New strategy for lissencephaly therapeutic medicine development.

• Project/Area Number: 22390056
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Osaka City University
• Principal Investigator: YAMADA Masami 大阪市立大学, 大学院・医学研究科, 准教授 (10322851)
• Co-Investigator(Kenkyū-buntansha): KATAOKA Yosuke 独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター・細胞機能評価研究チーム, チームリーダー (40291033)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2012: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2010: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
• Keywords: LIS1 / カルパイン阻害剤 / 滑脳症 / 神経遊走 / 細胞内物質輸送 / 細胞質ダイニン / カルパイン 阻害薬 / 神経細胞遊走 / 微小管モータータンパク質 / タンパク質分解酵素 / カルパイン阻害薬 / 低分子量GTPase Rab6

Research Abstract

Toward a therapeutic intervention of lissencephaly, we applied a novel calpain inhibitor, SNJ1945. Peri-natal or post-natal treatment with SNJ1945 rescued defective neuronal migration in Lis1^+/^- mice, impaired behavioral performance. Thus, SNJ1945 is a

Research Products

• [Journal Article] Post-natal therapeutic intervention for lissencephaly using a blood-brain-barrier permeable calpain inhibitor (2013)
  • Author(s): Shiori Toba, Yasuhisa Tamura, Kanako Kumamoto, Masami Yamada, Keizo Takao, Satoko Hattori, Tsuyoshi Miyakawa, Yosky Kataoka, Mitsuyoshi Azuma, Kiyoshi Hayasaka, Masano Amamoto, Keiko Tominaga, Anthony Wynshaw-Boris, Mitsuhiro Kato and Shinji Hirotsune
  • Journal Title: SNJ1945 Scientific Reports Volume: 3 Issue: 1 Pages: 1224-1224
  • DOI: 10.1038/srep01224
  • Peer Reviewed
• [Journal Article] LIS1による細胞内ロジスティクスと滑脳症発症メカニズム (2013)
  • Author(s): 山田雅巳
  • Journal Title: 新学術領域研究・細胞内ロジスティクス班・ニュースレター Pages: 3-7
• [Journal Article] LIS1による細胞内ロジスティクスと滑脳症発症メカニズム (2013)
  • Author(s): 山田雅巳
  • Journal Title: 新学術領域研究・細胞内ロジスティクス班・ ニュースレター Volume: 3 Pages: 3-7
• [Journal Article] 蛍光一分子イメージングを用いたLIS1の細胞内ロジスティクスと滑脳症発症機構の解明 (2011)
  • Author(s): 山田雅巳
  • Journal Title: 物質・デバイス領域共同研究拠点研究成果報告集 Pages: 77-78
• [Journal Article] カルパイン阻害剤による滑脳症の治療 (2011)
  • Author(s): 山田雅巳
  • Journal Title: 上原記念生命科学財団・研究報告集 Volume: vol.25 Pages: 71-71
• [Journal Article] LIS1による細胞内ロジスティクスと滑脳症の関係 (2011)
  • Author(s): 山田雅巳
  • Journal Title: 生物物理 Volume: vol.51(6) Pages: 268-269
  • Peer Reviewed
• [Journal Article] LIS1による細胞内ロジスティクスと滑脳症発症の関係 (2011)
  • Author(s): 山田雅巳
  • Journal Title: 生物物理 Volume: 51(6) Pages: 268-269
  • NAID: 10030037995
  • Peer Reviewed
• [Journal Article] A novel strategy for therapeutic intervention for the genetic disease; Preventing proteolytic cleavage using small chemical compound. (2010)
  • Author(s): Masami Yamada, Shinji Hirotsune and Anthony Wynshaw-Boris
  • Journal Title: The International Journal of Biochemistry and Cell Biology Volume: vol. 42(9) Pages: 1401-1407
  • Peer Reviewed
• [Journal Article] A therapeutic intervention of gene disease by augmented recycling of target genes. (2010)
  • Author(s): Masami Yamada, Shinji Hirotsune and Anthony Wynshaw-Boris
  • Journal Title: Future Neurology Volume: vol. 5(1) Pages: 5-8
  • Peer Reviewed
• [Journal Article] The essential role of LIS1, NDEL1 and Aurora-A in polarity formation and microtubules organization during neurogenesis. (2010)
