Researcher Profile and Settings

researchmap

https://researchmap.jp/read0165637

Research funding number

10345043

Research Interests

• ホスフォイノシチド
• ガンマセクレターゼ
• アルツハイマー病
• アミロイドβ
• phosphoinositides
• gamma-secretase
• Alzheimer Disease
• Amyloid beta protein

Research Areas

• Life sciences / Neuroanatomy and physiology

Research History

• 1998-1999 Glycosilation of GPI anchored cell adhesion protein
• 1999-2002 Phosphoinositide signaling
• 2002-present Production amyloid beta protein

Research Experience

• The University of Tokyo, Faculty of Medicine, 2002 - 2007
• UCSD 博士研究員, 1999/09 - 2002
• UCSD客員研究員, 1998/08 - 1999/08
• 日本学術振興会特別研究員, 1998/04 - 1999/08

Association Memberships

• 米国神経科学会
• 日本分子生物学会
• SFN
• Molecular Biology Society of Japan

Committee Memberships

• 代議委員, 2013 - Today, 日本認知症学会, Society

Awards

• 学会賞
  Nov. 2022, 一般社団法人日本認知症学会
• 神経伝達機構と疾患研究 優秀賞受賞 財団法人パブリックヘルスリサーチセンター
  2006

Published Papers

• A tailored tetravalent peptide displays dual functions to inhibit amyloid β production and aggregation.
  Sato W; Watanabe-Takahashi M; Murata T; Utsunomiya-Tate N; Motoyama J; Anzai M; Ishihara S; Nishioka N; Uchiyama H; Togashi J; Nishihara S; Kawasaki K; Saito T; Saido T. C; Funamoto S*; Nishikawa K*
  Commun. Biol., 6(1)383(1) 383 - 383, Apr. 2023, Scientific journal
  

  DOI URL
• The senile plaque: Morphological differences in APP knock-in mice brains by fixatives.
  Rikuya Yoshimura; Tomohiro Miyasaka; Satoru Funamoto; Takashi Saito; Takaomi C Saido; Masaya Ikegawa; Nobuto Kakuda
  Brain and behavior, e2953 , 06 Mar. 2023, Scientific journal
  

  DOI URL
• A nontoxigenic form of Shiga toxin 2 suppresses the production of amyloid β by altering the intracellular transport of amyloid precursor protein through its receptor-binding B-subunit
  Waka Sato; Miho Watanabe-Takahashi; Takashi Hamabata; Koichi Furukawa; Satoru Funamoto; Kiyotaka Nishikawa
  Biochemical and Biophysical Research Communications, Elsevier BV, 557 247 - 253, Jun. 2021, Scientific journal
  

  DOI URL
• A potential defense mechanism against amyloid deposition in cerebellum
  Shahnur Alam; Masaki Nakano; Seiko Ishihara; Nobuto Kakuda; Tomohiro Miyasaka; Hina Uchiyama; Yuuna Shirai; Mohammad Moniruzzaman; Takashi Saito; Takaomi C. Saido; Masaki Nishimura; Satoru Funamoto
  Biochemical and Biophysical Research Communications, 535 25 - 32, 08 Jan. 2021, Scientific journal
  

  DOI URL
• Successive cleavage of β-amyloid precursor protein by γ-secretase
  Satoru Funamoto; Shinji Tagami; Masayasu Okochi; Maho Morishima-Kawashima
  Seminars in Cell & Developmental Biology, Elsevier BV, 105 64 - 74, Sep. 2020, Scientific journal
  

  DOI URL
• γ-Secretase Activity Is Associated with Braak Senile Plaque Stages.
  Nobuto Kakuda; Haruyasu Yamaguchi; Kohei Akazawa; Saori Hata; Toshiharu Suzuki; Hiroyuki Hatsuta; Shigeo Murayama; Satoru Funamoto; Yasuo Ihara
  The American journal of pathology, 190(6) 1323 - 1331, Jun. 2020, Scientific journal
  

  DOI URL
• Curcumin Derivative GT863 Inhibits Amyloid-Beta Production via Inhibition of Protein N-Glycosylation.
  Yasuomi Urano; Mina Takahachi; Ryo Higashiura; Hitomi Fujiwara; Satoru Funamoto; So Imai; Eugene Futai; Michiaki Okuda; Hachiro Sugimoto; Noriko Noguchi
  Cells, 9(2), 03 Feb. 2020, Scientific journal
  

  DOI URL
• Glycosylation status of nicastrin influences catalytic activity and substrate preference of γ-secretase
  Mohammad Moniruzzaman; Seiko Ishihara; Mika Nobuhara; Hidekazu Higashide; Satoru Funamoto
  Biochemical and Biophysical Research Communications, Elsevier B.V., 502(1) 98 - 103, 07 Jul. 2018, Scientific journal
  

  DOI URL
• Pleckstrin homology domain of p210 BCR-ABL interacts with cardiolipin to regulate its mitochondrial translocation and subsequent mitophagy
  Kentaro Shimasaki; Miho Watanabe-Takahashi; Masato Umeda; Satoru Funamoto; Yoshiro Saito; Noriko Noguchi; Keigo Kumagai; Kentaro Hanada; Fujiko Tsukahara; Yoshiro Maru; Norihito Shibata; Mikihiko Naito; Kiyotaka Nishikawa
  Genes to Cells, Wiley, 23(1) 22 - 34, Jan. 2018, Scientific journal
  

