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

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Abstract

The cellular prion protein (PrPC), 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 PrPC in the neuroprotection cascade in the presence of oxidative stressors. For that, astrocytes from wild-type mice and knockout to PrPC were subjected to the induction of oxidative stress with hydrogen peroxide (H2O2) and with the toxic oligomer of the amyloid β protein (AβO). We observed that the presence of PrPC 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 PrPC in metal homeostasis, where the absence of PrPC 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 PrPC and an induced damage condition. Complementarily, it has been shown that PrPC 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 PrPC can be related to translocating SOD1 to cell nuclei under oxidative stress, probably controlling DNA damage. The results of this study suggest that PrPC acts against oxidative stress activating the cellular response and defense by displaying neuroprotection to neurons and ensuring the functionality of astrocytes.

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Acknowledgements

The authors are grateful to the multiuser central facilities (UFABC) for the experimental support. We thank Dr. Vilma R. Martins and Dr. Tiago Góss dos Santos, from AC Camargo (São Paulo, Brazil), for donating anti-PrPC produced in Wild-type mice.

Funding

The authors thank Sao Paulo State Foundation (FAPESP grant 2018/14152–0 and 2020/14175–0), and CNPq (grant 307856/2021-6). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)-Finance Code 001.

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Authors and Affiliations

  1. Center for Natural Sciences and Humanities, Federal University of ABC – UFABC, Avenida dos Estados, 5001, Santo André, SP, 09210-580, Brazil

    Caroline M. S. Marques, Rafael N. Gomes, Tatiana Pedron, Bruno L. Batista & Giselle Cerchiaro

  2. Metal Biochemistry and Oxidative Stress Lab, Center for Natural Sciences and Humanities, Federal University of ABC – UFABC, Avenida dos Estados, 5001, Bloco B, Santo André, SP, 09210-580, Brazil

    Caroline M. S. Marques, Rafael N. Gomes & Giselle Cerchiaro

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  1. Caroline M. S. Marques
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  2. Rafael N. Gomes
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Contributions

CMSM, RNG, TP, BLB, and GC: designed the experiments, performed research, and analyzed the data. GC: conceived the study. CMSM and GC: wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Giselle Cerchiaro.

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Marques, C.M.S., Gomes, R.N., Pedron, T. et al. Cellular prion protein offers neuroprotection in astrocytes submitted to amyloid β oligomer toxicity. Mol Cell Biochem 478, 1847–1865 (2023). https://doi.org/10.1007/s11010-022-04631-w

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