Cellular stress by proteins contaminated with D-serine as a novel therapeutic target of amyotrophic lateral sclerosis

• Project/Area Number: 22790828
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Keio University
• Principal Investigator: SASABE Jumpei 慶應義塾大学, 医学部, 助教 (10398612)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: D-アミノ酸 / D-tyr-tRNA deacylase / D-セリン / 筋萎縮性側索硬化症 / D-Tyr-tRNA deacylase

Research Abstract

We investigated in this study how motoneurons reacts against contamination of D-amino acids in protein synthesis by focusing on D-tyr-tRNA deacylase(DTD). D-amino acids do not make any cellular stresses in the existence of DTD, whereas genetic disruption of DTD enhances unfolded protein response and D-amino acids increase ubiquitinated proteins.

Research Products

• [Journal Article] D-amino acid oxidase controls motoneuron degeneration through D-serine (2012)
  • Author(s): Jumpei Sasabe, Yurika Miyoshi, Masataka Suzuki, Masashi Mita, Ryuichi Konno, Masaaki Matsuoka, Kenji Hamase, Sadakazu Aiso
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Pages: 627-32
  • Peer Reviewed
• [Journal Article] D-Ser-containing humanin shows promotion of fibril formation (2012)
  • Author(s): Kanehiro Hayashi, Jumpei Sasabe, Tomohiro Chiba, Sadakazu Aiso, Naoko Utsunomiya-Tate
  • Journal Title: Amino Acids Volume: (in press)
  • Peer Reviewed
• [Journal Article] D-Amino acid oxidase controls motoneuron degeneration through D-serine (2012)
  • Author(s): Jumpei SASABE, et al
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 109 Issue: 2 Pages: 627-632
  • DOI: 10.1073/pnas.1114639109
  • Peer Reviewed
• [Journal Article] D-Ser-containing humanin shows promotion of fibril formation (2011)
  • Author(s): Hayashi K, Sasabe J, Chiba T, Aiso S, Utsunomiya-Tate N
  • Journal Title: Amino acids Volume: 42 Issue: 6 Pages: 2293
  • DOI: 10.1007/s00726-011-0971-6
  • Peer Reviewed
• [Journal Article] D-Serine in the pathogenesis of amyotrophic lateral sclerosis (2010)
  • Author(s): Jumpei Sasabe, Sadakazu Aiso
  • Journal Title: Seikagaku Volume: 82 Pages: 628-32
• [Journal Article] Aberrant control of motoneuronal excitability in amyotrophic lateral sclerosis : excitatory glutamate/D-serine vs. inhibitory glycine/gamma-aminobutanoic acid(GABA) (2010)
  • Author(s): Jumpei Sasabe, Sadakazu Aiso
  • Journal Title: ChemBiodivers Volume: 7 Pages: 1479-90
  • Peer Reviewed
• [Journal Article] D-serine in the pathogenesis of amyotrophic lateral sclerosis (2010)
  • Author(s): Sasabe J, Aiso S
  • Journal Title: Seikagaku Volume: 82 Pages: 628-632
• [Journal Article] Aberrant control of motoneuronal excitability in amyotrophic lateral sclerosis : excitatory glutamate/D-serine vs.inhibitory glycine/gamma-aminobutanoic acid (GABA) (2010)
  • Author(s): Sasabe J, Aiso S
  • Journal Title: Chem.Biodivers. Volume: 7 Pages: 1479-1490
  • Peer Reviewed
• [Presentation] D-Serine homeostasis in the spinal cord and motoneuron degeneration (2011)
  • Author(s): 笹部潤平
  • Organizer: CBIR international symposium
  • Place of Presentation: 東京
  • Year and Date: 2011-09-10
• [Presentation] 運動神経路におけるD-セリンと運動神経変性 (2011)
  • Author(s): 笹部潤平
  • Organizer: 第7回D-アミノ酸研究会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-10
• [Presentation] 運動神経路におけるD-セリンと運動神経変性 (2011)
  • Author(s): Sasabe J
  • Organizer: D-アミノ酸学会
  • Place of Presentation: 東京医科歯科大学M&Dタワー(東京都)
  • Year and Date: 2011-09-10
• [Presentation] D-Serine homeostasis in the spinal cord and motoneuron degeneration (2011)
  • Author(s): Sasabe J
  • Organizer: CBIR International Symposium
  • Place of Presentation: 東京医科歯科大学M&Dタワー(東京都)(招待講演)
  • Year and Date: 2011-09-10
• [Presentation] Control of D-serine by astrocytic D-amino acid oxidase in descending motor tract (2010)
  • Author(s): Sasabe J
  • Organizer: 北米神経科学会
  • Place of Presentation: サンディエゴ(US)
  • Year and Date: 2010-11-14
• [Presentation] Control of D-serine by astrocytic D-amino acid oxidase in descending motor tract (2010)
  • Author(s): 笹部潤平
  • Organizer: 第6回D-アミノ酸研究会学術講演会
  • Place of Presentation: 富山
  • Year and Date: 2010-09-17
• [Presentation] Control of D-serine by astrocytic D-amino acid oxidase in descending motor tract (2010)
  • Author(s): Sasabe J
  • Organizer: D-アミノ酸学会
  • Place of Presentation: 富山(JPN)
  • Year and Date: 2010-09-17
• [Presentation] Control of D-serine by astrocytic D-amino acid oxidase in descending motor tract (2010)
  • Author(s): 笹部潤平
  • Organizer: 2010 Society for Neuroscience
  • Place of Presentation: サンディエゴ(米国)
• [Book] Annual Review神経 (2012)
  • Author(s): 笹部潤平、相磯貞和
  • Publisher: 中外医学社
• [Book] 「D-セリンと中枢神経機能」Annual Review神経2012 (2012)
  • Author(s): 笹部潤平、相磯貞和
  • Publisher: 中外医学社
• [Book] Clinical Neuroscience (2011)
  • Author(s): 鈴木将貴、笹部潤平
  • Publisher: 中外医学社
• [Book] 「アストロサイトとアミノ酸代謝」Clinical Neuroscience 2011 (2011)
  • Author(s): 鈴木将貴、笹部潤平
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://www.anatomy.med.keio.ac.jp/aiso/
• [Remarks]
  • URL: http://web.sc.itc.keio.ac.jp/anatomy/anatomy.aiso-lab/member.html