Optimal control strategies for inhibition of protein aggregation

Significance A range of medical conditions, such as Alzheimer’s disease, Parkinson’s disease, and type II diabetes, are linked to protein aggregation. Thus, it is imperative to develop effective therapeutic strategies to combat protein aggregation. Here, we lay out a general approach for optimizing inhibition strategies based on small molecules that suppress nucleation or growth of aggregates. Our model reveals that the optimal timing of drug administration crucially depends on whether the compound inhibits primary nucleation, secondary nucleation, or the growth of aggregates. This approach could guide the rational design of therapeutic strategies to target protein aggregation diseases.