Structural hormesis in protein aggregation: A minimal mechanistic model

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.