Αnti-prion effects of anthocyanins

• DOI: 10.1016/j.redox.2024.103133
• Publication Date: 2024-03-28T17:07:39Z
• Authors: Nikoletta Christo...; Nikolaos Bekas; Eirini Kanata; Athanasia Chatzie...; Spyros Pettas; Korina Karagianni; Susana Margarida ...; Matthias Schmitz; Inga Zerr; Ioannis Tsamesidis; Konstantinos Xant...; Dimitra Dafou; Theodoros Sklaviadis
• Keywords: drug effects [Signal Transduction]; Medicine (General); PrPSc Proteins; QH301-705.5; NF-E2-Related Factor 2; metabolism [NF-E2-Related Factor 2]; Anti-oxidant; Antioxidants; Prion Diseases; Anthocyanins; PrP(Sc); R5-920; ddc:570; pharmacology [Antioxidants]; Humans; Animals; metabolism [Reactive Oxygen Species]; chemistry [Anthocyanins]; Biology (General); drug therapy [Prion Diseases]; Kelch-Like ECH-Associated Protein 1; metabolism [Kelch-Like ECH-Associated Protein 1]; pharmacology [Anthocyanins]; KEAP1 protein, human; Neuroprotection; NFE2L2 protein, human; pathology [Prion Diseases]; metabolism [PrPSc Proteins]; Proteinopathies; Prion; Reactive Oxygen Species; metabolism [Prion Diseases]; PrPSc; Research Paper; Signal Transduction

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 PrPScin 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.