  URLDOI URL
• Alanine substitutions in the GXXXG motif alter C99 cleavage by gamma-secretase but not its dimerization
  Hidekazu Higashide; Seiko Ishihara; Mika Nobuhara; Yasuo Ihara; Satoru Funamoto
  JOURNAL OF NEUROCHEMISTRY, WILEY, 140(6) 955 - 962, Mar. 2017, Scientific journal
  

  DOI URL
• Affinity-Based Screening of Tetravalent Peptides Identifies SubtypeS-elective Neutralizers of Shiga Toxin 2d, a Highly Virulent Subtype, by Targeting a Unique Amino Acid Involved in Its Receptor Recognition
  Takaaki Mitsui; Miho Watanabe-Takahashi; Eiko Shimizu; Baihao Zhang; Satoru Funamoto; Shinji Yamasaki; Kiyotaka Nishikawa
  INFECTION AND IMMUNITY, AMER SOC MICROBIOLOGY, 84(9) 2653 - 2661, Sep. 2016, Scientific journal
  

  DOI URL
• アルツハイマー病とは
  舟本 聡
  Clinical Neuroscience, (34) 962 - 966, 2016
• The A673T mutation in the amyloid precursor protein reduces the production of beta-amyloid protein from its beta-carboxyl terminal fragment in cells
  Asuka Kokawa; Seiko Ishihara; Hitomi Fujiwara; Mika Nobuhara; Minori Iwata; Yasuo Ihara; Satoru Funamoto
  ACTA NEUROPATHOLOGICA COMMUNICATIONS, BIOMED CENTRAL LTD, 3 66 , Nov. 2015
  

  DOI URL
• Raft-nonassociated γ-secretase活性による脳内Aβ蓄積
  角田 伸人; 山口 晴保; 赤澤 宏平; 初田 裕幸; 村山 繁雄; 舟本 聡; 井原 康夫
  Dementia Japan, (一社)日本認知症学会, 29(3) 422 - 422, Sep. 2015
• γ-Secretase associated with lipid rafts: Multiple interactive pathways in the stepwise processing ofβ-carboxylterminal fragment
  Nobutaka Matsumura; Mako Takami; Masayasu Okochi; Satoko Wada-Kakuda; Hitomi Fujiwara; Shinji Tagami; Satoru Funamoto; Yasuo Ihara; Maho Morishima-Kawashima
  Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology Inc., 289(8) 5109 - 5121, 21 Feb. 2014, Scientific journal
  

  DOI URL
• Modulation of Lipid Kinase PI4KII alpha Activity and Lipid Raft Association of Presenilin 1 Underlies gamma-Secretase Inhibition by Ginsenoside (20S)-Rg3
  Min Suk Kang; Seung-Hoon Baek; Yoon Sun Chun; A. Zenobia Moore; Natalie Landman; Diego Berman; Hyun Ok Yang; Maho Morishima-Kawashima; Satoko Osawa; Satoru Funamoto; Yasuo Ihara; Gilbert Di Paolo; Jeong Hill Park; Sungkwon Chung; Tae-Wan Kim
  JOURNAL OF BIOLOGICAL CHEMISTRY, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 288(29) 20868 - 20882, Jul. 2013, Scientific journal
  

  DOI URL
• Substrate ectodomain is critical for substrate preference and inhibition of γ-secretase
  Satoru Funamoto; Toru Sasaki; Seiko Ishihara; Mika Nobuhara; Masaki Nakano; Miho Watanabe-Takahashi; Takashi Saito; Nobuto Kakuda; Tomohiro Miyasaka; Kiyotaka Nishikawa; Takaomi C. Saido; Yasuo Ihara
  Nature Communications, 4 2529 , 2013, Scientific journal
  

  DOI URL
• Potent amyloidogenicity and pathogenicity of A beta 43
  Takashi Saito; Takahiro Suemoto; Nathalie Brouwers; Kristel Sleegers; Satoru Funamoto; Naomi Mihira; Yukio Matsuba; Kazuyuki Yamada; Per Nilsson; Jiro Takano; Masaki Nishimura; Nobuhisa Iwata; Christine Van Broeckhoven; Yasuo Ihara; Takaomi C. Saido
  NATURE NEUROSCIENCE, NATURE PUBLISHING GROUP, 14(8) 1023 - U120, Aug. 2011, Scientific journal
  

  DOI URL
• The production ratios of AICD epsilon 51 and A beta 42 by intramembrane proteolysis of beta APP do not always change in parallel
  Kohji Mori; Masayasu Okochi; Shinji Tagami; Taisuke Nakayama; Kanta Yanagida; Takashi S. Kodama; Shin-ichi Tatsumi; Kana Fujii; Hitoshi Tanimukai; Ryota Hashimoto; Takashi Morihara; Toshihisa Tanaka; Takashi Kudo; Satoru Funamoto; Yasuo Ihara; Masatoshi Takeda
  PSYCHOGERIATRICS, WILEY-BLACKWELL PUBLISHING, INC, 10(3) 117 - 123, Sep. 2010, Scientific journal
  

