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Effects of SGI-1027 on Formation and Elimination of PrP^(Sc) in Prion-Infected Cells

Title
Effects of SGI-1027 on Formation and Elimination of PrP^(Sc) in Prion-Infected Cells
Authors
Li J.J.Ryou C.S.Kim, Dae-Hwan
Issue Date
2020-05
Citation
Molekulyarnaya Biologiya, 54(3), 469-473
Type
Article
Article Type
Article
Author Keywords
DNA methyl transferaseepigeneticsprionPrP^(Sc)SGI-1027
ISSN
0026-8984
Abstract
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.
URI
http://hdl.handle.net/20.500.11750/12038
DOI
10.31857/S0026898420030118
Publisher
Russian Academy of Sciences
Files:
There are no files associated with this item.
Collection:
ETC1. Journal Articles


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