Development and use of amyloid secretase modulators in Alzhaimer's disease.

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 13210027
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: ISHIURA Shoichi The University of Tokyo, Professor, 大学院総合文化研究科, 教授 (10158743)
• Project Period (FY): 2001 – 2004
• Keywords: a-Secretase / β-secretase / ADAM / BACE1 / BACE1 inhibitor

Research Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major component of the plaques, amyloid β peptide (Aβ), is generated from amyloid precursor protein (APP) by β-and γ. secretase-mediated cleavages. Since BACE1 (β-site APP cleaving enzyme 1)-knockout mice produce much less Aβand grow healthily without apparent side effects, BACE1 inhibitor is thought to be one of the most attractive targets for the development of therapeutic interventions for AD.
Here, we report in vivo inhibitory effects of a novel BACE1 inhibitor, KMI-429, which is a transition-state mimic, effectively inhibits β- secretase activity in cultured cells in a dose-dependent manner. We injected KMI.429 into the hippocampus of APP transgenic and wild-type mice and measured the release of sAPPβ (soluble extracellular fragment of APP generated by β-secretase), the level of APP-CTF (C-terminal fragment of APP) and Aβ level by quantitative Western blotting and sandwitch ELISA. KMI.429 significantly reduced Aβ production in soluble fraction compared with vehicle in vivo, but changes in Aβ levels in insoluble fraction were not so affected. In contrast, the intrahippocampal injection of KMI.429 in wild-type mice remarkably reduced Aβ production in both soluble and insoluble fractions. Our results indicate that the BACE1 inhibitor KMI.429 would be a promising candidate for a treatment for AD.

Research Products

• [Journal Article] Independent accumulations of tau and amyloid b protein in the human entorhinal cortex. (2005)
  • Author(s): Katsuno, T., Morishima-Kawashima, M., Saito, Y., Yamanouchi, H., Ishiura, S., Muyarama, S., Ihara, Y.
  • Journal Title: Neurology 64 Pages: 687-692
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification and characterization of Hesr1/Hey1 as a candidate trans-acting factor on gene expression through the 3' non-coding polymorphic region of the human dopamine transporter (DAT1) gene. (2005)
  • Author(s): Fuke, S., Sasagawa, N., Ishiura, S.
  • Journal Title: J.Biochem. 137 Pages: 205-216
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Comparative analysis of the cytotoxicity of homopolymeric amino acids. (2005)
  • Author(s): Oma, Y., Kino, Y., Sasagawa, N., Ishiura, S.
  • Journal Title: Biochim.Biophys.Acta 1748 Pages: 174-179
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Denervation enhances the expression of SHPS-1 in the rat skeletal muscle. (2005)
  • Author(s): Mitsuhashi, H., Yoshikawa, A., Sasagawa, N., Hayashi, Y., Ishiura, S.
  • Journal Title: J.Biochem. 137 Pages: 495-502
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterization of a novel D2-like dopamine receptor with a truncated splice variant and a D1-like dopamine receptor unique to invertebrates from Caenorhabditis elegans. (2005)
  • Author(s): Sugiura, M., Fuke, S., Suo, S., Sasagawa, N., Van Tol, H.H.M., Ishiura, S.
  • Journal Title: J.Neurochem. 94(in press) Pages: 1146-1157
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Independent accumulations of tau and amyloid β protein in the human entorhinal cortex. (2005)
  • Author(s): Katsuno, T., Morishima-Kawashima, M., Saito, Y., Yamanouchi, H., Ishiura, S., Muyarama, S., Ihara, Y.
  • Journal Title: Neurology 64 Pages: 687-692
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification and characterization of Hesrl/Hey1 as a candidate trans-acting factor on gene expression through the 3' non-coding polymorphic region of the human dopamine transporter (DAT1) gene. (2005)
  • Author(s): Fuke, S., Sasagawa, N.Ishiura, S.
  • Journal Title: J.Biochem. 137 Pages: 205-216
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Comparative analysis of the cytotoxicity of homopolymeric amino acids. (2005)
  • Author(s): Oma, Y., Kino, Y., Sasagawa, N.Ishiura, S.
