Elucidation of the epigenetic gene regulation related to the inhibition of prion formation

• Project/Area Number: 24659424
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: DOH-URA Katsumi 東北大学, 医学(系)研究科(研究院), 教授 (00263012)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 神経分子病態学 / プリオン / エピゲノム / 治療学 / 糖質

Outline of Final Research Achievements

To elucidate the action mechanism of a compound that is inhibitory against prion formation for a long term, epigenetic modification of chromosomal DNA was examined in the brain tissue samples from the compound-treated mice and the control mice. Both methylation mapping and histone modification mapping were performed by the chromatin immunoprecipitation and promoter array analyses. In addition, gene expression profiling was performed by DNA array analysis and microRNA array analysis using the same brain tissue samples. All results were analyzed bioinfomatically, and candidate genes were finally extracted.

Research Products

• [Journal Article] Heparinase I-specific disaccharide unit of heparin is a key structure but insufficient for exerting anti-prion activity in prion-infected cells. (2015)
  • Author(s): Teruya K, Wakao M, Sato M, Hamanaka T, Nishizawa K, Funayama Y, Sakasegawa Y, Suda Y, Doh-ura K.
  • Journal Title: BBRC Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] プリオン（異常プリオン蛋白）の伝播 (2015)
  • Author(s): 倉橋 洋史、堂浦 克美．
  • Journal Title: Clinical Neuroscience Volume: 33(3) Pages: 260-264
• [Journal Article] Efficacy and Mechanism of a Glycoside Compound Inhibiting Abnormal Prion Protein Formation in Prion-Infected Cells: Implications of Interferon and Phosphodiesterase 4D-Interacting Protein. (2014)
  • Author(s): Nishizawa K, Oguma A, Kawata M, Sakasegawa Y, Teruya K, Doh-Ura K.
  • Journal Title: J Virol. Volume: 88 Issue: 8 Pages: 4083-4099
  • DOI: 10.1128/jvi.03775-13
  • Peer Reviewed / Open Access
• [Journal Article] Detection of Proteinase K-resistant prion protein(PrPres) in mouse neuroblastoma cells. (2014)
  • Author(s): Kurahashi H, Sakasegawa Y, Doh-ura K.
  • Journal Title: PSSJ Arch Volume: 7
  • Peer Reviewed / Open Access
• [Journal Article] Amyloid-binding compounds and their anti-prion potency. (2013)
  • Author(s): Teruya K1, Doh-ura K.
  • Journal Title: Curr Top Med Chem. Volume: 13(19) Pages: 2522-2532
  • Peer Reviewed
• [Journal Article] Protease-resistant PrP and PrP oligomers in the brain in human prion diseases after intraventricular pentosan polysulfate infusion. (2012)
  • Author(s): Honda H, Sasaki K, Minaki H, Masui K, Suzuki SO, Doh-ura K, Iwaki T.
  • Journal Title: Neuropathology. Volume: 32(2) Pages: 124-132
  • Peer Reviewed
• [Presentation] 抗プリオン化合物の作用機序に関する考察 (2015)
  • Author(s): 堂浦 克美．
  • Organizer: 徳島大学疾患酵素学研究センタープリオンセミナー
  • Place of Presentation: 徳島大学疾患酵素学研究センター（徳島）
  • Year and Date: 2015-02-27
  • Invited
• [Presentation] A platinum compound enhances the protease sensitivity of PrPres in cell lysates. (2014)
  • Author(s): Sakasegawa Y, Doh-ura K.
  • Organizer: Asian Pacific Prion Symposium 2014
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2014-07-06 – 2014-07-07
• [Presentation] TSEプリオンとプリオノイドの違い (2014)
  • Author(s): 堂浦 克美．
  • Organizer: 第55回日本神経病理学会総会学術研究会
  • Place of Presentation: 学術総合センター（東京）
  • Year and Date: 2014-06-07
  • Invited
• [Presentation] Drug discovery for prion diseases: dream and reality. (2013)
  • Author(s): Doh-ura K.
  • Organizer: Asian Pacific Prion Symposium 2013
  • Place of Presentation: Nagasaki
  • Invited
• [Presentation] Glycerol enhances the PrPres production via a PI3K signaling pathway in prion-infected neuroblastoma cells. (2013)
  • Author(s): Sakai E, Sakasegawa Y, Doh-ura K.
  • Organizer: Asian Pacific Prion Symposium 2013
  • Place of Presentation: Nagasaki
• [Presentation] プリオン複製に関わる宿主因子の細胞生物学的および生化学的な探索アプローチ。 (2013)
  • Author(s): 逆瀬川裕二、西澤桂子、堂浦克美.
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Extracellular heat shock protein 90 enhances PrPres production in prion-infected neuroblastoma N2a cells. (2012)
  • Author(s): Sakasegawa Y, Doh-ura K.
  • Organizer: Asian Pacific Prion Symposium 2012
  • Place of Presentation: Yokohama
• [Presentation] Applicational research from yeast prion to mammalian prion with Gpg1 and Rnq1Δ100 that inhibitpropagation of yeast prion. (2012)
  • Author(s): Kurahashi H, Doh-ura K.
  • Organizer: Asian Pacific Prion Symposium 2012
  • Place of Presentation: Yokohama
• [Presentation] Melanin-like substances extracted from insect cuticle reduce the PrPres levels in prion-infected cells. (2012)
  • Author(s): Hamanaka T, Doh-ura K.
  • Organizer: Asian Pacific Prion Symposium 2012
  • Place of Presentation: Yokohama
• [Presentation] Glycerol enhances the protease-resistance prion protein production in prion-infected neuroblastoma cells. (2012)
  • Author(s): Sakai E, Doh-ura K.
  • Organizer: Asian Pacific Prion Symposium 2012
  • Place of Presentation: Yokohama
• [Presentation] Dominant negative inhibition by GPI anchor-less recombinant prion proteins is observed in persistently prion infected N2a cells in a culture medium-dependent manner. (2012)
  • Author(s): Sakasegawa Y, Goto Y, Hachiya N, Kaneko K, Doh-ura K.
  • Organizer: Prion2012
  • Place of Presentation: Amsterdam ( Netherlands )
• [Presentation] ヤコブ病治療研究の現状と課題. (2012)
  • Author(s): 堂浦 克美.
  • Organizer: 第6回 食と医療の安全に関わるプリオン病の市民講座
  • Place of Presentation: 東京
• [Presentation] プリオン病に対する治療法の開発. (2012)
  • Author(s): 坪井 義夫、堂浦 克美.
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京