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Effects of SGI-1027 on Formation and Elimination of PrP^(Sc) in Prion-Infected Cells
- Effects of SGI-1027 on Formation and Elimination of PrP^(Sc) in Prion-Infected Cells
- Li J.J.; Ryou C.S.; Kim, Dae-Hwan
- Issue Date
- Molekulyarnaya Biologiya, 54(3), 469-473
- Article Type
- Author Keywords
- DNA methyl transferase; epigenetics; prion; PrP^(Sc); SGI-1027
- Recently, SGI-1027, a well-known inhibitor of DNA-methyl transferases (DNMTs), was reported to effectively reduce formation of pathogenic PrP^(Sc) in prion-infected cells. Herein, we confirm the elimination of PrP^(Sc) in chronic wasting disease (CWD) prion-infected neurons by SGI-1027, and pinpoint the binding region of human prion protein to SGI-1027. SGI-1027 is broadly functional against various prion disease types, including human prions. Previously, the inhibitory effects of SGI-1027 on DNMT function is well tested in various cell culture models. While neither treatment with a DNMTs enhancer S-adenosyl-L-methionine (SAM), nor with their inhibitor, 5-azacytidine, prevented PrP^(Sc) propagation, SGI-1027 did. Our study suggest that the anti-prion effects of SGI-1027 are a result of its direct interaction with PrP^(C), which effectively interferes with the pathogenic conformational change of PrP^(C) to PrP^(Sc). We conclude that SGI-1027 driven suppression of pathogenic PrP^(Sc) is independent of DNMT.
- Russian Academy of Sciences
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- ETC1. Journal Articles
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