  • Journal Title: Biochim.Biophys.Acta 1748 Pages: 174-179
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Denervation enhances the expression of SHPS-1 in the rat skeletal muscle. (2005)
  • Author(s): Mitsuhashi, H., Yoshikawa, A., Sasagawa, N., Hayashi, Y.Ishiura, S.
  • Journal Title: J.Biochem. 137 Pages: 495-502
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization of a novel D2-like dopamine receptor with a truncated splice variant and a D1-like dopamine receptor unique to invertebrates from Caenorhabditis elegans. (2005)
  • Author(s): Sugiura, M., Fuke, S., Suo, S., Sasagawa, N., Van Tol, H.H.M.Ishiura, S.
  • Journal Title: J.Neurochem. 94 Pages: 1146-1157
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mammalian D-aspartyl endopeptidase : a scavenger for noxious racemized proteins in aging. (2004)
  • Author(s): Kinouchi, T., Ishiura, S., Mabuchi, Y., Urakami-Manaka, Y., Nishio, H., Nishiuchi, Y., Tsunemi, M., Takeda K., Watanabe, M., Ikeda, M., Matsui, H., Tomioka, S., Kawahara, H., Hamamoto, T., Suzuki.K., Kagawa, Y.
  • Journal Title: Biochem.Biophys.Res.Commun 314 Pages: 730-736
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] ADAMs, a disintegrin metalloproteinases, mediate shedding of oxytocinase. (2004)
  • Author(s): Ito, N., Nomura, S., Iwase, A., Ito, T., Kikkawa, F., Tsujimoto, M., Ishiura, S., Mizutani, S.
  • Journal Title: J.Biochem. 314 Pages: 1008-1013
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats. (2004)
  • Author(s): Kino, Y., Oma, Y., Sasagawa, N., Ishiura, S.
  • Journal Title: Human Mol.Genet. 13 Pages: 495-507
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] KMI-358 and KMI-370, highly potent and small-sized BACE1 inhibitors containing phenylnorstatine. (2004)
  • Author(s): Kimura.T., Shuto, D., Kasai, S., Liu, P., Hidaka, K., Hamada, T., Hayashi, Y., Hattori, C., Asai, M., Kitazume, S., Saido, T.C., Ishiura, S., Kiso, Y.
  • Journal Title: Bioorg. Med. Chem. Lett. 14 Pages: 1527-1531
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Intracellular localization of homopolymeric amino acid-containing proteins expressed in mammalian cells. (2004)
  • Author(s): Oma, Y., Kino, Y., Sasagawa, N., Ishiura S.
  • Journal Title: J.Biol.Chem. 278 Pages: 21217-21222
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of amyloid-bl-40 and 1-42 peptides in Capsicum annum var. angulosum for oral immunization. (2004)
  • Author(s): Szabo, B., Hori, K., Nakajima, A., Sasagawa, N., Watanabe, Y., Ishiura, S.
  • Journal Title: ASSAY and Drug Development Technologies 2 Pages: 383-388
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] BDopamine receptors in C.elegans. (2004)
  • Author(s): Suo, S., Ishiura, S., Van Tol, H.H.M.
  • Journal Title: Eur.J.Pharmacol. 500 Pages: 159-166
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mammalian D-aspartyl endopeptidase : a scavenger for noxious racemized proteins in aging. (2004)
  • Author(s): Kinouchi, T., Ishiura, S., Mabuchi, Y., Urakami-Manaka, Y., Nishio, H., Nishiuchi, Y., Tsunemi, M., Takeda, K., Watanabe, M., Ikeda, M., Matsui, H., Tomioka, S., Kawahara, H., Hamamoto, T., Suzuki, K, Kagawa, Y.
  • Journal Title: Biochem.Biophys.Res.Commun. 314 Pages: 730-736
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] ADAMs, a disintegrin metalloproteinases, mediate shedding of oxytocinase. (2004)
  • Author(s): Ito, N., Nomura, S., Iwase, A., Ito, T., Kikkawa, F., Tsujimoto, M., Ishiura, S.Mizutani, S.
  • Journal Title: Biochem.Biophys.Res.Commun. 314 Pages: 1008-1013
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats. (2004)
  • Author(s): Kino, Y., Oma, Y., Sasagawa, N.Ishiura, S.
