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Novel function of DNMT inhibitors to suppress prions
- Novel function of DNMT inhibitors to suppress prions
- Kim, Dae-Hwan; Ren Chunyan; Ryou Chongsuk; Li Jiaojie
- Issue Date
- 2018년 대한바이러스학회 연구회연합 정기학술대회
- Currently, various therapeutic chemical compounds for prion disease focus on inhibiting to change conformation structure of prion protein. Here, we found that SGI-1027 and SGI-1027 meta/meta analogue (M/M) known as inhibitors for DNA methyltransferases (DNMTs), eliminated PrPSc in prion infected cells. Unlike function of inhibitor for DNMT proteins, effect of SGI-1027 to eliminate PrPSc was more efficient than M/M. In mechanism study, both SGI-1027 and M/M directly interacted with recombinant human truncated PrPC (ht-PrPC) and oligomeric fibril formation from PrPC was inhibited by presence of both compounds. However, PrP gene expression was not repressed under SGI-1027 or M/M. Thus, direct interaction of both compounds with PrPC resulted in elimination of PrPSc in prion infected cells via increasing stability of PrPC structure but not epigenetic control of both compounds such as reduction of PrP gene expression. Also, inhibitory function of SGI-1027 for formation of PrPSc was feasible for protection of cell from prion infection by RML derived pathogenic prion. Along our results, the novel anti-prion function of SGI-1027 and M/M via direct interaction with PrPC can be considered as therapeutic reagents for prion disease.
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- ETC2. Conference Papers
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