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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]

J J Li, C S Ryou, D-H Kim

Mol Biol (Mosk). May-Jun 2020;54(3):469-473.

PMID: 32492010

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1020149738	SGI-1027		1020149-73-8	Price

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