Novel Affinity Screening System of PET Probe for Tau aggregates using Human Brain Tissue Microsection

• Project/Area Number: 24510322
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: YOSHIMI Tatsuya 独立行政法人国立長寿医療研究センター, 治療薬探索研究部, 研究員 (30277256)
• Co-Investigator(Kenkyū-buntansha): OSAMU Takikawa 国立長寿医療研究センター, 治療薬探索研究部, 室長 (70163342)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: イメージング質量分析 / アルツハイマー病 / タウ / 創薬スクリーニング / 薬物動態 / PET化合物 / 神経変性疾患 / ロボットシステム / 認知症 / 診断薬 / タウオパシー / PET / 治療薬

Outline of Final Research Achievements

We have developed a novel screening system for affinity chemical compounds visualizing a pathogenic protein, Tau, aggregates in human brain. This system uses tiny stainless microchips to make a number of small frozen brain sections, and imaging mass spectrometry is used for affinity selection of the chemicals. We have screened several affinity chemical compounds which have high affinity to Tau accumulated brain of Alzheimer's disease patient. The system will be useful on drug screening and kinetics analyses. The result will make a contribution to drug discovery and diagnosis of Alzheimer's disease.

Research Products

• [Journal Article] Expression-level dependent perturbation of cell proteostasis and nuclear morphology by aggregation-prone polyglutamine proteins. (2015)
  • Author(s): Lu, M., Williamson, N., Boschetti, C., Ellis, T., Yoshimi, T., Tunnacliffe, A.
  • Journal Title: Biotechnology & Bioengineering Volume: 112 Issue: 9 Pages: 1-28
  • DOI: 10.1002/bit.25606
  • Peer Reviewed
• [Journal Article] Critique of the use of fluorescence-based reporters in Escherichia coli as a screening tool for the identification of peptide inhibitors of Aβ42 aggregation. (2013)
  • Author(s): Wright O, Zhang L, Liu Y, Yoshimi T, Zheng Y, Tunnacliffe A
  • Journal Title: J Pept Sci Volume: 19(2) Issue: 2 Pages: 74-83
  • DOI: 10.1002/psc.2474
  • Peer Reviewed
• [Journal Article] Detection of vertebrate-type steroid hormones and their converting activities in the neogastropod Thais clavigera (Kuster, 1858) (2012)
  • Author(s): Goto Y, Kajiwara M, Yanagisawa Y, Hirose H, Yoshimi T, Umemura M, Nakano H, Takahashi S, Shida Y, Iguchi T, Takahashi Y, Miura T
  • Journal Title: J Mollus Stud Volume: 78(2) Pages: 197-204
  • Peer Reviewed
• [Presentation] 凍結組織切片のイメージング質量分析による病原蛋白PET診断薬開発システム (2015)
  • Author(s): 滝川修、吉見立也、田中耕一、川畑慎一郎
  • Organizer: メディカルジャパン2015大阪、アカデミックフォーラム A-4
  • Place of Presentation: インテックス大阪
  • Year and Date: 2015-02-04 – 2015-02-06
• [Presentation] イメージング質量分析法によるタウ凝集体PET化合物スクリーニング、イメージング質量分析の最前線：創薬と生命科学への応用 (2014)
  • Author(s): 吉見立也
  • Organizer: 第87回生化学会大会フォーラム4F04
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] Characterization of Amyloid-βDegrading Activity in Human Serum. (2014)
  • Author(s): 三河隆太、吉見立也、奥野海良人、岡田健、高柳亜紀子、滝川修
  • Organizer: 第6回NAGOYAグローバルリトリート
  • Place of Presentation: 東浦
• [Presentation] 脳血管細胞によるAβ産生と脳アミロイド血管症 (2013)
  • Author(s): 三河隆太、奥野海良人、岡田健、高柳亜紀子、吉見立也、滝川修
  • Organizer: 第35回神経組織培養研究会
  • Place of Presentation: 大阪
• [Presentation] Implications of brain microvessel endothelial cell-derived amyloid β peptide in cerebral amyloid angiopathy associated with Alzheimer’s disease. (2013)
  • Author(s): Takikawa O, Mikawa R, Okuno A, Yoshimi T, Okada K, Takayanagi A.
  • Organizer: Alzheimer’s disease Association International Conference (AAIC) 2013
  • Place of Presentation: Boston, USA
• [Presentation] 血管内皮細胞によるAβ産生調節機構：脳アミロイド血管症におけるその病態生理学的意義 (2013)
  • Author(s): 三河隆太、吉見立也、奥野海良人、岡田健、高柳亜紀子、滝川修
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Aβ Production from Reactive Astrocytes Induced by Endogenous Neurotoxin Quinolinic Acid: A New Aspect of Alzheimer’s Disease. (2012)
  • Author(s): Okuno A, Zhang G, Yoshimi T, Mikawa R, Takikawa O
  • Organizer: Alzheimer’s disease Association International Conference (AAIC) 2012
  • Place of Presentation: Vancouver, Canada
• [Presentation] Pathogenic role of IDO in Alzheimer’s disease : Astrocytes but not neurons are responsible for the increase of amyloid β peptide induced by neurotoxin quinolinic acid (2012)
  • Author(s): Okuno A, Yoshimi T, Okada K, Mikawa R, Takayanagi A, Takikawa O
  • Organizer: The 13th ISTRY (International Society for Tryptophan Research) conference
  • Place of Presentation: Sydney, Australia
• [Presentation] 反応性アストロサイトによるアミロイドβペプチド産生機構 (2012)
  • Author(s): 吉見立也、奥野海良人、岡田健、三河隆太、高柳亜紀子、滝川修
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Remarks] ロボットスクリーニングシステム紹介 | ラジオアイソトープ管理室
  • URL: http://www.ncgg.go.jp/department/lrs/robot.html
• [Remarks] 自己紹介 | ラジオアイソトープ管理室
  • URL: http://www.ncgg.go.jp/department/lrs/lead01.html
• [Remarks] 治療薬探索研究部 リード分子探索研究室
  • URL: http://www.ncgg.go.jp/department/tsr/lds/index.html
• [Remarks] リード分子探索研究室 Group 1 (2011/4 ~)自己紹介
  • URL: http://www.ncgg.go.jp/department/tsr/lds/lead01.html
• [Patent(Industrial Property Rights)] 微小生体組織片の作製装置、作製方法、及び化合物のスクリーニング方法 (2014)
  • Inventor(s): 滝川修、吉見立也、田中耕一、川畑慎一郎
  • Industrial Property Rights Holder: 滝川修、吉見立也、田中耕一、川畑慎一郎
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-10-17
• [Patent(Industrial Property Rights)] 化学・物理現象検出方法及びその装置 (2013)
  • Inventor(s): 滝川修、奥野海良人、吉見立也、澤田和明、奥村弘一
  • Industrial Property Rights Holder: 滝川修、奥野海良人、吉見立也、澤田和明、奥村弘一
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-112444
  • Filing Date: 2013-05-29