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Effects of SGI-1027 on Formation and Elimination of PrP Sc in Prion-Infected Cells
Molecular Biology ( IF 1.2 ) Pub Date : 2020-06-17 , DOI: 10.1134/s0026893320030115 J. J. Li , C. S. Ryou , D.-H. Kim
中文翻译:
SGI-1027对Pri病毒感染细胞中PrP Sc的形成和消除的影响
更新日期:2020-06-17
Molecular Biology ( IF 1.2 ) Pub Date : 2020-06-17 , DOI: 10.1134/s0026893320030115 J. J. Li , C. S. Ryou , D.-H. Kim
Abstract
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.中文翻译:
SGI-1027对Pri病毒感染细胞中PrP Sc的形成和消除的影响