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Updated: May 13, 2026

Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase
Published on: June 24, 2025
Quality control system response to stochastic growth of amyloid fibrils
Simone Pigolotti1, Ludvig Lizana, Daniel Otzen
1Dept. de Fisica i Eng. Nuclear, Universitat Politecnica de Catalunya Edif. GAIA, Rambla Sant Nebridi s/n, 08222 Terrassa, Barcelona, Spain. simone.pigolotti@upc.edu
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.
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