Effects of SGI-1027 on Formation and Elimination of PrPSc in Prion-Infected Cells

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...

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Bibliographic Details
Published in:Molecular biology (New York) 2020, Vol.54 (3), p.412-415
Main Authors: Li, J. J., Ryou, C. S., Kim, D.-H.
Format: Article
Language:English
Subjects:
Azacytidine
Biochemistry
Biomedical and Life Sciences
Cell culture
Chronic wasting disease
Human Genetics
Life Sciences
Methionine
Molecular Cell Biology
Prion protein
Propagation
Transmissible spongiform encephalopathy
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Summary: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.
ISSN:0026-8933
1608-3245
DOI:10.1134/S0026893320030115