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Dynamics of Prion Proliferation Under Combined Treatment of Pharmacological Chaperones and Interferons

Abstract:


Diseases such as mad cow disease in bovines, chronic wasting disease in cervids, and Creutzfeldt-Jakob disease in humans are incurable illnesses caused by prions. Prion diseases are caused when the prion protein PrPC misfolds into PrPSc, which is capable of inducing further misfolding in healthy PrPC proteins. Recent in vivo experimental results have shown that pharmacological chaperone treatment can be used to prevent this conversion, where the pharmacological chaperones act as a short-term “vaccine" against the PrPSc proteins. A second strategic approach uses interferons to decrease the concentration of PrPSc. In this work, a model using a non-linear system of ordinary di-erential equations is constructed to model how these two treatments slow the proliferation of prions in the brain. Through this work it was found that interferons have a greater e˙ect on the prion population over time, but that the pharmacological chaperones begin to e˙ect the system earlier. This information can guide future prion experiments and inform potential treatment protocols.

 

Year: 2019

Authors

Yair Castillo - University of Colima

Nora Culik - Vassar College

Leah Darwin - Arizona State University

Domenica Garzon - Yachay Tech University

Abigail Hardin - University of Oklahoma

Anji Yang - University of Shanghai

Gabriela Navas - Arizona State University 

Aditi Ghosh - University of Wisconsin

Carlos Castillo-Garsow - Eastern Washington University 

Leon Arriola - University of Wisconsin

Karen Rios-Soto - University of Puerto Rico 

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