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Quality control system response to stochastic growth of amyloid fibrils
Author(s) -
Pigolotti Simone,
Lizana Ludvig,
Otzen Daniel,
Sneppen Kim
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.03.018
Subject(s) - amyloid fibril , aggregate (composite) , quality (philosophy) , biophysics , biological system , control (management) , protein aggregation , process (computing) , computer science , chemistry , mechanism (biology) , materials science , nanotechnology , amyloid β , biology , physics , biochemistry , artificial intelligence , medicine , disease , pathology , quantum mechanics , operating system
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.