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Quality control system response to stochastic growth of amyloid fibrils
Universitat Politecnica de Catalunya Edif. GAIA, Rambla Sant Nebridi s/n, 08222 Terrassa, Barcelona, Spain. (Dept. de Fisica i Eng. Nuclear,)
Umeå University, Faculty of Science and Technology, Department of Physics. (Icelab)
University of Aarhus, Gustav Wieds Vej 10C Aarhus C, Denmark. (iNANO, Department of Molecular Biology and Genetics Center for Insoluble Protein Structures (inSPIN))
Niels Bohr Institute. (Center for models of life)
2013 (English)In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 587, no 9, 1405-1410 p.Article in journal, Letter (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2013. Vol. 587, no 9, 1405-1410 p.
Keyword [en]
Protein aggregation, Neurodegenerative disease, Stochastic dynamics, Spiky oscillation, Proteasome–lysosome
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Research subject
URN: urn:nbn:se:umu:diva-70227DOI: 10.1016/j.febslet.2013.03.018OAI: diva2:620435
Available from: 2013-05-08 Created: 2013-05-08 Last updated: 2013-06-18Bibliographically approved

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Lizana, Ludvig
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