Oxidative damage to nucleic acids in human prion disease

Recently, several studies proposed a physiological role for the cellular prion protein (PrP^c) in defense against oxidative stress. Since the pathogenesis of prion disease necessarily involves a disturbance of PrP^c homeostasis, we hypothesized that such diseases would be associated with concomitant disturbances in oxidative balance. In support of such a notion, in this study we show increased oxidative damage to nucleic acids in affected brains of patients with Creutzfeldt-Jakob disease. These data suggest that damage by free radicals is a likely cause for neurodegeneration in human prion disease, and antioxidants are a potential therapy for these disorders. Further, our data support the hypothesis that loss of the anti-oxidant function of PrP^c plays a key role in the pathogenesis of these disorders.