Structural hormesis in protein aggregation: A minimal mechanistic model
Mallela, A.; Schnell, S.
Show abstract
Protein aggregation underlies the pathogenesis of many neurodegenerative diseases, and inhibitors are often assumed to elicit monotonic dose-responses. We ask whether simple aggregation pathways can intrinsically generate hormesis--a biphasic profile with low-dose stimulation and high-dose inhibition. We formulate a minimal mechanistic model in which a single inhibitor interacts sequentially with pathway intermediates. Analysis and simulation show a robust non-monotonic response: low inhibitor doses increase aggregate formation, whereas high doses suppress it. We prove that this profile is structural--arising from chemical network topology rather than tuned kinetic parameters. The mechanism rationalizes pro-aggregating effects at low doses and underscores the need for full-range dose-response evaluation in inhibitor screening.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Spatial exclusion leads to tug-of-war ecological dynamics between competing species within microchannels 96%
- Stochastic Gene Expression in Proliferating Cells: Differing Noise Intensity in Single-Cell and Population Perspectives 96%
- Dynamic bistable switches enhance robustness and accuracy of cell cycle transitions 96%
Similar papers in this journal
Similar papers in this journal
- Energy-harnessing problem solving of primordial life: modeling the emergence of catalytic host-parasite life cycles 94%
- An amplified derepression controller with multisite inhibition and positive feedback 94%
- SARS-CoV-2 infection dynamics in Denmark, February through October 2020: Nature of the past epidemic and how it may develop in the future 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.