Using two-dimensional gel electrophoresis (2-DE) and Western blot analysis, we were able to identify and quantify six antioxidant proteins, peroxiredoxin (Prx) 1 Prx 11 Prx 111,,, 1-Cys Prx, putative peroxisomal antioxidant enzyme (PLP), and mitochondrial Mn superoxide dismutase (Mn-SOD) in two individual brain regions, cerebellum and frontal cortex of patients with sporadic Creutzfeldt-Jacob (sCJD). Among six antioxidant proteins, 1-Cys Prx showed significant increase (P < 0.05) in sCJD frontal cortex whereas Prx I was decreased (P < 0.01). In cerebellum, levels of all antioxidant proteins studied. were comparable to those of controls. Our findings provide evidence for the link between aberrant expression of antioxidant proteins, 1-Cys Prx and Prx I and CJD neuropathogenesis and we discuss the neuropathological meaning of these dysregulated antioxidant proteins in sCJD brain.