A study of molecular mechanisms of endoplasmic reticulum stress in retinal ganglion cell death

• Project/Area Number: 20592082
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: SHIMAZAWA Masamitsu Gifu Pharmaceutical University, 薬学部, 准教授 (80381721)
• Co-Investigator(Kenkyū-buntansha): HARA Hideaki 岐阜薬科大学, 薬学部, 教授 (20381717)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 小胞体ストレス / 網膜神経節細胞 / 緑内障

Research Abstract

We identified a small molecule, SUN N8075 [(2S)-1-(4-amino-2,3,5-trimethylphenoxy)-3-(4-[4-(4-fluorobenzyl)phenyl]-1-piperazinyl)-2-p ropanol dimethanesulfonate], which has a marked protective effect on ER stress-induced cell death, in an in vitro cell-based screening. Its protective mechanism was mediated by an induction of VGF nerve growth factor inducible (VGF). Elucidating the involvements of VGF in retinal diseases will be expected to provide a potential target for therapeutic intervention in retinal diseases in future.

Research Products

• [Journal Article] SUN N8075, anovel radical scavenger, protectsagainst retinal cell death in mice. (2011)
  • Author(s): Akane M., Shimazawa M., Inokuchi Y.,Tsuruma K., Hara H.
  • Journal Title: Neurosci. Lett 488 Pages: 87-91
  • Peer Reviewed
• [Journal Article] Involvement ofendoplasmic reticulum stress onneuronal cell death in the lateralgeniculate nucleus in the monkeyglaucoma model. (2011)
  • Author(s): Ito Y., Shimazawa M., Inokuchi Y.,Yamanaka H., Tsuruma K., Imamura K.,Onoe H., Watanabe Y., Aihara M., AraieM., Hara H.
  • Journal Title: European Journal of Neuroscience 33 Pages: 843-855
• [Journal Article] SUN N8075, a novel radical scavenger, protects against retinal cell death in mice. (2011)
  • Author(s): Masamitsu Shimazawa, Hideaki Hara
  • Journal Title: Neurosci.Lett. Volume: 488 Pages: 87-91
  • Peer Reviewed
• [Journal Article] Involvement of endoplasmic reticulum stress on neuronal cell death in the lateral geniculate nucleus in the monkey glaucoma model (2011)
  • Author(s): Masamitsu Shimazawa, Hideaki Hara
  • Journal Title: European Journal of Neuroscience Volume: 33 Pages: 843-855
  • Peer Reviewed
• [Journal Article] An inducer of VGF protectscells from ER stress-induced celldeath and prolongs survival in the mutant SOD1 animal models of familial ALS. (2010)
  • Author(s): Shimazawa M., Tanaka H., Ito Y.,Morimoto N., Tsuruma K., Kadokura M.,Tamura S., Inoue Y., Yamada M.,Takahashi H., Warita H., Aoki M., Hara H.
  • Journal Title: PLoS ONE, 5
  • Peer Reviewed
• [Journal Article] A novel calpaininhibitor,((1S)-1-((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945),reduces murine retinal cell death invitro and in vivo. (2010)
  • Author(s): Shimazawa M., Suemori S., Inokuchi Y.,Matsunaga N., Nakajima Y., Oka T.,Yamamoto T., Hara H.
  • Journal Title: J. Pharmacol. Exp.Ther 332 Pages: 380-387
  • Peer Reviewed
• [Journal Article] An inducer of VGF protects cells from ER stress-induced cell death and prolongs survival in the mutant SOD1 animal models of familial ALS. (2010)