  • Author(s): Masami Yamada, Shinji Hirotsune and Anthony Wynshaw-Boris
  • Journal Title: Focal Adhesion and migration Volume: vol. 4(2) Pages: 180-184
  • Peer Reviewed
• [Journal Article] Functional dissection on LIS1 and NDEL1 towards understanding the molecular mechanism of cytoplasmic dynein regulation. (2010)
  • Author(s): Takayuki Torisawa, Akiko Nakayama, Ken'ya Furuta, Masami Yamada, Shinji Hirotsune, Yoko Y.Toyoshima
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 1959-1965
  • Peer Reviewed
• [Journal Article] A novel strategy for therapeutic intervention for the genetic disease ; Preventing proteolytic cleavage using small chemical compound. (2010)
  • Author(s): Masami Yamada, Shinji Hirotsune, Anthony Wynshaw-Boris
  • Journal Title: The International Journal of Biochemistry and Cell Biology Volume: 42 Pages: 1401-1407
  • Peer Reviewed
• [Journal Article] A therapeutic intervention of gene disease by augmented recycling of target genes. (2010)
  • Author(s): Masami Yamada, Shinji Hirotsune, Anthony Wynshaw-Boris
  • Journal Title: Future Neurology Volume: 5 Pages: 5-8
  • Peer Reviewed
• [Journal Article] The essential role of LIS1, NDEL1 and Aurora-A in polarity formation and microtubules organization during neurogenesis. (2010)
  • Author(s): Masami Yamada, Shinji Hirotsune, Anthony Wynshaw-Boris
  • Journal Title: Focal Adhesion and migration Volume: 4 Pages: 180-184
  • Peer Reviewed
• [Journal Article] Rab6a releases LIS1 from a dynein idling complex and activates dynein for retrograde movement.
  • Author(s): Masami Yamada, Kanako Kumamoto, Shintaro Mikuni, Yoshiyuki Arai, Masataka Kinjo, Takeharu Nagai, Yoshikazu Tsukasaki, Tomonobu M. Watanabe, Mitsuru Fukui, Mingyue Jin, Shiori Toba and Shinji Hirotsune
  • Journal Title: Nature Communications Volume: (in press)
  • Peer Reviewed
• [Presentation] カルパイン阻害薬のin vitro神経細胞遊走活性による探索 (2013)
  • Author(s): 山田雅巳
  • Organizer: 科学技術振興機構(JST)・新技術説明会優良シーズ発表会
  • Place of Presentation: 東京
  • Year and Date: 2013-02-25
• [Presentation] Rab6a releases LIS1 from a dynein idling complex and activates dynein for retrograde movement. (2012)
  • Author(s): Masami Yamada
  • Organizer: 第85回日本生化学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-16
• [Presentation] Rab6a releases LIS1 from a dynein idling complex and activates dynein for retrograde movement. (2012)
  • Author(s): Masami Yamada
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-13
• [Presentation] LIS1による細胞内ロジスティックスと滑脳症発症の関係 文部科学省 科学研究費 「新学術領域研究」 (2012)
  • Author(s): 山田雅巳
  • Organizer: 第4回「細胞内ロジスティックス」班会議
  • Place of Presentation: 仙台
  • Year and Date: 2012-06-15
• [Presentation] Inhibition of calpain increases LIS1(PAFAH1B1) and partially rescues in vivo phenotypes in a mouse model of lissencephaly. (2011)
  • Author(s): Masami Yamada, Takako Takitoh, Shinji Hirotsune
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-17
• [Presentation] Inhibition of calpain increases LIS1 (PAFAH1B1) and partially rescues in viro phenotypes in a mouse model of lissencephaly (2011)
  • Author(s): 山田雅巳
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシッコ横浜(横浜)
