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Faculty of Medicine School of Medicine Department of Infectious Diseases, Microbiology |
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Assistant Professor |
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MORI Tsuyoshi
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Degree 【 display / non-display 】
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博士（医学） ( 2007.3 長崎大学 )
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修士（食品栄養科学） ( 2001.3 静岡県立大学 )
Papers 【 display / non-display 】
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Administration of L-Type Bovine Spongiform Encephalopathy to Macaques to Evaluate Zoonotic Potential Reviewed
Imamura M., Hagiwara K., Tobiume M., Ohno M., Iguchi H., Takatsuki H., Mori T., Atarashi R., Shibata H., Ono F.
Emerging Infectious Diseases 31 ( 5 ) 986 - 987 2025.5
Publishing type：Research paper (scientific journal) Publisher：Emerging Infectious Diseases
We administered L-type bovine spongiform encephalopathy prions to macaques to determine their potential for transmission to humans. After 75 months, no clinical symptoms appeared, and prions were undetectable in any tissue by Western blot or immunohistochemistry. Protein misfolding cyclic amplification, however, revealed prions in the nerve and lymphoid tissues.
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Takatsuki H, Imamura M, Mori T, Atarashi R
Sci Rep 12 ( 1 ) 7923 2022.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
Each prion strain has its own characteristics and the efficacy of anti-prion drugs varies. Screening of prion disease therapeutics is typically evaluated by measuring amounts of protease-resistant prion protein (PrP-res). However, it remains unclear whether such measurements correlate with seeding activity, which is evaluated by real-time quaking-induced conversion (RT-QuIC). In this study, the effects of anti-prion compounds pentosan polysulfate (PPS), Congo red, and alprenolol were measured in N2a58 cells infected with Fukuoka-1 (FK1) or 22L strain. The compounds abolished PrP-res and seeding activity, except for N2a58/FK1 treated with PPS. Interestingly, the seeding activity of N2a58/FK1, which was reduced in the presence of PPS, was not lost and remained at low levels. However, upon removal of PPS, both were gradually restored to their original levels. These results indicate that low-level persistent prion infection keeping measurable seeding activity is induced by PPS in a strain-dependent manner. Furthermore, for protein misfolding cyclic amplification (PMCA), the anti-prion effect of PPS decreased in FK1 compared to 22L, suggesting that the differences occur at the level of the direct conversion. Our findings demonstrate that the advantages of RT-QuIC and PMCA can be exploited for more accurate assessment of therapeutic drug screening, reflecting strain differences.
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Imamura M, Tabeta N, Iwamaru Y, Takatsuki H, Mori T, Atarashi R
Biochem Biophys Res Commun 613 67 - 72 2022.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications
Prion diseases are transmissible and progressive neurodegenerative disorders characterized by abnormal prion protein (PrPSc) accumulation in the central nervous system. Generation of synthetic PrPSc in a cell-free conversion system and examination of its transmissibility to animals would facilitate testing of the protein-only hypothesis and the understanding of the molecular basis of sporadic prion diseases. In this study, we used recombinant prion protein from a baculovirus-insect cell expression system (Bac-rPrP) and insect cell-derived cofactors to determine whether Bac-rPrPSc is spontaneously produced in intermittent ultrasonic reactions. No spontaneous generation of Bac-rPrPSc was observed at 37 °C, but when the reaction temperature was increased to 45 °C, Bac-rPrPSc was generated in all trials. Some Bac-rPrPSc variants were transmissible to mice, but when the reaction was repeated for 40 rounds, the transmissibility was lost. Notably, a variety of Bac-rPrPSc variants, including non-transmissible ones, differing in resistance to proteinase K and cofactor dependence during amplification, was generated under the same experimental conditions, including the same sonication settings and cofactors. However, their characteristics also disappeared after 40 reaction rounds and the variety converged onto a single variant. These results indicate that various Bac-rPrPSc variants with different transmissibility to mice and structural properties are generated, which compete with each other and gradually converge onto a variant with a slightly faster amplification rate.
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Ethanolamine is a new anti‐prion compound
Uchiyama K., Hara H., Chida J., Pasiana A.D., Imamura M., Mori T., Takatsuki H., Atarashi R., Sakaguchi S.
