Novel neuroprotective factors against both ALS and Alzheimer's disease and the action mechanism study

• Project/Area Number: 19591007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Keio University
• Principal Investigator: KITA Yoshiko Keio University, 医学部, 講師 (00327496)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ADNF / HN / ALS / アルツハイマー病 / コリベリン / ヒューマニン(HN) / 神経変性疾患 / MND / G93A-SOD1

Research Abstract

抗ALS及び抗アルツハイマー活性を有する神経保護因子コリベリン(ADNF-HN誘導体)の高活性(fM)のメカニズム解明をめざして、構成成分であるADNF、AGAC8R-HNG17と共にキャラクタライゼーションを実施した。CD、分析用超遠心によるキャラクタライゼーションの結果は今までの2量体化説に反し、コリベリン、ADNF、AGAC8R-HNG17とも単量体である事が、CD及び、分析用超遠心の測定から強く示唆された。またターゲット分子の1つとしてFPRL-1が考えられる。

Research Products

• [Journal Article] Active form of Neuroprotective Humanin, HN and inactive analog, S7A-HN, are monomeric and disordered in aqueous phosphatesolution at pH6.0 ; No correlation of solution structure with activity (2009)
  • Author(s): Arisaka F, Arakawa T, Niikura T, Kita Y
  • Journal Title: Protein Pept Lett 16 Pages: 132-137
  • Peer Reviewed
• [Journal Article] Synergistic virus inactivation effects of arginine (2009)
  • Author(s): Arakawa T, Kita Y, Koyama H
  • Journal Title: Biotechnology J 4 Pages: 174-178
  • Peer Reviewed
• [Journal Article] MEP chromatography of antibody and Fc-fusion protein using aqueous arginine solution (2009)
  • Author(s): Arakawa T, Kita Y, Sato H, Ejima D
  • Journal Title: Protein Expt. Purf 63 Pages: 158-163
  • Peer Reviewed
• [Journal Article] Active form of Neuroprotective Humanin, HN, and inactive alalog, S7A-HN, are monomeric and disordered in aqueous phosphate solution at pH6.0 ; No correlation of solution structure with activity (2009)
  • Author(s): Arisaka F, Arakawa T, Niikura T, Kita Y
  • Journal Title: Protein Pept. Lett. 16 Pages: 132-137
  • Peer Reviewed
• [Journal Article] MEP chromatography of antibody and Fc-fusion protein usingaqueous arginie solution (2009)
  • Author(s): Arakawa T, Kita Y, Sato H, Ejima D
  • Journal Title: Protein Expr. Purf. 63 Pages: 158-163
  • Peer Reviewed
• [Journal Article] A rescue factor for Alzheimer's disease : discovery, activity, structure and mechanism (2008)
  • Author(s): Arakawa T, Kita Y, Niikura T
  • Journal Title: Curr. Med. Chem 15 Pages: 2088-2098
  • Peer Reviewed
• [Journal Article] The structure analysis of Humanin analog, AGAC8R-HNG17, by circular dichroism and sedimentation equilibrium : Comparison with the parent molecule (2008)
  • Author(s): Arisaka F, Niikura T, Arakawa T, Kita Y
  • Journal Title: Int. J. Biol. Macromol 43 Pages: 88-93
  • Peer Reviewed
• [Journal Article] The complex structure transition of Humanin peptides by sodium dodecylsulfate and trifluoroethanol (2008)
  • Author(s): Kita Y, Niikura T, Arisaka F, Arakawa T
  • Journal Title: Protein Pept. Lett 15 Pages: 510-515
  • Peer Reviewed
• [Journal Article] Solvent modulation of column chromatography (2008)
  • Author(s): Arakawa T, Kita Y, Ejima D, Gagnon P
  • Journal Title: Protein Pept. Lett 15 Pages: 544-555
  • Peer Reviewed
• [Journal Article] Mammalian Gup1, a homolog of Saccharomyces cerevisiae glycerol uptake/transporter 1, acts as anegative regulator for N-terminal palmitoylation of Sonic hedgehog (2008)
  • Author(s): Abe Y, Kita Y, Niikura T
