A study on neuroprotection by glia-derived lipoproteins against nerve injury

• Project/Area Number: 15K06781
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Hayashi Hideki 東京薬科大学, 薬学部, 講師 (90508657)
• Research Collaborator: Vance Jean E. アルバータ大学, 医学部, 教授
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 緑内障 / リポタンパク質 / グルタミン酸 / アルファ２マクログロブリン / 神経変性 / 神経保護

Outline of Final Research Achievements

Glaucoma is one of the neurodegenerative disorders and the leading cause of blindness in Japan. In our previous study, apolipoprotein E-containing lipoproteins strongly protect primary cultured retinal ganglion cells from glutamate-induced neurodegeneration. Here, we determined a novel neuroprotective mechanism of apolipoprotein E-containing lipoproteins and defined roles of an inhibitory factor against the protective effect of apolipoprotein E-containing lipoproteins.

Research Products

• [Journal Article] Involvement of GSK-3β Phosphorylation Through PI3-K/Akt in Cerebral Ischemia-Induced Neurogenesis in Rats. (2016)
  • Author(s): Kisoh K., Hayashi H., Itoh T., Asada M, Arai M., Yuan B, Tanonaka K., and Takagi N.
  • Journal Title: Mol Neurobiol Volume: - Issue: 10 Pages: 7917-7927
  • DOI: 10.1007/s12035-016-0290-8
  • Peer Reviewed / Open Access
• [Journal Article] Potential neuroprotective effects of an LSD1 inhibitor in retinal ganglion cells via p38 MAPK-gamma activity (2016)
  • Author(s): T. Tsutsumi, K. Iwao, H. Hayashi, T. Kawaji, T. Inoue, S. Hino, M. Nakao, and H. Tanihara.
  • Journal Title: Invest. Ophthalmol. Vis. Sci. Volume: 57 Issue: 14 Pages: 6461-6473
  • DOI: 10.1167/iovs.16-19494
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Active Bufadienolide Compounds on Human Cancer Cells and CD4+CD25+Foxp3+ Regulatory T Cells in Mitogen-activated Human Peripheral Blood Mononuclear Cells. (2016)
  • Author(s): Yuan B., He J., Kisoh K., Hayashi H., Tanaka S., Si N., Zhao H., Hirano T., Bian B. and Takagi N.
  • Journal Title: Oncology Rep Volume: 36 Issue: 3 Pages: 1377-1384
  • DOI: 10.3892/or.2016.4946
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Endogenous Neuroprotective Molecules and Their Mechanisms in the Central Nervous System (2015)
  • Author(s): Hayashi H. and Takagi N.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 8 Pages: 1104-1108
  • DOI: 10.1248/bpb.b15-00361
  • NAID: 130005090640
  • ISSN: 0918-6158, 1347-5215
  • Acknowledgement Compliant
• [Presentation] ラット緑内障モデルの網膜α2マクログロブリンおよびアポE含有リポタンパク質の変化と視神経保護に関する研究 (2018)
  • Author(s): 向垣内 千早、小島 拓也、林 秀樹、小林 美緒、小出 暉、袁 博、高木 教夫
  • Organizer: 第１３８回日本薬理学会関東部会
• [Presentation] ラット緑内障モデルに対するアポE含有リポタンパク質の視神経保護因子としての働き (2018)
  • Author(s): 林 秀樹、森みすず、袁 博、高木 教夫
  • Organizer: 第１３８回日本薬学会
• [Presentation] 虚血性神経障害時の LRP1 の変化と神経保護の可能性 (2018)
  • Author(s): 山田まりこ、林秀樹、岩谷結衣、鈴木かおり、袁博、高木教夫
  • Organizer: 第１３８回日本薬学会
• [Presentation] 視神経保護におけるアポE含有リポタンパク質とアルファ２-マクログロブリンの働き (2017)
  • Author(s): 林 秀樹、森 みすず、橋爪 達哉、原嶋 美奈、降矢 実穂、森 寛子、袁 博、高木 教夫
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台市
  • Year and Date: 2017-03-24
• [Presentation] 視神経保護におけるアポリポタンパク質E含有リポタンパク質とα2-マクログロブリンの役割 (2017)
  • Author(s): 林 秀樹、森 みすず、橋爪 達哉、原嶋 美奈、降矢 実穂、森 寛子、袁 博、高木 教夫
  • Organizer: 第５９回日本脂質生化学会
• [Presentation] 初代培養大脳皮質神経細胞障害時の LRP1 の変化と LP による神経保護への可能性 (2017)
  • Author(s): 山田 まりこ、佐藤 祥子、結城 もえ、袁 博、林 秀樹、高木 教夫
  • Organizer: 第５９回日本脂質生化学会
• [Presentation] ラット緑内障モデルのリポタンパク質受容体LRP1を介した視神経保護と網膜グリア細胞の働き (2017)
