Increased levels of oxidative stress markers detected in the brains of mice devoid of prion protein

Although minor abnormalities have been reported in prion protein (PrP) knoc k-out (Prnp(-/-)) mice, the normal physiological function of PrP, the causa tive agent implicated in transmissible spongiform encephalopathies (TSE), r emains unresolved. Since there are increasing correlations between oxidativ e stress and amyloidoses, we decided to investigate whether PrP plays a rol e in oxidative modulation. We found higher levels of oxidative damage to pr oteins and lipids in the brain lysates of Prnp(-/-) as compared to wild-typ e (WT) mice of the same genetic background. These two indicators, protein o xidation and lipid peroxidation, are hallmarks of cellular oxidative damage . Elevated levels of ubiquitin-protein conjugates were also observed in Prn p(-/-) mice, a probable consequence of cellular attempts to remove the dama ged proteins as indicated by increased proteasome activity. Taken together, these findings are indicative of a role for PrP in oxidative homeostasis i n vivo.