教育・研究活動教員紹介

久保山 友晴

久保山 友晴KUBOYAMA Tomoharu

薬学部 漢方薬学科/生薬学分野

  • 学位

    博士(薬学)

  • 所属学会

    日本神経化学会、日本神経科学会、和漢医薬学会、日本生薬学会、日本薬学会、日本薬理学会

  • 専門分野

    神経科学、生薬学、薬理学

  • 研究テーマ

    ・薬剤抵抗性不安障害モデルマウスの開発
    ・神経回路網の再構築による難治性神経疾患(アルツハイマー病、不安障害など)の治療法の開発
    ・作用細胞、作用機序が異なる生薬を組み合わせることによる難治性神経疾患を治療できる漢方方剤の開発

業績

  • (原著論文)
    1. Nakano A., Yang X., Kuboyama T., Inada Y., Tohda C. Intrathecal infusion of diosgenin during the chronic phase of spinal cord injury ameliorates motor function and axonal density. Neurochemical Journal, 15, 454-461, 2021.

    2. Farid MM, Nagasea T, Yang X, Nomoto N, Kuboyama T, Inada Y, Tohda C. Effects of Trigonella foenum-graecum seeds extract on Alzheimer’s disease transgenic model mouse and its potential active compound transferred to the brain. Japanese Journal of Food Chemistry and Safety, 28, 63-70, 2021.

    3. Kuboyama T, Kominato S, Nagumo M, Tohda C. Recovery from spinal cord injury via M2 microglial polarization induced by Polygalae Radix. Phytomedicine, 82:153452, 2021.

    4. Farid MM, Yang X, Kuboyama T, Tohda C. Trigonelline recovers memory function in Alzheimer’s disease model mice: evidence of brain penetration and target molecule. Scientific Reports, 10(1):16424, 2020.

    5. Tanie Y, Kuboyama T, Tohda C. GRP78-Mediated Signaling Contributes to Axonal Growth Resulting in Motor Function Recovery in Spinal Cord-Injured Mice. Frontiers in Pharmacology, 11:789, 2020.

    6. Tohda C, Matsui M, Inada Y, Yang X, Kuboyama T, Kimbara Y, Watari H. Combined Treatment with Two Water Extracts of Eleutherococcus senticosus Leaf and Rhizome of Drynaria fortunei Enhances Cognitive Function: A Placebo-Controlled, Randomized, Double-Blind Study in Healthy Adults. Nutrients, 12, 303, 2020.

    7. Tanabe N, Kuboyama T, Tohda C. Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury. Neural Regeneration Research, 14(11), 1961-1967, 2019.

    8. Yang Z, Kuboyama T, Tohda C. Naringenin promotes microglial M2 polarization and Aβ degradation enzyme expression. Phytotherapy Research, 33(4), 1114–1121, 2019.

    9. Kuboyama T. Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons. Journal of Visualized Experiments, 140: e58229, 2018. https://www.jove.com/embed/directions/58229?key=3nhbpm7t

    10. Tanie Y, Tanabe N, Kuboyama T, Tohda C. Extracellular Neuroleukin Enhances Neuroleukin Secretion From Astrocytes and Promotes Axonal Growth in vitro and in vivo. Frontiers in Pharmacology, 9:1228, 2018.

    11. Tanabe N, Kuboyama T, Tohda C. Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice. Frontiers in Pharmacology, 9:446, 2018.

    12. Kuboyama T, Hirotsu K, Arai T, Yamasaki H, Tohda C. Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease. Frontiers in Pharmacology, 8:805, 2017.

    13. Kuboyama T, Wahane S, Huang Y, Zhou X, Wong JK, Koemeter-Cox A, Martini M, Friedel RH, Zou H. HDAC3 inhibition ameliorates spinal cord injury by immunomodulation. Scientific Reports, 7(1):8641, 2017.

    14. Yang Z., Kuboyama T., Tohda C.: A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule. Frontiers in Pharmacology, 8: 340, 2017.

    15. Tanabe N, Kuboyama T, Kazuma K, Konno K, Tohda C. The extract of roots of Sophora flavescens enhances the recovery of motor function by axonal growth in mice with a spinal cord injury. Frontiers in Pharmacology, 6:326, 2016.

