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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
- Molecular Biology, 54(3), 412-415
- Article Type
- Author Keywords
- prion; PrPSc; epigenetics; DNA methyl transferase; SGI-1027
- DISEASES; INHIBITORS
- Recently, SGI-1027, a well-known inhibitor of DNA-methyl transferases (DNMTs), was reported to effectively reduce formation of pathogenic PrPSc in prion-infected cells. Herein, we confirm the elimination of PrPSc 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 PrPSc propagation, SGI-1027 did. Our study suggest that the anti-prion effects of SGI-1027 are a result of its direct interaction with PrPC, which effectively interferes with the pathogenic conformational change of PrPC to PrPSc. We conclude that SGI-1027 driven suppression of pathogenic PrPSc is independent of DNMT. © 2020, Pleiades Publishing, Inc.
- Maik Nauka/Interperiodica Publishing
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- ETC1. Journal Articles
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