Oxidative stress and prion protein

Research project P 14584 Oxidative stress and prion protein Herbert BUDKA 09.10.2000 An abnormal configuration of the prion protein (PrP) has an essential role for disease manifestation in the transmissible spongiform encephalo-pathies (TSEs) or prion diseases. However, the physiological role of the normal prion protein (PrP C) is not clarified. Recent in vitro studies suggest a function of PrP in the cellular defence against oxidative stress. In this project, we try to clarify whether oxidative stress occurs in the neurodegeneration of prion diseases and whether PrP` is indeed involved in oxidative stress defence. First, we shall study, by immunohistochemistry and biochemistry on human and animal TSE cases, the expression of oxidative stress markers during disease development and in the terminal stage. Furthermore, we shall study the expression of PrP C itself via immunohistochemical and biochemical methods in other human and animal neurodegenerative diseases in which oxidative stress has been shown to be an important event. Additionally, we will investigate the level of PrP C expression in cell culture after exposure to free radicals. Elucidation of these pathopysiological and pathogenetic mechanisms should contribute to the -rationale for therapeutic strategies in TSEs.