    16. Yang ZY, Kuboyama T, Kazuma K, Konno K, Tohda C. Active Constituents from Drynaria fortunei Rhizomes on the Attenuation of Aβ25-35-Induced Axonal Atrophy. Journal of Natural Products, 78(9):2297-2300, 2015.

    17. Shigyo M, Kuboyama T, Sawai Y, Tada-Umezaki M, Tohda C. Extracellular vimentin interacts with insulin-like growth factor 1 receptor to promote axonal growth. Scientific Reports, 5:12055, 2015.

    18. Kuboyama T, Lee YA, Nishiko H, Tohda C. Inhibition of clathrin-mediated endocytosis prevents amyloid β-induced axonal damage. Neurobiology of Aging, 36(5):1808-1819, 2015.

    19. Watari H, Shigyo M, Tanabe N, Tohda M, Cho KH, Kyung PS, Jung WS, Shimada Y, Shibahara N, Kuboyama T, Tohda C. Comparing the Effects of Kamikihito in Japan and Kami-Guibi-Tang in Korea on Memory Enhancement: Working Towards the Development of a Global Study. Phytotherapy Research, 29(3):351-356, 2015.

    20. Shigyo M, Tanabe N, Kuboyama T, Choi S-H, Tohda C. New reliable scoring system, Toyama Mouse Score, to evaluate locomotor function following spinal cord injury in mice. BMC Research Notes, 7(1):332, 2014.

    21. Kuboyama T, Luo X, Park K, Blackmore MG, Tojima T, Tohda C, Bixby JL, Lemmon VP, Kamiguchi H. Paxillin phosphorylation counteracts proteoglycan-mediated inhibition of axon regeneration. Experimental Neurology, 248, 157-169, 2013.

    22. Teshigawara K, Kuboyama T, Shigyo M, Nagata A, Sugimoto K, Matsuya Y, Tohda C. A novel compound, Denosomin ameliorates spinal cord injury via axonal growth associated with astrocyte-secreted vimentin. British Journal of Pharmacology, 168(4), 903-919, 2013.

    23. Tohda C, Urano T, Umezaki M, Nemere I, Kuboyama T. Diosgenin is an exogenous activator of 1,25D(3)-MARRS/Pdia3/ERp57 and improves Alzheimer’s disease pathologies in 5XFAD mice. Scientific Reports 2:535, 2012.

    24. Tohda C, Nakada R, Urano T, Okonogi A, Kuboyama T. Kamikihi-to (KKT) rescues axonal and synaptic degeneration associated with memory impairment in a mouse model of Alzheimer’s disease, 5XFAD. International Journal of Neuroscience, 121(12), 641-648, 2011.

    25. Kuboyama T, Tohda C, Komatsu K. Withanoside IV and its metabolite, sominone, attenuate Aβ(25-35)-induced neurodegeneration. European Journal of Neuroscience, 23(6), 1417-1426, 2006.

    26. Tohda C, Hashimoto I, Kuboyama T, Komatsu K. Metabolite 1 of protopanaxadiol-type saponins, an axonal regenerative factor, stimulates teneurin-2 linked by PI3-kinase cascade. Neuropsychopharmacology, 31(6), 1158-64, 2006.

    27. Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. British Journal of Pharmacology, 144(7), 961-971, 2005.

    28. Kuboyama T, Tohda C, Zhao J, Nakamura N, Hattori M, Komatsu K. Axon- or dendrite-predominant outgrowth induced by constituents from Ashwagandha. NeuroReport, 13(14), 1715-1720, 2002.

    29. Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K. Withanolide derivatives from roots of Withania somnifera and their neurite outgrowth activities. Chemical and Pharmaceutical Bulletin, 50(6), 760-765, 2002.

    30. Tohda C, Kuboyama T, Komatsu K. Dendrite extension by methanol extract of Ashwagandha (roots of Withania somnifera) in SK-N-SH cells. NeuroReport, 11(9), 1981-1985, 2000.

  • (総説等)
    1. Kuboyama T, Yang X, Tohda C. Natural Medicines and Their Underlying Mechanisms of Prevention and Recovery from Amyloid Β-Induced Axonal Degeneration in Alzheimer’s Disease. International Journal of Molecular Sciences, 21(13):4665, 2020.

