Neuroprotection via lipoprotein receptors against optic neuropathy

• Project/Area Number: 24500441
• 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 (2013-2014); Kumamoto University (2012)
• Principal Investigator: HIDEKI Hayashi 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): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: リポ蛋白 / 緑内障 / グルタミン酸 / 神経科学 / 脂質 / リポタンパク / 神経保護

Outline of Final Research Achievements

The leading cause of blindness in Japan is glaucoma, which is one of neurodegenerative disorders. We have previously demonstrated that apolipoprotein E-containing lipoproteins strongly protect primary cultured retinal ganglion cells from trophic factors-withdrawal-induced neurodegeneration. In this study, we showed a neuroprotective mechanism of apolipoprotein E-containing lipoproteins via the lipoprotein receptor against glutamate-induced neurotoxicity. We believe that the results of this study provide a novel therapeutic approach for glaucoma.

Research Products

• [Journal Article] Increasing Cellular Level of Phosphatidic Acid Enhances FGF-1 Production in Long Term-cultured Rat Astrocytes (2014)
  • Author(s): Yuko Nagayasu, Shin-ya Morita, Hideki Hayashi, Yutaka Miura, Kazuki Yokoyama, Makoto Michikawa, Jin-ichi Ito
  • Journal Title: Brain Research Volume: 1563 Pages: 31-40
  • DOI: 10.1016/j.brainres.2014.03.035
  • Peer Reviewed
• [Journal Article] Enhancement of FGF-1 release along with cytosolic proteins from rat astrocytes by hydrogen peroxide. (2013)
  • Author(s): Ito, J., Nagayasu, Y., Hoshikawa, M., Kato, K.H., Miura, Y., Asai, K., Hayashi, H., Yokoyama, S., and Michikawa, M
  • Journal Title: Brain Res Volume: 1522 Pages: 12-21
  • Peer Reviewed
• [Journal Article] A potential neuroprotective role of apolipoprotein E-containing lipoproteins through low density lipoprotein receptor-related protein 1 in normal tension glaucoma (2012)
  • Author(s): Hayashi H, Eguchi Y, Fukuchi-Nakaishi Y, Takeya M, Nakagata N, Tanaka K, Vance JE, Tanihara H
  • Journal Title: J Biol Chem Volume: 287(30) Issue: 30 Pages: 25395-406
  • DOI: 10.1074/jbc.m112.370130
  • Peer Reviewed
• [Presentation] アポE含有リポプロテインによる神経保護とその妨害因子の働き (2015)
  • Author(s): 林 秀樹，伊藤 玲奈，上野 栞，袁 博，高木 教夫
  • Organizer: 日本薬学会 第135年会
  • Place of Presentation: 神戸学院大学（神戸）
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Involvement of histone H3 phosphorylation through p38 MAPK pathway activation in casticin-induced cytocidal effects against the human promyelocytic cell line HL-60 (2015)
  • Author(s): B. Yuan, H. Kikuchi, H. Hayashi, H. Toyoda and N. Takagi
  • Organizer: 日本薬学会 第135年会
  • Place of Presentation: 神戸学院大学（神戸）
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Contribution of Akt/MAPK signaling pathways and inhibition of metalloproteinase-2 and 9 expression to gamabufotalin-induced cytotoxicity in human glioblastoma cell line U-87 (2015)
  • Author(s): J. He, B. Yuan, H. Hayashi, B. Bian, and N. Takagi
  • Organizer: 日本薬学会 第135年会
  • Place of Presentation: 神戸学院大学（神戸）
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] グリア細胞由来LRP1リガンドの神経保護における役割 (2015)
  • Author(s): 林 秀樹，小沢 由，袁 博，高木 教夫
  • Organizer: 第88回 日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] ラット脳塞栓後神経新生におけるGSK-3β情報伝達系の関与 (2015)
  • Author(s): 喜早 慧士，林 秀樹，袁 博，田野中 浩一，高木 教夫
  • Organizer: 第88回 日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] グルタミン酸誘発神経障害に対するアポE含有リポプロテインとalpha２-マクログロブリンの神経保護におけるバランス (2014)
  • Author(s): 林 秀樹，袁 博，高木 教夫
  • Organizer: 第87回 日本生化学会大会
  • Place of Presentation: 京都国際会館（京都）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 乳がん細胞MCF-7におけるAsIIIとテトランドリンの併用による殺細胞の増強効果 (2014)
  • Author(s): B. Yuan, A. Sato, K. Sakuma, K. Kaneko, H. Hayashi, H. Toyoda, and N. Takagi
  • Organizer: 第87回 日本生化学会大会
  • Place of Presentation: 京都国際会館（京都）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Cytocidal effects of bufadienolides against human glioblastoma and pancreatic cancer cell lines (2014)
