title: Dual MicroRNA to Cellular Prion Protein Inhibits Propagation of Pathogenic Prion Protein in Cultured Cells.
abstract: Prion diseases are fatal transmissible neurodegenerative disorders affecting humans and various mammals. In spite of intensive efforts, there is no effective cure or treatment for prion diseases. Cellular forms of prion protein (PrPC) is essential for propagation of abnormal isoforms of prion protein (PrPSc) and pathogenesis. The effect of an artificial dual microRNA (DmiR) on PrPCsuppression and resultant inhibition of prion replication was determined using prion-infectible cell cultures: differentiated C2C12 culture and primary mixed neuronal and glial cells culture (MNGC). Processing of DmiR by prion-susceptible myotubes, but not by reserve cells, in differentiated C2C12 culture slowed prion replication, implying an importance of cell type-specific PrPCtargeting. In MNGC, reduction of PrPCwith DmiR was effective for suppressing prion replication. MNGC lentivirally transduced with non-targeting control miRNAs (scrambled) reduced prion replication at a level similar to that with a synthetic analogue of viral RNA, poly I:C. The results suggest that a synergistic combination of the immunostimulatory RNA duplexes (miRNA) and PrPCsilencing with DmiR might augment a therapeutic potential of RNA interference.
authors.affiliation: Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, Canada.|Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, AB, Canada.
authors.forename: Sang-Gyun
authors.initials: SG
authors.lastname: Kang
authors.affiliation: Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, Canada.|Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.
authors.forename: Chiye
authors.initials: C
authors.lastname: Kim
authors.affiliation: Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, Canada.|Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, AB, Canada.
authors.forename: Judd
authors.initials: J
authors.lastname: Aiken
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, BK21 PLUS, Seoul National University, Seoul, 08826, Republic of Korea. yoohs@snu.ac.kr.
authors.forename: Han Sang
authors.initials: HS
authors.lastname: Yoo
authors.affiliation: Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, Canada. debbie.mckenzie@ualberta.ca.|Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada. debbie.mckenzie@ualberta.ca.
authors.forename: Debbie
authors.initials: D
authors.lastname: McKenzie
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D000072002:Prion Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D035683:MicroRNAs; D000072002:Prion Proteins
keywords: Differentiated C2C12 cells; Immune stimulator; Neuronal and glial cells; Prion disease; Therapeutic RNAi