title: A Single Subcutaneous Injection of Cellulose Ethers Administered Long before Infection Confers Sustained Protection against Prion Diseases in Rodents.
abstract: Prion diseases are fatal, progressive, neurodegenerative diseases caused by prion accumulation in the brain and lymphoreticular system. Here we report that a single subcutaneous injection of cellulose ethers (CEs), which are commonly used as inactive ingredients in foods and pharmaceuticals, markedly prolonged the lives of mice and hamsters intracerebrally or intraperitoneally infected with the 263K hamster prion. CEs provided sustained protection even when a single injection was given as long as one year before infection. These effects were linked with persistent residues of CEs in various tissues. More effective CEs had less macrophage uptake ratios and hydrophobic modification of CEs abolished the effectiveness. CEs were significantly effective in other prion disease animal models; however, the effects were less remarkable than those observed in the 263K prion-infected animals. The genetic background of the animal model was suggested to influence the effects of CEs. CEs did not modify prion protein expression but inhibited abnormal prion protein formation in vitro and in prion-infected cells. Although the mechanism of CEs in vivo remains to be solved, these findings suggest that they aid in elucidating disease susceptibility and preventing prion diseases.
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Kenta
authors.identifier: http://orcid.org/0000-0002-0500-986X
authors.initials: K
authors.lastname: Teruya
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Oguma
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nishizawa
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Kawata
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakasegawa
authors.affiliation: Division of Forest and Biomaterials Science, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Hiroshi
authors.identifier: http://orcid.org/0000-0002-0130-1919
authors.initials: H
authors.lastname: Kamitakahara
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Doh-Ura
mesh_terms: D000818:Animals; D002482:Cellulose / Q000494:pharmacology; D006224:Cricetinae; D004195:Disease Models, Animal; D004987:Ethers / Q000494:pharmacology; D065347:Hypromellose Derivatives / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000473:pathology*
chemical_list: D004987:Ethers; D065347:Hypromellose Derivatives; D002482:Cellulose