  • Year and Date: 2011-12-17
• [Presentation] Inhibition of calpain increases LIS1(PAFAH1B1) and partially rescues in vivo phenotypes in a mouse model of lissencephaly. (2011)
  • Author(s): Masami Yamada, Takako Takitoh, Shinji Hirotsune
  • Organizer: 第84回日本生化学会年会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] Inhibition of calpain increases LIS1 (PAFAH1B1) and partially rescues in vivo phenotypes in a mouse model of lissencephaly (2011)
  • Author(s): 山田雅巳
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2011-09-23
• [Presentation] Inhibition of calpain increases LIS1(PAFAH1B1) and partially rescues in vivo phenotypes in a mouse model of lissencephaly. (2011)
  • Author(s): Masami Yamada
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2011-06-29
• [Presentation] Inhibition of calpain increases LIS1 (PAFAH1B1) and partially rescues in vivo phenotypes in a mouse model of lissencephaly (2011)
  • Author(s): 山田雅巳
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌(北海道大学)
  • Year and Date: 2011-06-29
• [Presentation] LIS1による細胞内ロジスティックス 滑脳症発症の関係 文部科学省 科学研究費 「新学術領域研究」 (2011)
  • Author(s): 山田雅巳
  • Organizer: 第3回「細胞内ロジスティックス」 班会議
  • Place of Presentation: 三重
  • Year and Date: 2011-06-01
• [Presentation] LIS1による細胞内ロジスティックスと滑脳症発症の関係 (2011)
  • Author(s): 山田雅巳
  • Organizer: 新学術領域研究第3回細胞内ロジスティクス班会議
  • Place of Presentation: 鳥羽シーサイドホテル(三重)
  • Year and Date: 2011-06-01
• [Presentation] タンパク質分解酵素カルパインの阻害薬は滑脳症モデル(LIS1ヘテロ欠損) マウスにおいてその症状を改善した (2010)
  • Author(s): 山田雅巳
  • Organizer: 大阪市医学会例会
  • Place of Presentation: 大阪市立大学医学部
  • Year and Date: 2010-10-21
• [Presentation] A novel mechanism of plus-end- directed transport of cytoplasmic dynein and dynactins by kinesin-1.The role(s) of LIS1 and mNUDC in this process. (2010)
  • Author(s): Masami Yamada
  • Organizer: International Symposium on Single-molecule nano detection and its application to life science
  • Place of Presentation: Hyogo, Awaji
  • Year and Date: 2010-04-17
• [Presentation] 低分子量GTPase Rab6Aによる細胞質ダイニンの活性化メカニズムの解析
  • Author(s): 山田雅巳
  • Organizer: 第35回 日本分子生物学会
  • Place of Presentation: マリンメッセ福岡
• [Presentation] 低分子量GTPase Rab6Aによる細胞質ダイニンの活性化メカニズムの解析
  • Author(s): 山田雅巳
  • Organizer: 第85回 日本生化学会大会
  • Place of Presentation: マリンメッセ福岡
• [Presentation] ＬＩＳ１による細胞内ロジスティクスと滑脳症発症の関係
  • Author(s): 山田雅巳
  • Organizer: 第4回 新学術領域研究「細胞内ロジスティックス」班会議
  • Place of Presentation: 仙台市太白区秋保町秋保温泉岩沼屋
• [Remarks] 大阪市立大学・大学院医学研究科 細胞機能制御学
  • URL: http://www.med.osaka-cu.ac.jp/biochem2/
• [Remarks] 理化学研究所ライフサイエンス技術基盤研究センター・細胞機能評価研究チーム
  • URL: http://www.riken.jp/research/labs/clst/biofunct_dyn_img/img_funct/cell_funct_img/
• [Remarks]
  • URL: http://www.med.osaka-cu.ac.jp/biochem2/
• [Remarks]
  • URL: http://www.med.osaka-cu.ac.jp/biochem2/
• [Patent(Industrial Property Rights)] 神経細胞の遊走障害を伴う疾患の判定方法 (2013)
  • Inventor(s): 山田 雅巳
  • Industrial Property Rights Holder: 大阪市立大学
  • Filing Date: 2013-02-05
• [Patent(Industrial Property Rights)] 神経細胞の遊走障害を伴う 疾患の判別方法 (2013)
  • Inventor(s): 山田雅巳
  • Industrial Property Rights Holder: 大阪市立大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-02-05