  • Journal Title: FEBS J 275 Pages: 318-331
  • Peer Reviewed
• [Journal Article] Solubility enhancement of gluten and organic compounds by arginine (2008)
  • Author(s): Arakawa T, Kita Y, Koyama AH
  • Journal Title: Int. J. Pharm 355 Pages: 220-223
  • Peer Reviewed
• [Journal Article] A rescue factor for Alzheimer's disease : discovery, activity, structure, and mechanism (2008)
  • Author(s): Arakawa T, Kita Y, Niikura T
  • Journal Title: Curr. Med. Chem. 15 Pages: 2086-2098
  • Peer Reviewed
• [Journal Article] The sturucture analysis of Humanin analog, AGAC8R-HNG17, by circular dichroism and sedimentation equilibrium : Comparison with the parent molecule (2008)
  • Author(s): Arisaka F, Niikura T, Arakawa T, Kita Y
  • Journal Title: Int. J. Biol. Macromol. 43 Pages: 88-93
  • Peer Reviewed
• [Journal Article] The complex structure transition of Humanin peptides by sodium dodecylsulfate and trifluoroethanol (2008)
  • Author(s): Kita Y, Niikura T, Arisaka F, Arakawa T
  • Journal Title: Protein Pept. Lett. 15 Pages: 510-515
  • Peer Reviewed
• [Journal Article] Mammalian Gup l,ahomolog of Saccharomyces cerevisiae glyceroluptake/transporter 1,acts as a negative regulator for N-terminal palmitoylation of Sonic hedgehog (2008)
  • Author(s): Abe Y, Kita Y, Niikura T
  • Journal Title: FEBS J. 275 Pages: 318-331
  • Peer Reviewed
• [Journal Article] Sollubility enhancement of gluten and organic compounds by arginine (2008)
  • Author(s): Arakawa T, Kita Y, Koyama AH
  • Journal Title: Int J Pharm 355 Pages: 220-223
  • Peer Reviewed
• [Journal Article] Structure analysis of Activity-Dependent Neurotrophic factor 9 by circular dichroism and sedimentation equilibrium (2007)
  • Author(s): Arakawa T, Niikura T, Tajima H, Arisaka F, Kita Y
  • Journal Title: J. Mol. Neurosci 33 Pages: 262-267
  • Peer Reviewed
• [Journal Article] Activity dependentneurotrophic factor ADNF, determined the structure characteristics of Colvelin a fusion protein of ADNF9 and Humanin (2007)
  • Author(s): Arakawa T, Niikura T, Arisaka F, Kita Y
  • Journal Title: J. Pept Sci 14 Pages: 631-636
• [Journal Article] Protein precipitation and denaturation by dimethyl sulfoxide (2007)
  • Author(s): Arakawa T, Kita Y, Timasheff S
  • Journal Title: Biophys Chem 131 Pages: 62-70
  • Peer Reviewed
• [Journal Article] Structure analysis of Activity-Dependent Neurotrophic Factor 9 by circular dichroism and sedimentation equilibium (2007)
  • Author(s): Arakawa T, Niikura T, Tajima H, Arisaka F, Kita Y
  • Journal Title: J.Mol Neurosci 33 Pages: 262-267
  • Peer Reviewed
• [Journal Article] Activity-dependent neurotrophic gactor ADNF, determines the sturucturecharacteristics of Colivelin a fusion protein of ADNF9 and Humaninanalog (2007)
  • Author(s): Arakawa T, Niikura T, Arisaka F, Kita Y
  • Journal Title: J Pept Sci 14 Pages: 631-636
  • Peer Reviewed
• [Journal Article] Protein Precipitation and denaturation by dimethyl sulfoxide (2007)
  • Author(s): Arakawa T, Kita Y, Timasheff S
  • Journal Title: Biophys Chem 131 Pages: 62-70
  • Peer Reviewed
• [Presentation] 結晶構造を基盤としたアルギニン塩酸塩の存在による蛋白質の水和変化の解析(Structure-based analysis reveals hydration changes induced by arginine hydrochloride) (2008)
  • Author(s): 中木戸誠、田中良和、三堀麻理子、工藤基徳、江島大輔、喜多淑子、荒川力、津本浩平