  • Journal Title: Human Mol.Genet. 13 Pages: 495-507
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] KMI-358 and KMI-370, highly potent and small-sized BACE 1 inhibitors containing phenylnorstatine. (2004)
  • Author(s): Kimura, T., Shuto, D., Kasai, S., Liu, P., Hidaka, K., Hamada, T., Hayashi, Y., Hattori, C., Asai, M., Kitazume, S., Saido, T.C., Ishiura, S.Kiso, Y.
  • Journal Title: Bioorg.Med.Chem.Lett. 14 Pages: 1527-1531
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Intracellular localization of homopolymeric amino acid-containing proteins expressed in mammalian cells. (2004)
  • Author(s): Oma, Y., Kino, Y., Sasagawa, N.Ishiura S.
  • Journal Title: J.Biol.Chem. 279 Pages: 21217-21222
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of amyloid-β1-40 and 1-42 peptides in Capsicum annum var. angulosum for oral immunization. (2004)
  • Author(s): Szabo, B., Hori, K., Nakajima, A., Sasagawa, N., Watanabe, Y.Ishiura, S.
  • Journal Title: ASSAY and Drug Development Technologies. 2 Pages: 383-388
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Dopamine receptors in C.elegans. (2004)
  • Author(s): Suo, S., Ishiura, S., Van Tol, H.H.M.
  • Journal Title: Eur.J.Pharmacol. 500 Pages: 159-166
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Putative function of ADAM9, ADAM10, and ADAM17 as APP a-secretase. (2003)
  • Author(s): Asai, M., Hattori, C., Szabo, B., Sasagawa, N., Maruyama, K., Tanuma, S., Ishiura, S.
  • Journal Title: Biochem.Biophys.Res.Commun. 301 Pages: 231-235
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of ARPP-16/19 in rat denervated skeletal muscle. (2003)
  • Author(s): Yoshikawa, A., Mitsuhashi, H., Sasagawa, N., Tsukahara, T., Hayashi, Y., Nishino, I., Goto, Y., Ishiura, S.
  • Journal Title: J.Biochem. 134 Pages: 57-61
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Potential link between amyloid beta protein 42 and C-terminal fragment gamma49-99 of beta amyloid precursor protein. (2003)
  • Author(s): Sato, T., Dohmae, N., Qi, Y., Misonou H., Mitsumori, R., Maruyama H., Koo, E.H., Haass, C., Takio, K., Morishima-Kawashima M., Ishiura S., Ihara Y.
  • Journal Title: J.Biol.Chem. 278 Pages: 24294-24301
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cloning and characterization of a C. elegans D2-like dopamine receptor. (2003)
  • Author(s): Suo, S., Sasagawa, N., Ishiura, S.
  • Journal Title: J.Neurochem. 86 Pages: 869-878
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] KMI-008, a novel beta-secretase inhibitor containing a hydroxymethylcarbonyl isostere as a transition-state mimic : Design and synthesis of substrate-based octapeptides. (2003)
  • Author(s): Shuto, D., Kasai, S., Kimura T., Liu, P., Hidaka, K., Hamada T., Shibakawa, S., Hayashi, Y., Hattori.C., Szabo, B., Ishiura S., Kiso, Y.
  • Journal Title: Bioorg. Med. Chem. Lett. 13 Pages: 4273-4276
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Putative function of ADAM9, ADAM 10, and ADAM 17 as APP a-secretase. (2003)
  • Author(s): Asai, M., Hattori, C., Szabo, B., Sasagawa, N., Maruyama, K., Tanuma, S., Ishiura, S.
  • Journal Title: Biochem.Biophys.Res.Commun. 301 Pages: 231-235
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Potential link between amyloid beta protein 42 and C-terminal fragment gamma49-99 of beta amyloid precursor protein. (2003)
  • Author(s): Sato, T., Dohmae, N., Qi, Y., Misonou, H., Mitsumori, R., Maruyama, H., Koo, E.H., Haass, C., Takio, K., Morishima-Kawashima, M, Ishiura, S., Ihara, Y.
  • Journal Title: J.Biol.Chem. 278 Pages: 24294-24301
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] KMI-008, a novel beta-secretase inhibitor containing a hydroxymethylcarbonyl isostere as a transition-state mimic : Design and synthesis of substrate-based octapeptides. (2003)
  • Author(s): Shuto, D., Kasai, S., Kimura, T., Liu, P., Hidaka, K., Hamada, T., Shibakawa, S., Hayashi, Y., Hattori, C., Szabo, B., Ishiura S., Kiso, Y.
  • Journal Title: Bioorg.Med.Chem.Lett. 13 Pages: 4273-4276
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of a dopamine receptor from Caenohabditis elegans. (2002)
  • Author(s): Suo, S., Sasagawa, N., Ishiura, S.
  • Journal Title: Neurosci.Lett. 319 Pages: 13-16
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The first molecular evidence that autophagy relates rimmed vacuole formation in chloroquine myopathy. (2002)
  • Author(s): Suzuki, T., Nakagawa, M., Yoshikawa, A., Sasagawa, N., Yoshimori, T., Ohsumi, Y., Nishsino, I., Ishiura, S., Nonaka, I.
  • Journal Title: J.Biochem. 131 Pages: 647-651
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A secreted form of ADAM9 has an a-secretase activity for APP. (2002)
  • Author(s): Hotoda, N., Koike, H., Sasagawa, N., Ishiura, S.
  • Journal Title: Biochem.Biophys.Res. Commun. 293 Pages: 800-805
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] BACE1 interacts with nicastrin. (2002)
  • Author(s): Hattori, C., Asai, M., Oma, Y., Kino, Y., Sasagawa, N., Saido, T.C., Mariyama, K., Ishiura, S.
  • Journal Title: Biochem.Biophys.Res.Commun. 293 Pages: 1228-1232
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of a dopamine receptor from Caenohabditis elegans. (2002)
  • Author(s): Suo, S., Sasagawa, N.Ishiura, S.
  • Journal Title: Neurosci.Lett. 319 Pages: 13-16
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The first molecular evidence that autophagy relates rimmed vacuole formation in chloroquine myopathy. (2002)
  • Author(s): Suzuki, T., Nakagawa, M., Yoshikawa, A., Sasagawa, N., Yoshimori, T., Ohsumi, Y., Nishsino, I., Ishiura, S.Nonaka, I.
  • Journal Title: J.Biochem. 131 Pages: 647-651
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A secreted form of ADAM9 has an a-secretase activity for APP. (2002)
  • Author(s): Hotoda, N., Koike, H., Sasagawa, N., Ishiura, S.
  • Journal Title: Biochem.Biophys.Res.Commun. 293 Pages: 800-805
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] BACE 1 interacts with nicastrin. (2002)
  • Author(s): Hattori, C., Asai, M., Oma, Y., Kino, Y., Sasagawa, N., Saido, T.C., Mariyama, K., Ishiura, S.
  • Journal Title: Biochem.Biophys.Res.Commun. 293 Pages: 1228-1232
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression. (2001)
  • Author(s): Fuke, S., Suo, S., Takahashi, N., Koike, H., Sasagawa, N., Ishiura, S.
  • Journal Title: The Pharmacogenomics J. 1 Pages: 152-156
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Limited proteolysis of filamin is catalyzed by caspase-3 in U937 and Jurkat cells. (2001)
  • Author(s): Umeda T, Kouchi Z, Kawahara H, Tomioka S, Sasagawa N, Maeda T, Sorimachi H, Ishiura S, Suzuki K
  • Journal Title: J.Biochem. 130 Pages: 535-542
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alzheimer amyloid α-secretase : a special target for drug development. (2001)
  • Author(s): Ishiura, S., Hotoda, N., Szabo, B., Asai, M., Hattori, C., Tanaka, E., Koike, H., Sasagawa, N.
  • Journal Title: Psychogeriatrics 1 Pages: 273-276
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Limited proteolysis of filamin is catalyzed by caspase-3 in U937 and Jurkat cells. (2001)
  • Author(s): Umeda T, Kouchi Z, Kawahara H, Tomioka S, Sasagawa N, Maeda T, Sorimachi H, Ishiura S, Suzuki K.
  • Journal Title: J.Biochem. 130 Pages: 535-542
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alzheimer amyloid α.secretase : a special target for drug development. (2001)
  • Author(s): Ishiura, S., Hotoda, N., Szabo, B., Asai, M., Hattori, C., Tanaka, E., Koike, H.Sasagawa, N.
