Quality control system response to stochastic growth of amyloid fibrils

• We propose a stochastic model describing in vivo protein aggregation.
• We assume that the cell quality control systems actively degrades aggregates.
• We estimate the parameters of the model from experimental knowledge.
• The model predicts oscillations when the quality control system is impaired.
• During oscillations, aggregates of large size can be formed.

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.