Towards Optimal Control of Amyloid Fibrillation.

ABSTRACT

Epigallocatechin-3-gallate, as a representative amyloid inhibitors, has shown a promising ability against A[Formula see text] fibrillation by directly degradating the mature fibrils. Most previous studies have been focusing on its functional mechanisms, meanwhile its optimal dosage has been seldom considered. To solve this critical issue, we refer to the generalized Logistic model for amyloid fibrillation and inhibition and adopt the optimal control theory to balance the effectiveness and cost (or toxicity) of inhibitors. The optimal control trajectory of inhibitors is analytically solved, based on which the influence of model parameters, the difference between the optimal control strategy and several other traditional drug dosing strategies are systematically compared and validated through experiments. It is found that the strategy of multiple-times adding is more suitable for a long-term disease treatment, while single high-dose therapy is preferred for a short-term treatment. We hope our findings can shed light on the rational usage of amyloid inhibitors in clinic.