International Journal of Molecular Sciences 22 ( 21 ) 2021.11
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：International Journal of Molecular Sciences
Prion diseases are a group of fatal neurodegenerative disorders caused by accumulation of proteinaceous infectious particles, or prions, which mainly consist of the abnormally folded, am-yloidogenic prion protein, designated PrPSc. PrPSc is produced through conformational conversion of the cellular isoform of prion protein, PrPC, in the brain. To date, no effective therapies for prion diseases have been developed. In this study, we incidentally noticed that mouse neuroblastoma N2a cells persistently infected with 22L scrapie prions, termed N2aC24L1‐3 cells, reduced PrPSc levels when cultured in advanced Dulbecco’s modified eagle medium (DMEM) but not in classic DMEM. PrPC levels remained unchanged in prion‐uninfected parent N2aC24 cells cultured in advanced DMEM. These results suggest that advanced DMEM may contain an anti‐prion compound(s). We then successfully identified ethanolamine in advanced DMEM has an anti‐prion activity. Ethanola-mine reduced PrPSc levels in N2aC24L1‐3 cells, but not PrPC levels in N2aC24 cells. Also, oral administration of ethanolamine through drinking water delayed prion disease in mice intracerebrally inoculated with RML scrapie prions. These results suggest that ethanolamine could be a new anti-prion compound.
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Ethanolamine is a new anti-prion compound. Reviewed International coauthorship
Uchiyama K, Hara H, Chida J, Pasiana AD, Imamura M, Mori T, Takatsuki H, Atarashi R, Sakaguchi S
Int J Mol Sci 22 ( 21 ) 11742 2021.10
Language：English Publishing type：Research paper (scientific journal)
MISC 【 display / non-display 】
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バキュロウイルス-昆虫細胞発現組換えPrP を用いた試験管内変換系の構築に基づくプリオン変換・生成機構の解明. Invited
今村守一，森剛志，高月英恵，岩丸祥史，新竜一郎
YAKUGAKU ZASSHI 139 ( 7 ) 989 - 992 2019.7
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal) Publisher：公益財団法人日本薬学会
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シナプスの病態 プリオン病
森 剛志, 坂口末廣
Clinical Neuroscience 28 ( 8 ) 906 - 908 2010.8
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal) Publisher：中外医学社
Presentations 【 display / non-display 】
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ヒトグリオーマ細胞におけるプリオン感染動態の解析.
森剛志, 今村守一, 髙月英恵, 井口洋美, 大野美奈子, 新竜一郎
第68回日本ウイルス学会学術集会 2021.11.16
Event date： 2021.11.16 - 2021.11.18
Language：Japanese Presentation type：Oral presentation (general)
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スクレイピー感染ヒツジ脳には複数のプリオン株が混在している.
今村守一, 宮澤光太郎, 森剛志, 髙月英恵, 新竜一郎
九州微生物研究フォーラム2021 2021.9.11
Event date： 2021.9.10 - 2021.9.11
Language：Japanese Presentation type：Oral presentation (general)
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さまざまなリコンビナントプリオン蛋白を基質としたRT-QUIC法の反応性の比較解析.
森剛志, 今村守一, 高月英恵, 井口洋美, 大野美奈子, 新竜一郎
第67回日本ウイルス学会学術集会 (東京都江戸川区) 日本ウイルス学会
Event date： 2019.10.29 - 2019.10.31
Language：Japanese Presentation type：Poster presentation
Venue：東京都江戸川区
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Isolation of hidden minor prion conformers from classical scrapie isolates in advanced protein misfolding cyclic amplification in the presence of arginine ethyl ester. International conference
Imamura M, Miyazawa K, Matsuura Y, Iwamaru Y, Kitamoto T, Mohri S, Takatsuki H, Mori T, Atarashi R
APPS2019 (Wako, Saitama) Asian Pacific Prion Symposium
Event date： 2019.10.3 - 2019.10.4
Language：English Presentation type：Poster presentation
Venue：Wako, Saitama
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Pentosan polysulfate induces latent prion infection in Fukuoka-1 strain-infected cells. International conference
Takatsuki H, Mori T, Imamura M, Atarashi R
APPS2019 (Wako, Saitama) Asian Pacific Prion Symposium
Event date： 2019.10.3 - 2019.10.4
Language：English Presentation type：Poster presentation
Venue：Wako, Saitama
Grant-in-Aid for Scientific Research 【 display / non-display 】
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脳・脊髄液以外の検体からの微量異常型プリオン蛋白検出法の開発
Grant number：23K06946 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
Authorship：Principal investigator
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採取容易な検体を用いたクロイツフェルト・ヤコブ病早期診断法の確立
Grant number：20K07807 2020.04 - 2023.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
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クロイツフェルト・ヤコブ病のタイプを鑑別可能なコンビネーションQUIC法の構築
Grant number：17K10022 2017.04 - 2020.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
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プリオン高感度検出法を用いたヤコブ病タイプ鑑別診断法の開発とその分子機構の解明
Grant number：26461507 2014.04 - 2017.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator