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糖、アミノ酸等の私たちの体の中に存在し、必要な小さい(低分子=分子量が数百以下のもの)化合物や、種々の薬剤はどのようにして、私たちの健康を守り、疾患を治していくのでしょうか?また、逆に病気を進行させるするものもあります。
これら生理活性低分子化合物の作用機序にはまだよくわかっていないものが多いのですが、前述の低分子化合物の私たちの体の中の標的因子を見つけていこうとしています。すでにいくつか新しく発見したものもあり、その標的因子の遺伝子変異が遺伝病と結びついた例も複数見つかりました。
これらの知見に基づいた新しい治療薬の開発を目指しています。病気等を進行させる標的因子タンパク質の分解(壊す)を誘導するまったく新しい形の薬剤です。
今井剛(いまい たけし)
国立研究開発法人 国立長寿医療研究センター ジェロサイエンス研究センター ケミカルバイオロジー研究部
不撓不屈
Cho J, Miyagawa A, Yamaguchi K, Abe W, Tsugawa Y, Yamamura H, and Imai T*. UDP-glucose, cereblon-dependent proinsulin degrader. Scientific Reports vol 12, Article number: 14568 (2022) IF=4.996.
https://www.nature.com/articles/s41598-022-18902-5 PMCID: PMC9418190 PMID: 36028536
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9418190/
Cho J, Miyagawa A, Yamaguchi K, Abe W, Tsugawa Y, Yamamura H and Imai T*. UDP-Glucose: A Cereblon-Dependent Glucokinase Protein Degrader. Int. J. Mol. Sci. 2022, 23(16), 9094; IF=6.208
https://doi.org/10.3390/ijms23169094.IF=6.208.
https://www.mdpi.com/1422-0067/23/16/9094. PMCID: PMC9409010 PMID: 36012359
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409010/
Cho J, Tsugawa Y, and Imai T*. R1526 residue in arginine/proinsulin binding domain of UGGT1 is involved in proinsulin binding. Biochemical and Biophysical Research Communications, 615: 131-135, IF3.575 (2022). PMID: 32423812, PMCID: PMC7863631, NIHMSID: NIHMS1661560, DOI: 10.1016/j.bbrc.2022.05.060.
https://www.sciencedirect.com/science/article/abs/pii/S0006291X22007653
Cho J, Tsugwa Y, Imai Y, Imai T*. Chorionic gonadotropin stimulates maternal hepatocyte proliferation during pregnancy. Biochemical and Biophysical Research Communications, 579: 110-115, IF3.575 (2021)., PMID:34597993, PMCID: PMC8568302 DOI:10.1016/j.bbrc.2021.09.039
Cho J, Horikawa Y, Enya M, Takeda J, Imai Y, Imai Y, Handa H, Imai T*. L-Arginine prevents cereblon-mediated ubiquitination of glucokinase and stimulates glucose-6-phosphate production in pancreatic β-cells. Communications Biology volume 3, Article number: 497 (2020), DOI: 10.1038/s42003-020-01226-3.
https://www.nature.com/articles/s42003-020-01226-3
Cho J, Hiramoto M, Masaike Y, Sakamoto S, Imai Y, ImaiY, Handa H, Imai T*. UGGT1 retains proinsulin in the endoplasmic reticulum in an arginine dependent manner. Biochem Biophys Res Commun 527(3):668-675, 2020. doi: 10.1016/j.bbrc.2020.04.158
Tsugawa Y, Natori M, Handa H, and Imai T*. Estradiol accelerates liver regeneration through estrogen receptor α. Clinical and Experimental Gastroenterology Volume12, 331-336, 2019. DOI: 10.2147/CEG.S214196
Tsugawa Y, Handa H, and Imai T*. Arginine induces IGF-1 secretion from the endoplasmic reticulum. Biochem Biophys Res Commun Volume 514 (4), 1128-1132 2019. DOI: 10.1016/j.bbrc.2019.05.044
Ando H, Sato T, Ito T, Yamamoto J, Sakamoto S, Nitta N, Asatsuma T, Shimizu N, Mizushima R, Aoki I, Imai T, Yamaguchi Y, Berk AJ, Handa H. Cereblon control of zebrafish brain size by regulation of neural stem cell proliferation. iScience 15, 95-108, 2019. PMID: 31055217. DOI: 10.1016/j.isci.2019.04.007
Tsugawa Y, Hiramoto M, Imai T*. Estrogen induces Estrogen Receptor α expression and hepatocyte proliferation in the late pregnancy. Biochem Biophys Res Commun 511 (3), 592-596, 2019.
