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Vol 54(2020) N 3 p. 412-415; DOI 10.1134/S0026893320030115  J.J. Li1, C.S. Ryou2, D.-H. Kim3* Effects of SGI-1027 on Formation and Elimination of PrPSc in Prion-Infected Cells 1Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju, 61005 Republic of Korea2Department of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 15588 Republic of Korea 3School of Undergraduate Studies, College of Transdisciplinary Studies, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 42988 Republic of Korea *dhkim1@dgist.ac.kr Received - 2019-08-28; Revised - 2019-11-07; Accepted - 2019-11-13 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. prion, PrPSc, epigenetics, DNA methyl transferase, SGI-1027 |
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