Dynamics of Prion Proliferation Under CombinedTreatment of Pharmacological Chaperones andInterferons via a Mathematical Model
Ghosh, A.; N. Garzon, D.; Castillo, Y.; Navas-Zuloaga, M.; Culik, N.; Darwin, L.; Hardin, A.; Yang, A.; Garsow, C. C.; Rios-Soto, K.
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Prion diseases are lethal neurodegenerative disorders such as mad cow disease in bovines, chronic wasting disease in cervids, and Creutzfeldt-Jakob disease in humans. They are caused when the prion protein PrPC misfolds into PrPSc, which is capable of inducing further misfolding in healthy PrPC proteins. Recent in vivo experiments show that pharmacological chaperones can temporarily prevent this conversion by binding to PrPC molecules, and thus constitute a possible treatment. A second strategic approach uses interferons to decrease the concentration of PrPSc. In order to study the quantitative effects of these treatments on prion proliferation, we develop a model using a non-linear system of ordinary differential equations. By evaluating their efficacy and potency, we find that interferons act at lower doses and achieve greater prion decay rates. However, there are benefits in combining them with pharmacological chaperones in a two-fold therapy. This research is crucial to guide future prion experiments and inform potential treatment protocols.Competing Interest StatementThe authors have declared no competing interest.View Full Text
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