Cellular prion protein offers neuroprotection in astrocytes under oxidative stress

The cellular prion protein (PrP C ), in its native conformation, performs numerous cellular and cognitive functions in brain tissue. However, despite the cellular prion research in recent years, there are still doubts about its activities and how its molecular interface occurs in oxidative and neurodegenerative processes. Also, its metal-protein interaction is not apparent. This study aims to elucidate the participation of PrP C in the neuroprotection cascade in the presence of oxidative stressors. For that, astrocytes from wild-type mice and knockout to PrP C were subjected to the induction of oxidative stress with hydrogen peroxide (H 2 O 2 ) and with the toxic oligomer of the beta-amyloid protein (Aβo). We observed that the presence of PrP C showed resistance in the cell viability of astrocytes. It was also possible to monitor changes in basic levels of metals and associate them with an induced damage condition, indicating the precise role of PrP C in metal homeostasis, where the absence of PrP C leads to metallic unbalance culminating in cellular vulnerability to oxidative stress. Activation of specific proteins at different levels was also observed, such as caspase 3, Tau, p-Tau, p53, and Bcl2, which may establish a relationship between a PrP C and an induced damage condition. Complementarily, it has been shown that PrP C prevents the internalization of AβO and/or promotes its degradation under oxidative stress induction and thus prevents protein aggregation in astrocytes. It was also observed that the PrP C is responsible for translocating SOD1 to cell nuclei under conditions of oxidative stress, probably controlling DNA damage. The results obtained in this study proved that PrP C acts against oxidative stress, activating the cellular response and defense by displaying neuroprotection to neurons and ensuring the functionality of astrocytes.