  • Author(s): J. He, B. Yuan, H. Hayashi, B. Bian, and N. Takagi
  • Organizer: 第58回 日本薬学会関東支部大会
  • Place of Presentation: 昭和薬科大学（東京）
  • Year and Date: 2014-10-04
• [Presentation] ラット脳塞栓後の神経新生に及ぼすGSK－3β情報伝達系の関与 (2014)
  • Author(s): 喜早 慧士，丸ノ内 徹郎，林 秀樹，袁 博，田野中 浩一，高木 教夫
  • Organizer: 第58回 日本薬学会関東支部大会
  • Place of Presentation: 昭和薬科大学（東京）
  • Year and Date: 2014-10-04
• [Presentation] アポE含有リポタンパク質とalpha２-マクログロブリンの神経保護効果における役割 (2014)
  • Author(s): 林 秀樹，袁 博，高木 教夫
  • Organizer: 第36回日本生物学的精神医学会 第57回日本神経化学会大会合同年会
  • Place of Presentation: 奈良文化会館（奈良）
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] Mechanisms of casticin-induced cytocidal effects against the human promyelocytic cell line HL-60 (2014)
  • Author(s): B. Yuan, H. Kikuchi, E. Yuhara, H. Hayashi, N. Takagi, and H. Toyoda
  • Organizer: 13th Meeting of Consortium for Globalization of Chinese Medicine (CGCM)
  • Place of Presentation: Beijing (China)
  • Year and Date: 2014-08-27 – 2014-08-29
• [Presentation] Protective effects of high-density lipoproteins against glutamate-induced neurotoxicity in retinal ganglion cells (2014)
  • Author(s): H. Hayashi,and N. Takagi
  • Organizer: 2nd Asian International Symposium of Traditional Medicines
  • Place of Presentation: Tokyo University of Pharmacy and Life Sciences (Hachioji)
  • Year and Date: 2014-05-10
  • Invited
• [Presentation] A protective role of apolipoprotein E-containing lipoproteins in glutamate-induced neurodegeneration. (2013)
  • Author(s): Hayashi H
  • Organizer: The Target Meeting’s 2nd World Neuroscience Online Conference
  • Place of Presentation: Online
  • Invited
• [Presentation] グリア細胞由来アポリポ蛋白E含有リポ蛋白による神経細胞死の制御機構 (2013)
  • Author(s): 林 秀樹
  • Organizer: 第８４回日本動物学会岡山大会
  • Place of Presentation: 岡山
  • Invited
• [Presentation] アポE含有リポプロテインのグルタミン酸誘発神経細胞死に対する保護機構 (2013)
  • Author(s): 林 秀樹
  • Organizer: 第８６回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Neuroprotection by apolipoprotein E-containing lipoproteins against glaucomatous optic neuropathy. (2013)
  • Author(s): 林 秀樹
  • Organizer: 第８６回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] A potential therapeutic role of apolipoprotein E-containing lipoproteins in glaucomatous optic neuropathy. (2012)
  • Author(s): Hayashi H.
  • Organizer: Frontiers in Lipid Biology
  • Place of Presentation: バンフセンター、（バンフ）カナダ
• [Presentation] Neuroprotection by apolipoprotein E-containing lipoproteins via a low density lipoprotein receptor-related protein-1 against glutamate-induced degeneration in vitro and in vivo. (2012)
  • Author(s): Hayashi H.
  • Organizer: 11th Biennial Meeting of the Asian Pacific Society for Neurochemistry
  • Place of Presentation: 神戸国際会議場（神戸）
• [Presentation] アポリポプロテインE含有リポプロテインのグルタミン酸神経障害に対する保護作用 (2012)
  • Author(s): 林 秀樹
  • Organizer: 第５４回日本脂質生化学会
  • Place of Presentation: 九州大学（福岡）
• [Book] Neuroprotection and neurodegeneration for retinal diseases (2014)
  • Author(s): H. Hayashi, edited by T. Nakazawa, Y. Kitaoka, and T. Harada
  • Publisher: Springer
• [Book] Neuroglia Third Edition (2012)
  • Author(s): Kettenmann H., Ransom B.R., Hayashi H. (Chapter 23)
  • Publisher: Oxford University Press
• [Remarks] 東京薬科大学応用生化学教室ホームページ
  • URL: http://www.ps.toyaku.ac.jp/wp/ouyoseika/
• [Remarks] 熊本大学大学院先導機構
  • URL: http://www.kumamoto-u.ac.jp/organizations/sendou
• [Patent(Industrial Property Rights)] リポ蛋白を用いたα２－マクログロブリンの神経保護抑制効果抑止剤及び眼科用組成物 (2014)
  • Inventor(s): 林 秀樹
  • Industrial Property Rights Holder: 林 秀樹
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-534722
  • Filing Date: 2014-03-18
• [Patent(Industrial Property Rights)] リポ蛋白を用いた神経疾患予防・治療剤ならびに神経疾患予防・治療方法 (2012)
  • Inventor(s): 林 秀樹
  • Industrial Property Rights Holder: 熊本大学、東京医科歯科大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-09-19
  • Overseas