.lastname: Lizana
authors.forename: Daniel
authors.initials: D
authors.lastname: Otzen
authors.forename: Kim
authors.initials: K
authors.lastname: Sneppen
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D006706:Homeostasis; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D059748:Proteolysis; D013269:Stochastic Processes
chemical_list: D000682:Amyloid