Umeda M, Hiramoto M, Watanabe A, Tsunoda N, Imai T*. Arginine-induced insulin secretion in endoplasmic reticulum. Biochem Biophys Res Commun 466(4):717-722, 2015.
Umeda M, Hiramoto M & Imai T*. Partial hepatectomy induces delayed hepatocyte proliferation and normal liver regeneration in ovariectomized mice. Clinical and Experimental Gastroenterology 2015 (8):175-182, 2015, PMCID: PMC4494181.
Uebi T, Umeda M & Imai T*. Estrogen induces Estrogen Receptor alpha expression and hepatocyte proliferation in the livers of the male mice. Genes to Cells 20(3):217-223, 2015. DOI: 10.1111/gtc.12214
Umeda M, Uebi T, Maekawa N, Handa H & Imai T*. PGJIFs, new mitochondrial PGJ2 target proteins, regulate cell proliferation. J Biosciences & Medicines 1 (3):11-15, 2013. DOI: 10.4236/jbm.2013.13003
Umeda M, Uebi T, Maekawa N, Isaki M, Miyama Y, Masaike Y, Handa H & Imai T*. Effective Cofactor Complex Purification using Nanobeads. J Biosciences & Medicines 1 (3):5-10, 2013. DOI: 10.4236/jbm.2013.13002
Uebi T, Umeda M, Maekawa N, Karasawa S, Handa H & Imai T*. Prohibitins, novel vitamin K2 target factors in osteoblast. J Biosciences & Medicines, 1 (3):1-4, 2013. DOI: 10.4236/jbm.2013.13001
Enomoto T, Kawano M, Fukuda H, Sawada W, Inoue T, Haw K, Kita Y, Sakamoto S, Yamaguchi Y, Imai T, Hatakeyama M, Saito S, Sandhu A, Matsui M, Aoki I, Handa H. Viral Protein-Coated Magnetic Nanoparticles for in vivo Tumor-Targeting MR Imaging. J Biotechnol 167 (1):8-15, 2013. DOI:10.1016/j.jbiotec.2013.06.005
Imai T*. Adipogenesis and osteoblastgenesis in aging. Adipocyte: signaling pathways, molecular regulation and impact on human disease. pp95-108. Nova Science Publishers Inc, New York.
