The elucidation of molecular pathological condition in prion disease: analysis of interferon system to develop novel therapeutic method

• Project/Area Number: 16K07042
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Nagasaki University
• Principal Investigator: ISHIBASHI Daisuke 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (10432973)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: プリオン / 自然免疫 / インターフェロン / I型インターフェロン受容体 / IRF3 / 脳神経疾患

Outline of Final Research Achievements

In this study, we investigated a relationship of between type I interferon in innate immune responses and prion infection to host. As a result, we defined that innate immune system mediating type I interferon receptor might negatively regulate prion invasion to host. In the future, we believe that our project will be promoted development of prevention and drug for prion disease.

Academic Significance and Societal Importance of the Research Achievements

これまで注目されてこなかった自然免疫機構を視点としたプリオン感染病態メカニズムの解明について研究を遂行することにより、治療法がないプリオン病の創薬開発が進むことが期待される。

Research Products

• [Journal Article] Prion-Like Seeding of Misfolded α-Synuclein in the Brains of Dementia with Lewy Body Patients in RT-QUIC (2017)
  • Author(s): Sano Kazunori、Atarashi Ryuichiro、Satoh Katsuya、Ishibashi Daisuke、Nakagaki Takehiro、Iwasaki Yasushi、Yoshida Mari、Murayama Shigeo、Mishima Kenichi、Nishida Noriyuki
  • Journal Title: Molecular Neurobiology Volume: - Issue: 5 Pages: 3916-3930
  • DOI: 10.1007/s12035-017-0624-1
  • Peer Reviewed / Open Access
• [Journal Article] Structure-based drug discovery for combating influenza virus by targeting the PA?PB1 interaction (2017)
  • Author(s): Watanabe Ken、Ishikawa Takeshi、Otaki Hiroki、Mizuta Satoshi、Hamada Tsuyoshi、Nakagaki Takehiro、Ishibashi Daisuke、Urata Shuzo、Yasuda Jiro、Tanaka Yoshimasa、Nishida Noriyuki
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 9500-9500
  • DOI: 10.1038/s41598-017-10021-w
  • NAID: 120006987424
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A direct assessment of human prion adhered to steel wire using real-time quaking-induced conversion. (2016)
  • Author(s): Mori T, Atarashi R, Furukawa K, Takatsuki H, Satoh K, Sano K, Nakagaki T, Ishibashi D, Ichimiya K, Hamada M, Nakayama T, Nishida N.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 24993-24993
  • DOI: 10.1038/srep24993
  • Peer Reviewed / Open Access
• [Journal Article] Structure-Based Drug Discovery for Prion Disease Using a Novel Binding Simulation. (2016)
  • Author(s): Ishibashi D, Nakagaki T, Ishikawa T, Atarashi R, Watanabe K, Cruz FA, Hamada T, Nishida N.
  • Journal Title: EBioMedicine. Volume: 9 Pages: 238-249
  • DOI: 10.1016/j.ebiom.2016.06.010
  • NAID: 120006987627
  • Peer Reviewed / Open Access
• [Presentation] プリオン病におけるインシリコ創薬開発 (2018)
  • Author(s): 石橋大輔
  • Organizer: 第８回認知症研究を知る若手研究者の集まり2018
• [Presentation] in silicoプリオン病創薬における薬効特異性の評価 (2018)
  • Author(s): 石橋大輔、中垣岳大、石川岳志、水田賢志、濱田剛、西田教行
  • Organizer: 生体機能と創薬シンポジウム２０１８
• [Presentation] インフルエンザウイルス複製を標的とした蛋白質－蛋白質相互作用阻害剤の開発 (2018)
  • Author(s): 渡邊健, Juliann Nzembi Makau, 石川岳志, 大滝大樹, 水田賢志, 中垣岳大, 石橋大輔, 浦田秀造, 安田二朗, 西田教行
  • Organizer: 第７１回 日本細菌学会九州支部総会・第５５回 日本ウイルス学会九州支部総会
