Cell Culture Models For Studying Prion Propagation And Anti-prion Compounds

Abstract

Chronic wasting disease (CWD) of cervids is the most contagious prion disease. To develop new cell culture models for CWD prions, which endogenously expressing cervid PrPc. We have established skin-derived stem cells from antler tissue of Caribou and a non-transformed fibroblast cell line from Indian Muntjac deer. Immunoblot analysis showed that cell lines express glycosylated PrPc at the outer leaflet of the plasma membrane. Then we infected these cells with CWD prions and studied PrPSc uptake and prion propagation. Novel CWD prion propagating cells will be useful for elucidating the molecular mechanisms underlying the pronounced lateral spread of CWD prions. Moreover, we tested Tamoxifen and AR-12 along with its derivatives are able to induce reduction of PrPSc via the autophagic pathway. Both drugs can be used as therapeutic agents against prion infection. Our study provides potentially neuroprotective drugs which might be beneficial in prion disease.