Tange S, Zhou Y, Nagakui-Noguchi Y, Imai T & Nakanishi A. Initiation of human astrovirus type 1 infection was blocked by inhibitors of phosphoinositide 3-kinase. Virol J 10:153-166, 2013
Hotta K, Nashimoto A, Yasumura E, Suzuki M, Azuma M, Shima D, Nabeshima R, Hiramoto M, Okada A, Sakata-Sogawa K, Tokunaga M, Ito T, Sakamoto S, Kabe Y, Aizawa S, Imai T, Yamaguchi Y, Watanabe H & Handa H. Vesnarinone suppresses TNFa mRNA expression by inhibiting valosin-containing proteins. Mol Pharm 83(5):930-938, 2013. PMID: 23393163 DOI: 10.1124/mol.112.081935
Karasawa S, Azuma M, Kasama T, Sakamoto S, Kabe Y, Imai T, Yamaguchi Y, Miyazawa K & Handa H. Vitamin K2 covalently binds to Bak and induces Bak-mediated apoptosis. Mol Pharm 83 (3):613-620, 2013. PMID: 23229512 DOI: 10.1124/mol.112.082602
Tange S, Imai T, Nakanishi A. An SV40 mutant defective in VP4 expression exhibits a temperature-sensitive growth defect. Virus Res 157 (1):116-120, 2011.DOI: 10.1016/j.virusres.2011.02.001
Maekawa N, Hiramoto M, Sakamoto S, Ikeda M, Naitou M, Acharya HP, Kobayashi Y, Suematsu M, Handa H & Imai T*. High performance affinity chromatography method for identification of 15-deoxy-Δ12,14-prostaglandin J2 interacting factors using magnetic nanobeads. Biomed Chromatogr 25 (4):466-471, 2011. DOI: 10.1002/bmc.1469
今井剛、西永正典、中村知子、奥宮清人,松林公蔵、土居義典、松下健二. 高齢者住民における保有歯数と認知機能Association with the lipid and sugar metabolism parameters, the number of teeth and cognitive function in elderly population. 愛知学院大学歯学会誌 第48巻59-66ページ2010年
Hiramoto M, Maekawa N, Masaike Y, Kuge T, Ayabe F, Watanabe A, Masaike Y, Hatakeyama M, Handa H & Imai T*. High-performance affinity chromatography method for identification of L-arginine interacting factors using magnetic nanobeads. Biomed Chromatogr 24 (6):606-612, 2010. PMID 19810004
今井剛、西永正典、松下健二. 高齢者の残存歯数と認知機能との関連性. 鹿児島大学医学雑誌 第61巻47-51ページ2010年
Chapellier B, Maekawa N, Hiramoto M, Imai T & Nakanishi A. Cell-type restricted gene delivery using polyomaviral vectors. J Gene Med 11:1156, 2009.
Nakanishi A, Chapellier B, Maekawa N, Hiramoto M, Kuge T, Takahashi RU, Handa H & Imai T. SV40 vectors carrying minimal sequence of the viral origin with exchangeable capsid. Virology 379:110-117, 2008. PMID 18667220
Takahashi RU, Kanesashi SN, Inoue T, Enomoto T, Kawano MA, Tsukamoto H, Takeshita F, Imai T, Ochiya T, Kataoka K, Yamaguchi Y & Handa H. Presentation of functional foreign peptides on the surface of SV40 virus-like particles. J Biotechnol 135:385-392, 2008. PMID 18588926
Inoue T, Kawano MA, Takahashi RU, Tsukamoto H, Enomoto T, Imai T, Kataoka K & Handa H. Engineering of SV40-based nano-capsules for delivery of heterologous protein as fusions with the minor capsid proteins VP2/3. J Biotechnol 134:181-192, 2008. PMID 18243389
Tsukamoto H, Kawano M, Inoue T, Enomoto T, Takahashi R, Yokoyama N, Yamamoto N, Imai T, Kataoka K, Yamaguchi Y & Handa H. Evidence that SV40 VP1-DNA interactions contribute to the assembly of 40-nm spherical viral particles. Genes to Cell 12:1267-1279, 2007. (IF 3.299) PMID 17986010
Yokoyama N, Kawano MA, Tsukamoto H, Enomoto T, Inoue T, Takahashi R, Nakanishi A, Imai T, Wada T & Handa H. Mutational analysis of the carboxyl-terminal region of the SV40 major capsid protein VP1. J Biochem 141:279-286, 2007. PMID 17283011
今井剛. 健康寿命の延伸. 慶應医学、84、149−155、2007
Kawano MA, Inoue T, Tsukamoto H, Takaya T, Enomoto T, Takahashi R, Yokoyama N, Yamamoto N, Nakanishi A, Imai T, Wada T, Kataoka K & Handa H. The VP2/VP3 minor capsid protein of SV40 promotes the in vitro assembly of the major capsid protein VP1 into particles. J Biol Chem 281:10164-10173, 2006. PMID 16478732
今井剛. 老化制御. 医療、60、29—32、2006