Cellular prion protein offers neuroprotection in astrocytes submitted to amyloid β oligomer toxicity.

The cellular prion protein (PrP), 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 questions about its participation in oxidative and neurodegenerative processes. This study aims to elucidate the involvement of PrP in the neuroprotection cascade in the presence of oxidative stressors. For that, astrocytes from wild-type mice and knockout to PrP were subjected to the induction of oxidative stress with hydrogen peroxide (HO) and with the toxic oligomer of the amyloid β protein (AβO). We observed that the presence of PrP 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 in metal homeostasis, where the absence of PrP leads to metallic unbalance, culminating in cellular vulnerability to oxidative stress. Increased caspase 3, p-Tau, p53, and Bcl2 may establish a relationship between a PrP and an induced damage condition. Complementarily, it has been shown that PrP prevents the internalization of AβO and promotes its degradation under oxidative stress induction, thus preventing protein aggregation in astrocytes. It was also observed that the presence of PrP can be related to translocating SOD1 to cell nuclei under oxidative stress, probably controlling DNA damage. The results of this study suggest that PrP acts against oxidative stress activating the cellular response and defense by displaying neuroprotection to neurons and ensuring the functionality of astrocytes.