Quality control system response to stochastic growth of amyloid fibrils

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  • Simone Pigolotti, Dept. de Fisica i Eng. Nuclear, Universitat Politecnica de Catalunya Edif. GAIA, Spanien
  • Ludvig Lizana, Biokompleksitet, Danmark
  • Daniel Otzen
  • Kim Sneppen, Biokompleksitet, Danmark
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.
OriginalsprogEngelsk
TidsskriftF E B S Letters
Vol/bind587
Nummer9
Sider (fra-til)1405-1410
Antal sider6
ISSN0014-5793
DOI
StatusUdgivet - 2 maj 2013

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