    2. 久保山友晴.軸索伸長を基盤とした神経変性疾患治療法の開発.Yakugaku-Zasshi, 139(11): 1385-1390, 2019.

    3. Tohda C, Kuboyama T. Current and future therapeutic strategies for functional repair of spinal cord injury. Pharmacology & Therapeutics, 132(1):57-71, 2011.

    4. Tohda C, Komatsu K, Kuboyama T. Scientific basis for the anti-dementia drugs of constituents from Ashwagandha (Withania somnifera). Journal of Traditional Medicine, 22(Suppl.1), 176-182, 2005.

    5. Tohda C, Kuboyama T, Komatsu K. Search for natural products related to regeneration of the neuronal network. NeuroSignals, 14(1-2), 34-45, 2005.

  • (学会発表)
    1. 久保山友晴、荒毛優太、南雲美咲、小湊誠也、東田千尋. 遠志成分sibiricose A5による抗アルツハイマー病作用. 第38回和漢医薬学会学術大会(web)2021,9,4-5

    2. 久保山友晴、小湊誠也、南雲美咲、東田千尋. 遠志によるマイクログリアM2化を介した脊髄損傷からの回復. 第94回日本薬理学会年会(札幌) 2021,3,8-10

    3. 久保山友晴 アルツハイマー病の予防と治療を目指した和漢薬研究 令和2年度第3回日本東洋医学会福岡県部会(Web)2021,1,24(招待講演)

    4. 久保山友晴、楊熙蒙、東田千尋 アミロイドβによる軸索変性に着目したアルツハイマー病予防・治療法の開発 第37回和漢医薬学会学術大会(Web)2020,8,29-30(招待講演)

    5. 久保山友晴 神経変性疾患の根本治療を目指した和漢薬研究 第36回和漢医薬学会学術大会(富山市)2019, 8, 31- 9, 1. (学術貢献賞受賞講演)

    6. Kuboyama T, Tohda C. HDAC3 inhibition ameliorates memory function via M2 microglia in a transgenic mouse model of Alzheimer’s disease. Neuroscience 2019 (Chicago, U.S.A.) 2019,10,19-23

    7. 久保山友晴 軸索伸長を基盤とした神経変性疾患治療法の開発 日本薬学会北陸支部第130回例会(富山市)2018,11,18(学術奨励賞受賞講演)

    8. 久保山友晴 アルツハイマー病の予防と治療を目指した和漢薬研究 第35回和漢医薬学会学術大会(岐阜市)2018, 9, 1-2. (招待講演)

    9. 久保山友晴、楊志友、東田千尋 アルツハイマー病治療を目指した伝統薬物研究 日本薬学会北陸支部第128回例会(金沢市)2016,11,27 (招待講演)

    10. Kuboyama T, Huang Y, Wong JK, Koemeter-Cox A, Martini M, Friedel RH, Zou H. HDAC3 inhibition ameliorates spinal cord injury by modulation of innate immune response. Neuroscience 2016 (San Diego, U.S.A.) 2016, 11, 12-16.

  • (特許出願・取得)
    1. Kuboyama T, Zou H: Patent Application Number 62/332,967 2016, 4,15 (U.S.A.)

  • (競争的資金獲得状況)
    1. 日本学術振興会 科学研究費助成事業 基盤研究(C)「神経疾患に有効な高付加価値「大黄」の開発研究」2021年 – 2023年(研究分担)

    2. 上原記念生命科学財団 研究助成金「神経回路網再構築を介した根本的不安障害治療法の確立」2020年- 2022年(研究代表)

    3. 武田科学振興財団 薬学系研究奨励「M2マイクログリアによる軸索伸長作用を介した新規脊髄損傷治療法の開発」2019年 – 2022年(研究代表)

    4. 日本学術振興会 科学研究費助成事業 基盤研究(C)「マイクログリアのM2化によるアルツハイマー病根本的治療法の開発」2018年 – 2021年(研究代表)

    5. ロータリー財団 グローバル補助金「軸索再生を司る遺伝子発現制御機構の解明」2015年 – 2016年(研究代表)

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