  • Author(s): 林 秀樹、森 みすず、橋爪 達哉、原嶋 美奈、降矢 実穂、森 寛子、袁 博、高木 教夫
  • Organizer: 第１９回応用薬理シンポジウム
• [Presentation] リポタンパク質受容体LRP1を介した視神経保護と網膜グリア細胞の働き (2017)
  • Author(s): 林 秀樹、森 みすず、橋爪 達哉、原嶋 美奈、降矢 実穂、森 寛子、袁 博、高木 教夫
  • Organizer: 第９０回日本生化学会
• [Presentation] 中枢神経細胞障害時の LRP1プロセッシングに関わるタンパク質分解酵素と神経生存 (2017)
  • Author(s): 山田まりこ、林秀樹、井上大輔、岩谷結衣、鈴木かおり、袁博、高木教夫
  • Organizer: 第９０回日本生化学会
• [Presentation] Neuroprotective roles of apo E-containing lipoproteins against optic nerve degeneration (2017)
  • Author(s): Hideki Hayashi
  • Organizer: Bridging Discovery Research with Therapies
  • Int'l Joint Research
• [Presentation] Apolipoprotein E containing lipoproteins prevent optic nerve degeneration with a reduction of alpha 2 macroglobulin secretion from retinal glia (2017)
  • Author(s): Hideki Hayashi, Misuzu Mori, Mina Harashima, Tatsuya Hashizume, Miho Furiya, Hiroko Mori, Bo Yuan, Norio Takagi
  • Organizer: Neuroscience 2017, Society for Neuroscience
  • Int'l Joint Research
• [Presentation] Pathologic Roles of Proteolytic Enzymes Associated with Receptor Processing (2017)
  • Author(s): Mariko Yamada, Hideki Hayashi, Nahoko Matsushima, Meiko Ohata, Bo Yuan, Norio Takagi
  • Organizer: Neuroscience 2017, Society for Neuroscience
  • Int'l Joint Research
• [Presentation] Neuroprotective functions of apolipoprotein E-containing lipoproteins in neurons and glia of retina. (2016)
  • Author(s): H. Hayashi, M. Mori, Y. Ban, B.Yuan, N. Takagi
  • Organizer: Neuroscience 2016, Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Cerebral ischemia-mediated phosphorylation of GSK-3β induced neurogenesis in rats. (2016)
  • Author(s): K. Kisoh, H. Hayashi, M. Asada, T. Ito, M. Arai, B. Yuan, N. Takagi
  • Organizer: Neuroscience 2016, Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] 網膜グリア細胞におけるアポE含有リポタンパク質のα2マクログロブリン発現に及ぼす影響 (2016)
  • Author(s): 森みすず、林秀樹、小沢由、上野栞、伊藤玲奈、坂祐樹、袁博、高木教夫
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-26
• [Presentation] Antitumor activity of arsenite and tetrandrine, each alone and in combination, against breast cancer cell line MDA-MB-231 in vitro and in vivo. (2016)
  • Author(s): Wang X., Yao M., Yuan B., Hayashi H. and Takagi N.
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-26
• [Presentation] 網膜の神経変性に対するアポE含有リポタンパク質の神経保護効果 (2016)
  • Author(s): 林秀樹、森みすず、伊藤玲奈、小沢由、上野栞、坂祐樹、袁博、高木教夫
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-09
• [Presentation] マイクロスフェア誘発脳塞栓後の神経新生におけるGSK-3β情報伝達系の関与 (2016)
  • Author(s): 喜早慧士、林秀樹、浅田眞由美、伊藤剛志、新井美穂、袁博、田野中浩一、高木教夫
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-09
• [Presentation] Enhanced antitumor effect of the combination of arsenite with tetrandorine in breast cancer. (2015)
  • Author(s): Yao M., Wang X., Yuan B., Sato A., Sakuma K, Kaneko K., Hayashi H., Toyoda H. and Takagi N.
  • Organizer: 第88回日本生化学会大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] Delphindin induces cytotoxicity and potentiates cytocidal effect in combination with arsenite in an acute promyelocytic leukemia cell line, NB4. (2015)
  • Author(s): Yuan B., Okusumi S., Yoshino Y., Tanaka S., Hirano T., Toyoda H., Hayashi H. and Takagi N.
  • Organizer: 14th Meeting of Consortium for Globalization of Chinese Medicine
  • Place of Presentation: Ontario (Canada)
  • Year and Date: 2015-08-18
  • Int'l Joint Research
• [Remarks] 東京薬科大学薬学部応用生化学教室ホームページ
  • URL: https://www.ps.toyaku.ac.jp/ouyoseika/
• [Remarks] 東京薬科大学薬学部応用生化学教室
  • URL: http://www.ps.toyaku.ac.jp/wp/ouyoseika/