  DOI URL
• gamma-Secretase: Successive Tripeptide and Tetrapeptide Release from the Transmembrane Domain of beta-Carboxyl Terminal Fragment
  Mako Takami; Yu Nagashima; Yoshihisa Sano; Seiko Ishihara; Maho Morishima-Kawashima; Satoru Funamoto; Yasuo Ihara
  JOURNAL OF NEUROSCIENCE, SOC NEUROSCIENCE, 29(41) 13042 - 13052, Oct. 2009, Scientific journal
  

  DOI URL
• Phosphoinositides suppress gamma-secretase in both the detergent-soluble and -insoluble states
  Satoko Osawa; Satoru Funamoto; Mika Nobuhara; Satoko Wada-Kakuda; Masafumi Shimojo; Sosuke Yagishita; Yasuo Ihara
  JOURNAL OF BIOLOGICAL CHEMISTRY, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 283(28) 19283 - 19292, Jul. 2008, Scientific journal
  

  DOI URL
• Enzymatic characteristics of I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains - Familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta
  Masafumi Shimojo; Naruhiko Sahara; Tatsuya Mizoroki; Satoru Funamoto; Maho Morishima-Kawashima; Takashi Kudo; Masatoshi Takeda; Yasuo Ihara; Hiroshi Ichinose; Akihiko Takashima
  JOURNAL OF BIOLOGICAL CHEMISTRY, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 283(24) 16488 - 16496, Jun. 2008, Scientific journal
  

  DOI URL
• Active gamma-secretase complexes contain only one of each component
  Toru Sato; Thekla S. Diehl; Saravanakumar Narayanan; Satoru Funamoto; Yasuo Ihara; Bart De Strooper; Harald Steiner; Christian Haass; Michael S. Wolfe
  JOURNAL OF BIOLOGICAL CHEMISTRY, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 282(47) 33985 - 33993, Nov. 2007, Scientific journal
  

  DOI URL
• Equimolar production of amyloid beta-protein and amyloid precursor protein intracellular domain from beta-carboxyl-terminal fragment by beta-secretase
  N Kakuda; S Funamoto; S Yagishita; M Takami; S Osawa; N Dohmae; Y Ihara
  JOURNAL OF BIOLOGICAL CHEMISTRY, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 281(21) 14776 - 14786, May 2006, Scientific journal
  

  DOI URL
• Dictyostelium PAKc is required for proper chemotaxis
  S Lee; F Rivero; KC Park; E Huang; S Funamoto; RA Firtel
  MOLECULAR BIOLOGY OF THE CELL, AMER SOC CELL BIOLOGY, 15(12) 5456 - 5469, Dec. 2004, Scientific journal
  

  DOI URL
• Truncated carboxyl-terminal fragments of beta-amyloid precursor protein are processed to amyloid beta-proteins 40 and 42
  S Funamoto; M Morshima-Kawashima; Y Tanimura; N Hirotani; TC Saido; Y Ihara
  BIOCHEMISTRY, AMER CHEMICAL SOC, 43(42) 13532 - 13540, Oct. 2004, Scientific journal
  

  DOI URL
• Receptor-mediated regulation of PI3Ks confines PI(3,4,5)P-3 to the leading edge of chemotaxing cells
  YE Huang; M Iijima; CA Parent; S Funamoto; RA Firtel; P Devreotes
  MOLECULAR BIOLOGY OF THE CELL, AMER SOC CELL BIOLOGY, 14(5) 1913 - 1922, May 2003, Scientific journal
  

  DOI URL
• cAMP-dependent protein kinase regulates Polysphondylium pallidum development
  S Funamoto; C Anjard; W Nellen; H Ochiai
  DIFFERENTIATION, BLACKWELL VERLAG GMBH, 71(1) 51 - 61, Jan. 2003, Scientific journal
• Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis
  S Funamoto; R Meili; S Lee; L Parry; RA Firtel
  CELL, CELL PRESS, 109(5) 611 - 623, May 2002, Scientific journal
• Signaling pathways controlling cell polarity and chemotaxis
  CY Chung; S Funamoto; RA Firtel
  TRENDS IN BIOCHEMICAL SCIENCES, ELSEVIER SCIENCE LONDON, 26(9) 557 - 566, Sep. 2001
• Role of phosphatidylinositol 3 ' kinase and a downstream pleckstrin homology domain-containing protein in controlling chemotaxis in Dictyostelium
  S Funamoto; K Milan; R Meili; RA Firtel
  JOURNAL OF CELL BIOLOGY, ROCKEFELLER UNIV PRESS, 153(4) 795 - 809, May 2001, Scientific journal
• An SH2-domain-containing kinase negatively regulates the phosphatidylinositol-3 kinase pathway
  J Moniakis; S Funamoto; M Fukuzawa; J Meisenhelder; T Araki; T Abe; R Meili; T Hunter; J Williams; RA Firtel
  GENES & DEVELOPMENT, COLD SPRING HARBOR LAB PRESS, 15(6) 687 - 698, Mar. 2001, Scientific journal
• Cell-cell adhesion protein gp64 of Polysphondylium pallidum.
  Ochiai, H; Saito, T; Funamoto, S; SAITO TAMAO
  Dictyostelium : a model system for cell and developmental biology : proceedings of the Yamada Conference XLVI on International Dictyostelium Conference, held on October 14-18, 1996, in Sendai, Japan, Universal Academy Press, 123 - 136, Oct. 1997
• Antisense RNA inactivation of gene expression of a cell-cell adhesion protein (gp64) in the cellular slime mold Polysphondylium pallidum
  S Funamoto; H Ochiai
  JOURNAL OF CELL SCIENCE, COMPANY OF BIOLOGISTS LTD, 109 1009 - 1016, May 1996, Scientific journal
• Simple method for detection of sense and antisense transcripts
  S Funamoto; H Ochiai
  SEIKAGAKU, JAPAN BIOCHEMICAL SOC, 68(4) 303 - 305, Apr. 1996, Scientific journal
• Dimer formation of a cell-cell adhesion protein, gp64 of the cellular slime mold, Polysphondylium pallidum
  H Ochiai; K Hata; T Saito; S Funamoto; N Nakata
  PLANT AND CELL PHYSIOLOGY, JAPANESE SOC PLANT PHYSIOLOGISTS, 37(2) 135 - 139, Mar. 1996, Scientific journal
• Effects of tunicamycin on the development of Dictyostelium discoideum
  Ochiai H; Saito T; Funamoto S; Fukuzawa M; Nakata N; Kijimoto-Ochiai S; Arisaka F
  Animal Biol., 4 3 - 11, 1995

