Roles of Apigenin and Nepetin in the Assembly Behavior and Cytotoxicity of Prion Neuropeptide PrP106-126

Abstract

Development of potential inhibitors to prevent prion protein (PrP) fibrillation is a therapeutic strategy for prion diseases. The prion neuropeptide PrP106-126, a research model of abnormal PrP (PrP Sc ), presents similar physicochemical and biochemical characters to PrP Sc , which is also a target of potential inhibitors against prion deposition. Many flavones have antioxidant, anti-inflammatory, and antibacterial properties, and they are applied in treating prion disorder and other amyloidosis as well. However, the inhibition mechanism of flavones on PrP106-126 fibrillation is still unclear. In the current work, apigenin and nepetin were used to suppress the aggregation of PrP106-126 and to alleviate the peptide-induced cytotoxicity. The results showed that apigenin and nepetin impeded the fibril formation of PrP106-126 and depolymerized the preformed fibrils. They were bound to PrP106-126 predominantly by hydrophobic and hydrogen bonding interactions. In addition, both flavones upregulated cell viability and decreased membrane leakage through reducing peptide oligomerization. The differences in inhibition and cell protection between the two small molecules were presumably attributed to the substitution of hydroxyl and methoxy groups in nepetin, which demonstrated the significant structure−function relationship of flavones with prion neuropeptide and the prospect of flavonoids as drug candidates against prion diseases.

Αnti-prion effects of anthocyanins

“…For example, Quercetin, interaction with PrP Sc fibrils renders them vulnerable to protein degradation, leading to de-aggregation [ 123 , 124 ]. Moreover, Apigenin and Nepetin managed to inhibit the fibrillation of the PrP 106-126 peptide and also depolymerize the already formed fibrils [ 125 ]. It is also worth noting that, Oenin and Myrtillin might exert their anti-prion action with a combination of different mechanisms.…”

Anti-Prion Effects of Anthocyanins

“…For example, Quercetin, interaction with PrP Sc fibrils renders them vulnerable to protein degradation, leading to deaggregation [123,124]. Moreover, Apigenin and Nepetin managed to inhibit the fibrillation of the PrP 106-126 peptide and also depolymerize the already formed fibrils [125]. It is also worth noting that, Oenin and Myrtillin might exert their anti-prion action with a combination of different mechanisms.…”