Peroxiredoxin 6 promotes upregulation of the prion protein (PrP) in neuronal cells of prion-infected mice

Apolipoprotein E and peroxiredoxin 6 (PRDX6) were identified as upregulated proteins in brains of scrapie-infected mice and cultured neuronal cell lines. Downregulation of PrP gene expression using specific siRNA did not result in a decrease of PRDX6 amounts. Interestingly, selective siRNA targeting PRDX6 or overexpression of PRDX6 controlled PrPC and PrPSc protein amounts in neuronal cells.Besides its possible function as a novel marker protein in the diagnosis of TSEs, PDRX6 represents an attractive target molecule in putative pharmacological intervention strategies in the future.Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders, which include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeldt-Jacob disease (CJD) in humans [1]. The molecular hallmark of these disorders is a structural conversion in folding of the normal cellular prion protein (PrPC) into a disease-associated, protease-resistant isoform (PrPSc) [2]. Neuropathological characteristics of these diseases include neuronal loss, vacuolar degeneration, astrogliosis and amyloid plaque formation caused by accumulation of PrPSc[3]. However, the mechanism whereby PrPC？→？PrPSc conversion triggers cellular neurotoxicity and neurodegeneration is not well understood.PrPC is a multifunctional plasma membrane glycosylphosphatidylinositol (GPI)-anchored protein on a wide range of different cell types where it is involved in adhesion, signal transduction, differentiation, survival or stress protection [4-6]. Obviously, neurodegenerative disorders interconnect several cellular signal transduction pathways to cause oxidative stress in the brain, including increased oxidative damage, impaired mitochondrial function, defects of the proteasome system, the presence of aggregated proteins, and many more [7]. There are a number of cellular antioxidant defenses to convert reactive oxygen species (ROS) into unreactive compounds, e.g. superoxide dismutase (SO