  • Author(s): Masamitsu Shimazawa, Hideaki Hara
  • Journal Title: PLoS ONE Volume: 5
  • Peer Reviewed
• [Journal Article] A Novel Calpain Inhibitor, ((1S)-1-((((1S)-1-Benzyl-3-cyclopropylamino-2, 3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic Acid 5-Methoxy-3-oxapentyl Ester(SNJ-1945), Reduces Murine Retinal Cell Death in Vitro and in Vivo (2010)
  • Author(s): Masamitsu Shimazawa
  • Journal Title: J.Pharmacol.Exp.Ther 332 Pages: 380-387
  • Peer Reviewed
• [Journal Article] Involvement of Bid and caspase-2 inendoplasmic reticulum stress- andoxidative stress-induced retinalganglion cell death.
  • Author(s): Uchibayashi R., Tsuruma K., Inokuchi Y., Shimazawa M., Hara H.
  • Journal Title: J. Neurosci. Res in press
  • Peer Reviewed
• [Presentation] The effect of SUN N8075 on endoplasmic reticulum stress-induced death in RGC-5 cells (2010)
  • Author(s): Masamitsu Shimazawa
  • Organizer: ARVO2010
  • Place of Presentation: Convention Center (Fort Lauderdale, Florida)
  • Year and Date: 2010-05-06
• [Presentation] The effect of SUN N8075 on endoplasmic reticulumstress-induced cell death in RGC-5 cells. (2010)
  • Author(s): 嶋澤雅光, 内林瑠美, 鶴間一寛, 原英彰
  • Organizer: ARVO 2010 Annual Meeting
  • Place of Presentation: FortLauderdale, Florida
• [Presentation] Involvement ofendoplasmic reticulum stress onneuronal degeneration in the lateralgeniculate nucleus in the monkeyglaucoma model. (2010)
  • Author(s): Ito Y., Shimazawa M., Inokuchi Y., Miwa A., Yamanaka H., Tsuruma K., Onoe H., Araie M., Hara H.
  • Organizer: ARVO 2010 AnnualMeeting
  • Place of Presentation: Fort Lauderdale, Florida
• [Presentation] 網膜神経節細胞死におけるBid およびCaspase 2 の関与 (2009)
  • Author(s): 内林瑠美、井口勇太、嶋澤雅光、鶴間一寛、原英彰
  • Organizer: 第116 回日本薬理学会近畿部会
  • Place of Presentation: 大津
  • Year and Date: 2009-11-13
• [Presentation] 網膜神経節細胞死における Bid および Caspase 2の関与 (2009)
  • Author(s): 内林瑠美
  • Organizer: 第116回日本薬理学会近畿部会
  • Place of Presentation: ピアザ淡海(大津市)
  • Year and Date: 2009-11-13
• [Presentation] 網膜神経節細胞死に対するSUN N8075の保護作用 (2009)
  • Author(s): 内林 瑠美
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: パシフイコ横浜
  • Year and Date: 2009-03-17
• [Presentation] 網膜神経節細胞死に対する SUN N8075 の保護作用 (2009)
  • Author(s): 内林瑠美、嶋澤雅光、鶴間一寛、原英彰
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] In vitro およびin vivo 網膜神経節細胞死に対する新規カルパイン阻害剤 SNJ-1945 の作用 (2009)
  • Author(s): 嶋澤雅光、末森晋典、井口勇太、松永望、中島佳美、岡隆之、山本哲也、原英彰
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] 小胞体ストレス誘発網膜神経節細胞死に対するSUN N8075の作用 (2008)
  • Author(s): 嶋澤 雅光
  • Organizer: 第28回日本眼薬理学会
  • Place of Presentation: ホテルグランヴィア岡山
  • Year and Date: 2008-09-20
• [Presentation] Protectiveeffect of SUN N8075 on endoplasmicreticulum stress-induced cell death in SH-SY5Y cells. (2008)
  • Author(s): 嶋澤雅光, 原英彰
  • Organizer: Neuroscience 2008
  • Place of Presentation: Washington, DC
• [Presentation] 小胞体ストレス誘発網膜神経節細胞死に対するSUN N8075 の作用 (2008)
  • Author(s): 嶋澤雅光、内林瑠美、原英彰
  • Organizer: 第28回日本眼薬理学会
  • Place of Presentation: 岡山