MISC

• Alanine substitutions in the GXXXG motif alter C99 cleavage by gamma-secretase but not its dimerization
  Hidekazu Higashide; Seiko Ishihara; Mika Nobuhara; Yasuo Ihara; Satoru Funamoto
  JOURNAL OF NEUROCHEMISTRY, WILEY, 140(6) 955 - 962, Mar. 2017
  

  DOI URL
• P210型BCR‐ABL PHドメインのリガンド特性およびその病理的意義の解明
  島崎健太朗; 高橋美帆; 梅田真郷; 舟本聡; 斎藤芳郎; 野口範子; 熊谷圭吾; 花田賢太郎; 塚原富士子; 丸義朗; 柴田識人; 内藤幹彦; 内藤幹彦; 西川喜代孝
  日本生化学会大会(Web), 生命科学系学会合同年次大会運営事務局, 90th ROMBUNNO.1PT26‐07(2P‐0039) (WEB ONLY) - 0039)], 2017
  

  URL
• アミロイドβたんぱく質変異、アルツハイマー病の発症防ぐ-同志社大が解明
  舟本 聡
  日刊工業新聞, 2015
• アルツハイマー型認知症の進行・治療機序
  舟本 聡舟本
  日本医事新報, 4768 64 - 65, 2015
• Regulation of presenilin/gamma-secretase function; towards intervention of Alzheimer disease in future
  田上真次; 大河内正康; 西村正樹; 舟本聡; 富田泰輔; 武田雅俊
  日本生物学的精神医学会誌, 25(1), 2014
• Modulation of Lipid Kinase PI4KII alpha Activity and Lipid Raft Association of Presenilin 1 Underlies gamma-Secretase Inhibition by Ginsenoside (20S)-Rg3
  Min Suk Kang; Seung-Hoon Baek; Yoon Sun Chun; A. Zenobia Moore; Natalie Landman; Diego Berman; Hyun Ok Yang; Maho Morishima-Kawashima; Satoko Osawa; Satoru Funamoto; Yasuo Ihara; Gilbert Di Paolo; Jeong Hill Park; Sungkwon Chung; Tae-Wan Kim
  JOURNAL OF BIOLOGICAL CHEMISTRY, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 288(29) 20868 - 20882, Jul. 2013
  

  DOI URL
• 対談：菅原文太 日本人の底力「アルツハイマー病、抑制物質の開発とこれからの実用性」
  舟本 聡
  ニッポン放送, 2013
• 記事：アルツハイマー抑える物質開発 同志社大、治療に期待
  舟本 聡
  佐賀新聞, 2013
• 記事：アルツハイマー抑える物質開発 同志社大、治療に期待
  舟本 聡
  北海道新聞, 2013
• 記事：アルツハイマー抑える物質開発 同志社大、治療に期待
  舟本 聡
  徳島新聞, 2013
• 記事：アルツハイマー病 原因物質だけ抑制
  舟本 聡
  京都新聞, 2013
• 記事：ｱﾙﾂﾊｲﾏｰ治療に光 同大ﾁｰﾑ副作用減らし原因物質抑制
  舟本 聡
  毎日新聞, 2013
• 記事：アルツハイマー抑制物質開発 同大、治療への応用期待
  舟本 聡
  産經新聞, 2013
• 記事：アルツハイマー原因物質抑える 同志社大が開発
  舟本 聡
  日本経済新聞, 2013
• 記事：副作用少ない治療薬へ全身＝ｱﾙﾂﾊｲﾏｰ病で新技術ー同志社大
  舟本 聡
  時事通信, 2013
• 記事：アルツハイマー抑える物質開発 同志社大、治療に期待
  舟本 聡
  共同通信, 2013
• 解説記事：患者さん由来iPS細胞でアルツハイマー病の病態を解明 京都大学
  舟本 聡
  京都新聞, 2013
• Substrate ectodomain is critical for substrate preference and inhibition of γ-secretase
  Satoru Funamoto; Toru Sasaki; Seiko Ishihara; Mika Nobuhara; Masaki Nakano; Miho Watanabe-Takahashi; Takashi Saito; Nobuto Kakuda; Tomohiro Miyasaka; Kiyotaka Nishikawa; Takaomi C. Saido; Yasuo Ihara
  Nature Communications, 4(2529) doi:10.1038/ncomms3529 , 2013
  

  DOI URL
• γ-Secretase-Dependent Proteolysis of Transmembrane Domain of Amyloid Precursor Protein: Successive Tri- and Tetrapeptide Release in Amyloid β-Protein Production.
  Int J Alzheimers Dis, 2012
  

  DOI URL
• γセクレターゼによる膜内切断-トリペプチドの放出とAβ産生-
  舟本 聡
  DEMENTIA JAPAN, 26 60 - 66, 2012
• γ-Secretase-dependent proteolysis of transmembrane domain of amyloid precursor protein: Successive tri-and tetrapeptide release in amyloid β-protein production
  Mako Takami; Satoru Funamoto
  International Journal of Alzheimer's Disease, 2012, Book review
  

  DOI URL
• The production ratios of AICDε51 and Aβ42 by intramembrane proteolysis of βAPP do not always change in parallel
  MORI Kohji; OKOCHI Masayasu; TAGAMI Shinji; NAKAYAMA Taisuke; YANAGIDA Kanta; KODAMA Takashi S.; TATSUMI Shin-ichi; FUJII Kana; TANIMUKAI Hitoshi; HASHIMOTO Ryota; MORIHARA Takashi; TANAKA Toshihisa; KUDO Takashi; FUNAMOTO Satoru; IHARA Yasuo; TAKEDA Masatoshi
  Psychogeriatrics, 10(3) 117 - 123, 01 Sep. 2010
• ε切断からみたγセクレターゼ修飾薬の作用点
  森 康治; 大河内 正康; 田上 真次; 中山 泰亮; 柳田 寛太; 児玉 高志; 辰巳 真一; 藤井 加奈; 谷向 仁; 森原 剛史; 橋本 亮太; 田中 稔久; 工藤 喬; 舟本 聡; 井原 康夫; 武田 雅俊
  Dementia Japan, (一社)日本認知症学会, 24(3) 382 - 382, Sep. 2010
• γ-セクレターゼによるアミロイド前駆体蛋白質切断
  舟本 聡
  Pharma Medica, 28 35 - 38, 2010
• gamma-Secretase: Successive Tripeptide and Tetrapeptide Release from the Transmembrane Domain of beta-Carboxyl Terminal Fragment
  Mako Takami; Yu Nagashima; Yoshihisa Sano; Seiko Ishihara; Maho Morishima-Kawashima; Satoru Funamoto; Yasuo Ihara
  JOURNAL OF NEUROSCIENCE, SOC NEUROSCIENCE, 29(41) 13042 - 13052, Oct. 2009
  

  DOI URL
• Phosphoinositides suppress gamma-secretase in both the detergent-soluble and -insoluble states
  Satoko Osawa; Satoru Funamoto; Mika Nobuhara; Satoko Wada-Kakuda; Masafumi Shimojo; Sosuke Yagishita; Yasuo Ihara
  JOURNAL OF BIOLOGICAL CHEMISTRY, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 283(28) 19283 - 19292, Jul. 2008
  

  DOI URL
• Enzymatic characteristics of I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains - Familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta
  Masafumi Shimojo; Naruhiko Sahara; Tatsuya Mizoroki; Satoru Funamoto; Maho Morishima-Kawashima; Takashi Kudo; Masatoshi Takeda; Yasuo Ihara; Hiroshi Ichinose; Akihiko Takashima
  JOURNAL OF BIOLOGICAL CHEMISTRY, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 283(24) 16488 - 16496, Jun. 2008
  

  DOI URL
• Active gamma-secretase complexes contain only one of each component
  Toru Sato; Thekla S. Diehl; Saravanakumar Narayanan; Satoru Funamoto; Yasuo Ihara; Bart De Strooper; Harald Steiner; Christian Haass; Michael S. Wolfe
  JOURNAL OF BIOLOGICAL CHEMISTRY, AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 282(47) 33985 - 33993, Nov. 2007
  

  DOI URL
• How is beta-amyloid precursor protein cleaved in the membrane?
  Y Ihara; M Morishima-Kawashima; Y Qia; T Sato; S Funamoto; T Saido; N Hirotani
  JOURNAL OF NEUROCHEMISTRY, BLACKWELL PUBLISHING LTD, 88 4 - 4, Feb. 2004, Summary international conference
• PI3K and PTEN as regulators of chemotaxis
  R Meili; S Funamoto; RA Firtel
  MOLECULAR BIOLOGY OF THE CELL, AMER SOC CELL BIOLOGY, 13 47A - 47A, Nov. 2002, Summary international conference
• Finding their way - Role of P13K in directional sensing.
  RA Firtel; S Funamoto; R Meili
  DEVELOPMENTAL BIOLOGY, ACADEMIC PRESS INC ELSEVIER SCIENCE, 247(2) 484 - 485, Jul. 2002, Summary international conference
• Sensing and responding to directional signals: The role of P13 kinase in regulating chemotaxis.
  RA Firtel; CY Chung; S Funamoto; J Moniakis
  FASEB JOURNAL, FEDERATION AMER SOC EXP BIOL, 15(4) A3 - A3, Mar. 2001, Summary international conference
• MEMBRANE PROTEIN GP64 INHIBITS THE WHORL FORMATION OF Polysphondylium pallidum :
  FUNAMOTO S.; OCHIAI H.; SAITO T.
  Plant and cell physiology, Japanese Society of Plant Physiologists, 41 s209 , 2000
• Structural and functional analysis of gp64, a membrane protein of the cellular slime mold Polysphondylium pallidum
  T Saito; S Funamoto; H Ochiai
  SEIKAGAKU, JAPANESE BIOCHEMICAL SOC, 70(7) 537 - 542, Jul. 1998, Book review
• Functional Analysis of gp64, a Membrane Protein of Polysphondylium pallidum by Molecular Genetic Techniques
  FUNAMOTO Satoru; OCHIAI Hiroshi
  Plant and cell physiology, 39 S121 - S121, May 1998
• ニュース：
  舟本 聡
  NHK京都放送
• 記事：アルツハイマー抑える物質
  舟本 聡舟本
  朝日新聞

Books etc

• デブリン生化学
  丸善出版, 2013
• Equimolar production of Aβ and AICD from C99 by γ-secretase
  2006
• Equimolar production of Aβ and AICD from C99 by γ-secretase
  10th International Conference on Alzheimer's Disease and Related Disorders Alzheimer's Disease : New Advances, 2006
• Directional sensing : Subcellular targeting of GPCR downstream effectors during chemotaxis In : Cell Motility : From Molecules to Organisms
  2004
• Directional sensing : Subcellular targeting of GPCR downstream effectors during chemotaxis In : Cell Motility : From Molecules to Organisms
  John Wiley & Sons, Ltd, 2004
• 増感化学発光を用いたサザンハイブリダイゼーション
  脱アイソトープ実戦プロトコール 2 キット簡単編 ( 野村慎太郎・渡邊俊樹 監修 ) 秀潤社 東京, 1998
• "Cell-cell adhesion protein of Polysphondylium pallidum" In: Dictyostelium: A model system for cell and developmental biology
  1997
• "Cell-cell adhesion protein of Polysphondylium pallidum" In: Dictyostelium: A model system for cell and developmental biology
  University Academy Press Tokyo, 1997

Presentations

• 抗アミロイド療法としてのAPP特異的切断抑制
  舟本 聡
  第42回日本認知症学会学術集会, 26 Nov. 2023, Invited oral presentation
• 副作用のない抗アミロイド療法の開発
  舟本 聡
  第96回日本生化学会大会シンポジウム 2S03e, Nov. 2023, Invited oral presentation
• Potential determination mechanism of epsilon-cleavage sites: Implication for determinants of Abeta40 and Abeta42 product lines
  FUNAMOTO Satoru
  ADPD2017, 2017
• APP A673T mutation reduces not only b-cleavage but also g-cleavage of APP in cells
  FUNAMOTO Satoru
  ADPD2015, 2015
• アミロイドβの産生機序と産生抑制
  舟本 聡
  認知症の最新発症メカニズムと治療薬開発, 2015
• Binding gamma-secretase to substrates
  FUNAMOTO Satoru
  11th World Congress of Biological Psychiatry, 2014
• アミロイド仮説に基づくアルツハイマー病根本治療薬開発の現状と新しい治療戦略
  舟本 聡
  第１２９回日本薬理学会関東部会, 2013
• The ectodomain of substrate si critical for substrate-preference of g-secretase and for substrate-specific inhibiiton of Ab production
  FUNAMOTO Satoru
  ADPD2013, 2013
• Substrate-specific dual inhibition of b- and g-secretases by peptides binding to C99
  FUNAMOTO Satoru
  Neuroscience2012, 2012
• Semagacestatのin vitroデータ
  舟本 聡
  第31回日本認知症学会学術集会シンポジウム, 2012
• Semagacestatのin vitroデータ
  舟本 聡
  第31回日本認知症学会学術集会シンポジウム, 2012
• Amino-terminus of amyloid β protein is a potential target for substrate-specific dual inhibition of β- and γ-secretases
  舟本 聡
  Neuroscience2011, 2011
• CTF is an inefficient substrate for proteolysis by -secretase
  舟本 聡
  BMB2010 (work shop), 2010
• CTF is an inefficient substrate for proteolysis by -secretase
  舟本 聡
  International Conference on Alzheimer's Disease and Related Disorders, 2010
• γセクレターゼによる膜内切断機構 –トリペプチド放出とAβ産生-
  舟本 聡
  第２９回日本認知症学会学術集会シンポジウム, 2010
• Profinity eXact Fusion-Tagによる組換えγセクレターゼ基質の調製
  舟本 聡
  第１０回日本蛋白質科学会年会, 2010
• Loose membrane-bound endogenous factors might modulates the intramembrane cleavages of βAPP
  舟本 聡
  12th International Conference on Alzheimer's Disease and Related Disorders, 2009
• アミロイドβタンパク質産生機序 -- トリペプチド仮説の検証 --
  舟本 聡
  日本生化学会, 2009, 神戸
• γセクレターゼ活性におけるホスフォイノシチドの影響
  舟本 聡
  日本分子生物学会 / 日本生化学会 合同年会, 2007, 横浜
• Effects of phosphoinositides on γ-secretase activity in detergent soluble / insoluble states
  舟本 聡
  SFN 2007, 2007, San Diego, U.S.A.
• Effects of phosphoinositides on γ-secretase activity in detergent soluble / insoluble states
  舟本 聡
  日本認知症学会 学術集会, 2007, 大阪国際会議場
• Equimolar production of Aβ and AICD from C99 by γ-secretase
  舟本 聡
  10th International Conference on Alzheimer's Disease and Related Disorders, 2006, Madrid, Spain
• アミロイドβタンパク質40, 42の産生機序
  舟本 聡
  日本分子生物学会, 2003
• Relationship between g- and e-cleavage : CTF1-48 of e-cleaved amyloid precursor protein is linked to production of Ab42
  舟本 聡
  SFN 2003, 2003, New Orleans, USA
• アミロイドβタンパク質40、42産生機序 ： bCTFに対するe切断部位の変化がアミロイドβタンパク質の分子種を決定するか？
  舟本 聡
  日本痴呆学会 学術集会, 2003, 大田区産業プラザ

Industrial Property Rights

• Patent right
  Aβタンパク質特異的産生抑制剤
  舟本 聡
  特願2018-154788
• Patent right
  アミロイドβタンパク質特異的産生抑制ペプチド
  舟本 聡
  特許6168998
• Patent right
  AMYLOID β-PROTEIN-SPECIFIC PRODUCTION-INHIBITING POLYPEPTIDE
  US 9,045,525, B2
• Patent right
  AMYLOID β-PROTEIN-SPECIFIC PRODUCTION-INHIBITING POLYPEPTIDE
  WO2013108780 A1
• Patent right
  AMYLOID β-PROTEIN-SPECIFIC PRODUCTION-INHIBITING POLYPEPTIDE
  WO2013108780 A1

Research Projects

• Understanding of A potential defense mechanism against amyloid deposition in cerebellum
  舟本 聡
  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2022/04 -2025/03, Grant-in-Aid for Scientific Research (C), Doshisha University
• Identification of glycosylation site involving into substrate preference of gamma-secretase
  Funamoto Satoru; Moniruzzaman Mohammad
  Nicastrin is one of components of γ-secretase complex, catalyzes the cleavage of amyloid precursor protein to generate amyloid-β protein (Aβ). NCT becomes matured through complex glycosylation and play important role in γ-secretase activity. However, the role of NCT glycosylation on γ-secretase activity and substrate specificity is still unknown. We investigated the effect of NCT glycosylation on γ-secretase activity and substrate specificity in a group of glycosylation mutant lectin resistant CHO (Lec) cells. CHO Lec-1 cells lack glycosyltransferase-I, thus N-glycan on NCT are all oligomannose type. We found that mutant CHO Lec-1 and Lec-2 reduced γ-secretase activity in both cell-based and biochemical assays, and that CHO Lec-1 preferentially reduced Aβ generation. Our data suggests that thorough glycosylation of NCT is critical for enzymatic activity and substrate preference of γ-secretase., Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2016/04 -2019/03, Grant-in-Aid for Scientific Research (C), Doshisha University
• Characterization of the enzymatic properties of γ-secretase
  IHARA Yasuo; FUNAMOTO Satoru; MORISHIMA Maho
  How the cleavage proceeds within the membrane has long been enigmatic. We previously hypothesized that βCTF is cleaved first at the membrane-cytoplasm boundary, producing two long Ass, Aβ48 and Aβ49, which are processed further by releasing three residues at each step to produce Aβ42 and Aβ40, respectively. To test this hypothesis, we used LC-MS/MS to quantify the specific tripeptides that are postulated to be released. Using CHAPSO-reconstituted γ-secretase system, we confirmed that Aβ49 is converted to Aβ43/40 by successively releasing two or three tripeptides, and that Aβ48 is converted to Aβ42/38 by successively releasing two tripeptides or these plus an additional tetrapeptide., Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2005 -2009, Grant-in-Aid for Scientific Research on Priority Areas
• アミロイド前駆体タンパク質のガンマ切断部位を制御する因子の探索
  舟本 聡
  ガンマ切断部位を制御する因子のスクリーニングのため、ガンマセクレターゼの試験管内Aβ産生系の確立を試みた。培養細胞から調製した膜フラクションを界面活性剤CHAPSOで可溶化し、その遠心上清を膜抽出液とした。これに基質C99-FLAGを添加し、Aβの産生を検討した。Aβは反応時間依存的・基質濃度依存的に産生されることがわかった。この系ではAβ40、Aβ42、Aβ43、Aβ45、Aβ48、Aβ49の分子種が同定され、可溶化前の膜とは異なりAβ46の産生を確認できなかった。しかし、ガンマセクレターゼ活性はこれまで報告されている試験管内Aβ産生系と比較しても30倍以上あり、この系はAβ産生モデルとしてメカニズムの解明や阻害剤の開発への利用が期待できる。この成果は今年度はじめに雑誌the Journal of Biological Chemistryに受理され、その後国内外のさまざまな研究室でこの系が利用されている。 ホスファチジルイノシトールリン酸は脂質構成成分としては微量にしか含まれてないが、生体内でシグナル分子またはセカンドメッセンジャー前駆体として重要な機能を果たしている。ホスファチジルイノシトールリン酸がガンマセクレターゼにも影響を与えていることを考慮し、上記のガンマセクレターゼ測定系にホスファチジルイノシトールリン酸を添加し、産生されるAβとその分子種を調べた。その結果リン酸基数の上昇に伴い、Aβ産生が抑制されることを見いだした。他のリン脂質(ホスファチジルコリン)との混合で、Aβ42の産生が顕著になる条件を見いだした。, 日本学術振興会, 科学研究費助成事業, 2005 -2006, 若手研究(B), 東京大学
• ガンマセクレターゼの同定とアミロイドベータタンパク質Aβ42の産生機序
  舟本 聡
  今年度の本研究では、ガンマセクレターゼによるガンマ切断のイプシロン切断依存性を検証するため、予めガンマ切断部位からはじまるAPPカルボキシル末断片(CTF41-99)をCHO細胞に発現させて、イプシロン切断が起こるか否か検討した。その結果、細胞内からγCTFと伺じ移動度の断片が検出され、質量分析の結果CTF50-99であることがわかった。しかし、ガンマセクレターゼ特異的阻害剤(L-685,458)を細胞に処理しCTF50-99の検出を試みると、細胞は処理にも関わらずCTF50-99を産生することがわかった。このことはCTF41-99を発現させて得られたCTF50-99はガンマセクレターゼとは別の機構で生じていることを示し、ガンマセクレターゼによるガンマ切断のイプシロン切断依存性を反証するには到らなかった。以上の結果と昨年の成果を含めた論文がBiochemistry誌に受理された。 膜貫通部分の途中までを含むAPPのカルボキシル末端断片(CTF1-51)を細胞に発現させると、Aβ42が顕著に増加しAβ40が減少する。このCTF1-51を発現する細胞をAβ42の産生モデルとし、様々な条件でAβの産生能を調査した。まず、この細胞の膜フラクションを様々な界面活性剤で可溶化し、酵素活性(Aβ産生能)を測定した。通常のCTF1-99を発現する細胞の膜フラクションはDIGITONINで可溶化しても酵素活性を有することはないが、CTF1-51を発現する細胞の場合では酵素活性を有していた。また、産生されるAβ42の割合は依然高いままであった。一方、Blue Native PAGEにより可溶化フラクションを展開し、抗Nicastrin抗体でガンマセクレターゼ複合体を検出したところ、分子量44万に加えて30万〜25万付近にもバンドを検出した。通常のCTF1-99を発現する細胞の可溶化フラクションでは分子量44万のバンドのみ検出されることから、30万〜25万付近に現れるバンドはAβ42の産生に特異的なものと考えられる。, 日本学術振興会, 科学研究費助成事業, 2003 -2004, 若手研究(B), 東京大学
• Hyperphosphorylation and aggregation of tau protein, and neuronal death
  IHARA Yasuo; MORISHIMA Maho; FUNAMOTO Satoru; MIYASAKA Tomohiro; ITO Mamoru; FUJITA Shinobu
  Discovery of various mutations in the tau gene among the families affected by frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) suggests gain-of-toxic function of wild-type or mutant tau as the mechanism for extensive neuronal loss. To learn about the role of tau in the tauopathy, we have generated animal models that express FTDP-17 mutant (P301L or R406W) tau. 1.We established transgenic mice expressing prion promoter-driven P301L mutant tau. The brains were sampled from those mice at various ages (3, 6, 12, 20, and 24 months) and analyzed by either biochemical or immunohistochemical methods. However, transgene-derived alterations, such as degeneration of neurons and deposition of tau, were not observed up to 24 months. 2.We generated transgenic nematode (Caenorhabditis elegans) expressing wild-type or mutant (P301L and R406W) tau in the touch (mechanosensory) neurons. Whereas the worm expressing wild-type tau showed only a small decrease in the touch response across the lifespan, the worm expressing mutant tau displayed a large and progressive decrease. When the touch neurons lost their function, neuritic abnormalities were prominent, and microtubular loss became remarkable in the later stage. A substantial fraction of degenerating neurons developed tau accumulation in the cell body and neuronal processes. This neuronal dysfunction is not related to the apoptotic process because little recovery from touch abnormality was observed in the ced-3 or ced-4-deficient background. Expression of GSK3 brought about slight deterioration in the touch response, while expression of HSP70 led to some improvement., Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, 2000 -2004, Grant-in-Aid for Scientific Research on Priority Areas, University of Tokyo
• 特殊ペプチド化合物によるアミロイドβタンパク質特異的産生抑制法の開発
  JST, 産学共同シーズイノベーション化事業, 公的機関（文部科学省・日本学術振興会を除く)からの各種助成, Competitive research funding
• Aß産生
  上原記念生命科学財団, 上原記念生命科学研究助成金, 各種団体からの研究助成, Competitive research funding
• アルツハイマー病におけるアミロイドβタンパク質産生に関する研究
  財団法人パブリックヘルスリサーチセンター, 研究助成金, 各種団体からの研究助成, Competitive research funding
• ガンマセクレターゼの活性制御因子の探索と制御機構
  若手研究（Ａ）, Competitive research funding
• Production of amyloid beta-protein
  Competitive research funding
• アミロイドβタンパク質の産生機序の解明
  Competitive research funding

Research Seeds

• Anti-Alzheimer's disease peptides

  Research Fields: Medical and Pharmaceutical Sciences