Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:[Effects of SGI-1027 on Formation and Elimination of PrP^(Sc) in Prion-Infected Cells]. 3249 10