  • Journal Title: Psychogeriatrics 1 Pages: 273-276
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Molecular interactions between presenilin and calpain : inhibition of m-calpain protease activity by presenilin-1, 2 and cleavage of presenilin-1 by m-, μ-calpain. (2000)
  • Author(s): Maruyama, K., Usami, M., Kametani, F., Tomita, T., Iwatsubo, T., Saido, T.C., Mori, H, Ishiura, S.
  • Journal Title: Int.J.Mol.Med. 5 Pages: 269-273
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Metabolism of amvloid precursor protein in COS cells transfected with a β-secretase candidate. (2000)
  • Author(s): Koike, H., Kouchi, Z., Kinouchi, T., Maeda, T., Sorimachi, H., Saido.T.C., Maruyama, K., Okuyama, A., Suzuki, K., Ishiura, S.
  • Journal Title: Cytotechnology 33 Pages: 213-219
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Myopathy phenotype of transgenic mice expressing active site-mutated inactive p94 skeletal muscle-specific calpain, the gene product responsible for limb girdle muscular dystrophy type 2A. (2000)
  • Author(s): Tagawa, K., Tgya, C., Hayashi, Y., Nakagawa, M., Ono, Y., Fukuda, R., Karasuyama, H., Toyama-Sorimachi, N., Katsui, Y., Hata S., Ishiura S., Nonaka, I., Seyama Y., Arahata, K., Yonekawa.H., Sorimachi, H., Suzuki, K.
  • Journal Title: Human Mol.Genet 9 Pages: 1393-1402
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Molecular interactions between presenilin and calpain : inhibition of m-calpain protease activity by presenilin-1, 2 and cleavage of presenilin-1 by m-, μ-calpain. (2000)
  • Author(s): Maruyama, K., Usami, M., Kametani, F., Tomita, T., Iwatsubo, T., Saido, T.C., Mori, H., Ishiura, S.
  • Journal Title: Int.J.Mol.Med. 5 Pages: 269-273
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Metabolism of amyloid precursor protein in COS cells transfected with a β-secretase candidate. (2000)
  • Author(s): Koike, H., Kouchi, Z., Kinouchi, T., Maeda, T., Sorimachi, H., Saido.T.C., Maruyama, K., Okuyama, A., Suzuki, K., Ishiura, S.
  • Journal Title: Cytotechnology 33 Pages: 213-219
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Myopathy phenotype of transgenic mice expressing active site-mutated inactive p94 skeletal muscle-specific calpain, the gene product responsible for limb girdle muscular dystrophy type 2A. (2000)
  • Author(s): Tagawa, K., Taya, C., Hayashi, Y., Nakagawa, M., Ono, Y., Fukuda, R., Karasuyama, H., Toyama-Sorimachi, N., Katsui, Y., Hata, S., Ishiura, S., Nonaka, I., Seyama, Y., Arahata, K., Yonekawa, H., Sorimachi, H., Suzuki, K.
  • Journal Title: Human Mol.Genet. 9 Pages: 1393-1402
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] ADAM9. In Proteases in Biology and Disease, volume 4, The ADAM Family of Proteases. (eds. Hooper, Lendeckel)(Kluwer Plenum) (2005)
  • Author(s): Ishiura, S.
  • Total Pages: 344
  • Publisher: New York(in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Book] APP α-secretase, a novel target for Alzheimer drug therapy. In Ab metabolism and Alzheimer's Disease (T.C.Saido. ed.) (2003)
  • Author(s): Ishiura, S., Asai, M., Hattori, C., Hotoda, N., Szabo.B., Sasagawa, N., Tanuma, S.
  • Total Pages: 165
  • Publisher: Eurekah Press
  • Description: 「研究成果報告書概要(和文)」より
• [Book] PP α-secretase, a novel target for Alzheimer drug therapy. in Aβ metabolism and Alzheimer's Disease (T.C. Saido, ed.) (2003)
  • Author(s): Ishiura, S., Asai, M., Hattori, C., Hotoda, N., Szabo.B., Sasagawa, N., Tanuma, S.
  • Total Pages: 23-32
  • Publisher: Eurekah Press
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] ADAM9. In Proteases in Biology and Disease, volume 4, The ADAM Family of Proteases. (eds. Hooper, Lendeckel) Kluwer Plenum,
  • Author(s): Ishiura, S.
  • Publisher: New York (in press)
  • Description: 「研究成果報告書概要(欧文)」より