  • Organizer: 第31回日本分子生物学会年会、合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 結晶構造を基盤としたアルギニン塩酸塩の存在による蛋白質の水和変化の解析(structure-based analysis revealshydration changes induced by arginine hydrochloride) (2008)
  • Author(s): 中木戸誠, 田中良和, 三堀麻理子, 工藤基徳, 江島大輔, 喜多淑子, 荒川力, 津本浩平
  • Organizer: 第31回日本分子生物学会年会、第81回日本生物化学会大会、合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] A Structure-Activity relationship of AGAC8R-HNG17, a component of femtomolar acting factor Colivelinagainst Alzheimer's disease insults : Comparison studied of ADNF Humanin(HN)and the analogues (2008)
  • Author(s): Kita Y, Niikura T, Arakawa T Arisaka F
  • Organizer: SFN(Society for Neuroscience)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2008-11-19
• [Presentation] A Structure-Activity relationship of AGAC8R-HNG17, a COmponent of femtomolar acting factor Colivelin aeainst Alzheimer's. disease insults : Comparison studies of ADNF, HumaniD(HN)and the anlogues (2008)
  • Author(s): Kita Y. Niikura T, Arakawa T, Arisaka F
  • Organizer: Neuroscinece 2008, SFN (Society for Neuroscience)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2008-11-19
• [Presentation] Drug candidate for Alzheimer's disease and ALS : Characterization of femto molar acting neuroprotective peptides ADNF and Colivelin, a linking peptide of ADNF and HN defivative (2008)
  • Author(s): Kita Y, Niikura T, Arisaka F, Arakawa T
  • Organizer: Keystone Symposia
  • Place of Presentation: Keystone, Colorado, USA
  • Year and Date: 2008-03-26
• [Presentation] Drug candidate for Alzheimer's disease and ALS:Characterization of femto molar acting neuroprotective peptides ADNF and Colivelin, a linking of ADNF and HN dericative (2008)
  • Author(s): Kita Y, Niikura T, Arisaka F, Arakawa T
  • Organizer: Keystone Symposia
  • Place of Presentation: Keystone,Colorado USA
  • Year and Date: 2008-03-26
• [Presentation] Drug candidate for AD and ALS : structure analysis of femto-molar acting neuroprotective peptides ADNF and Colivelin (2007)
  • Author(s): Kita Y, Niikura T, Tajima H, Arisaka F,Arakawa T
  • Organizer: Neuroscinece 2007, SFN(Society of Neuroscience)
  • Place of Presentation: San Diego, California USA
  • Year and Date: 2007-11-06
• [Presentation] Drug candidate for AD and ALS:structure analysis of femto-molar acting neuroprotective peptides ADNF and Colivelin (2007)
  • Author(s): Kita Y, Niikura T, Tajima H, Arisaka F, Arakawa T
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego,California USA
  • Year and Date: 2007-11-06
• [Presentation] Characterization of femto-molar acting neuroprotective peptides, ADNF and Colivelin : Potential mechanism of their action (2007)
  • Author(s): Kita Y
  • Organizer: Summer Neuropeptide Conference
  • Place of Presentation: Essex Vermont, USA
  • Year and Date: 2007-09-09
• [Presentation] Characterization of femto-molar acting neuroportective peptides,ADNF and Colivehn:Potential mechanism of their action (2007)
  • Author(s): Kita Y
  • Organizer: Summer Neuropeptide Conference
  • Place of Presentation: Essex,Vermont,USA
  • Year and Date: 2007-09-09
• [Remarks]
  • URL: http://web.sc.itc.keio.ac.jp/pharm/achievement/index.html
• [Remarks]
  • URL: http://web.sc.itc.keio.ac.jp/pharm/achievement/index.html