PrPc binds copper and has antioxidant activity enhancing the survival of cells in culture, suggesting that PrPSc accumulation may lead to an aberrant copper metabolism altering the cellular redox state. This proposal centres on understanding to what extend PrPc expression, and susceptibility to prion can be influenced by oxidative stress. In vitro studies with murine neuroblastoma N2a and Schwann MSC80A cells, and in vivo studies with transgenic mice over expressing either mice, human or bovine PrPc, under normal conditions or after various treatments (irradiation, hypoxia, Cu depletion and Mn feeding, ingestion of phosmet) known to cause oxidative stress, will show if and to what extent these stress situations may enhance PrPc expression and the susceptibility to prion infection. The work will also contribute to the basic understanding of PrP and may give information or cellular tools (new chronically infected non neuronal cell model) that could benefit treatment.
Funding SchemeCSC - Cost-sharing contracts
38706 La Tronche