Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Nikolaos Bekas
Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Eirini Kanata
Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Athanasia Chatziefsthathiou
Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Spyros Pettas
Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece; Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Korina Karagianni
Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Susana Margarida Da Silva Correia
Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University Medicine Goettingen, 37075, Goettingen, Germany
Matthias Schmitz
Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University Medicine Goettingen, 37075, Goettingen, Germany
Inga Zerr
Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University Medicine Goettingen, 37075, Goettingen, Germany
Ioannis Tsamesidis
Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Konstantinos Xanthopoulos
Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Dimitra Dafou
Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece; Corresponding author.
Theodoros Sklaviadis
Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Prion diseases, also known as Transmissible Spongiform Encephalopathies (TSEs), are protein-based neurodegenerative disorders (NDs) affecting humans and animals. They are characterized by the conformational conversion of the normal cellular prion protein, PrPC, into the pathogenic isoform, PrPSc. Prion diseases are invariably fatal and despite ongoing research, no effective prophylactic or therapeutic avenues are currently available. Anthocyanins (ACNs) are unique flavonoid compounds and interest in their use as potential neuroprotective and/or therapeutic agents against NDs, has increased significantly in recent years. Therefore, we investigated the potential anti-oxidant and anti-prion effects of Oenin and Myrtillin, two of the most common anthocyanins, using the most accepted in the field overexpressing PrPSc in vitro model and a cell free protein aggregation model. Our results, indicate both anthocyanins as strong anti-oxidant compounds, upregulating the expression of genes involved in the anti-oxidant response, and reducing the levels of Reactive Oxygen Species (ROS), produced due to pathogenic prion infection, through the activation of the Keap1-Nrf2 pathway. Importantly, they showcased remarkable anti-prion potential, as they not only caused the clearance of pathogenic PrPSc aggregates, but also completely inhibited the formation of PrPSc fibrils in the Cerebrospinal Fluid (CSF) of patients with Creutzfeldt–Jakob disease (CJD). Therefore, Oenin and Myrtillin possess pleiotropic effects, suggesting their potential use as promising preventive and/or therapeutic agents in prion diseases and possibly in the spectrum of neurodegenerative proteinopathies.