• [Presentation] 炭酸水素カルシウムメゾ構造体によるプリオン不活性化能の検討 (2018)
  • Author(s): 中垣岳大, 的場苑子, 石橋大輔, 西田教行
  • Organizer: 第７１回 日本細菌学会九州支部総会・第５５回 日本ウイルス学会九州支部総会
• [Presentation] I型インターフェロンのプリオン感染に対する抑制作用 Type I interferon suppresses prion infection (2018)
  • Author(s): 石橋大輔, 中垣岳大, 西田教行
  • Organizer: 第91回日本生化学会大会
• [Presentation] Prion-like propagation of filamentous tau inclusions in cultured neuronal cells (2018)
  • Author(s): Gen Matsumoto, Naruhiko Sahara, Daisuke Ishibashi, Noriyuki Nishida, Nozomu Mori
  • Organizer: Asian pacific prion symposium 2018 (APPS2018)
  • Int'l Joint Research
• [Presentation] プリオン感染における自然免疫機構の役割 Protective role of host innate immunity system in prion pathogenesis (2018)
  • Author(s): Daisuke Ishibashi, Takujiro Homma, Takehiro Nakagaki, Kazunori Sano, Kenya Honda, Ryuichiro Atarashi, Noriyuki Nishida
  • Organizer: 日本薬学会第138年会
  • Invited
• [Presentation] プリオン病におけるインシリコ創薬開発 (2017)
  • Author(s): 石橋大輔、石川岳志、中垣岳大、丹下寛也、西田教行
  • Organizer: 第70回日本細菌学会九州支部総会、第54回日本ウイルス学会九州支部総会
• [Presentation] Evaluation of drug specificity for anti-prion compounds selective by structure-based binding simulation in silico プリオン病創薬における薬効特異性の評価 (2017)
  • Author(s): Daisuke Ishibashi, Takehiro Nakagaki, Takeshi Ishikawa, Tsuyoshi Hamada, Noriyuki Nishida
  • Organizer: 2017年度生命科学系学会合同年次大会 (ConBio2017), 第40回日本分子生物学会年会, 第90回日本生化学会大会
• [Presentation] Wire-QuIC reaction can detect abnormal human prion seeds from contaminated stainless steel-wire. Wire-QuICはステンレススチールワイヤー上に付着したプリオンを検出できる (2016)
  • Author(s): Tsuyoshi Mori, Ryuichiro Atarashi, Katsuya Satoh, Daisuke Ishibashi, Takehiro Nakagaki, Noriyuki Nishida
  • Organizer: 第64回日本ウイルス学会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-10-23
• [Presentation] Structure-based drug discovery for prion disease by using a novel binding simulation on the graphics processing unit intensive supercomputer (2016)
  • Author(s): Daisuke Ishibashi, Takehiro Nakagaki, Takeshi Ishikawa, Ryuichiro Atarashi, Tsuyoshi Hamada, Noriyuki Nishida
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-09-25
• [Presentation] Prion strain-dependent effect of macroautophagy on abnormal prion protein degradation (2016)
  • Author(s): Daisuke Ishibashi, Takehiro Nakagaki, Ryuichiro Atarashi, Noriyuki Nishida
  • Organizer: Prion2016 & APPS2016
  • Place of Presentation: 日本教育会館・一橋ホール（東京都・千代田区）
  • Year and Date: 2016-05-10
  • Int'l Joint Research
• [Presentation] Wire-QuIC: A new detection system of human prion (2016)
  • Author(s): Tsuyoshi Mori, Ryuichiro Atarashi, Hanae Takatsuki, Katsuya Satoh, Takehiro Nakagaki, Daisuke Ishibashi, Noriyuki Nishida
  • Organizer: Prion2016 & APPS2016
  • Place of Presentation: 日本教育会館・一橋ホール（東京都・千代田区）
  • Year and Date: 2016-05-10
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] プリオン病治療薬 (2018)
  • Inventor(s): 石橋大輔、西田教行、水田賢志、石川岳志
  • Industrial Property Rights Holder: 国立大学法人長崎大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-177224
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] プリオン病予防・治療剤 (2016)
  • Inventor(s): 石橋大輔、西田教行、中垣岳大、濱田剛、石川岳志
  • Industrial Property Rights Holder: 石橋大輔、西田教行、中垣岳大、濱田剛、石川岳志
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-170349
  • Filing Date: 2016-08-31