Development of therapy targeting dysregulation of cell cycle and JNK pathway in polyglutamine diseases
Project/Area Number |
23390230
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Nagoya University |
Principal Investigator |
KATSUNO MASAHISA 名古屋大学, 医学(系)研究科(研究院), 准教授 (50402566)
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Co-Investigator(Kenkyū-buntansha) |
SOBUE Gen 名古屋大学, 医学系研究科, 教授 (20148315)
TANAKA Fumiaki 横浜市立大学, 医学研究科, 教授 (30378012)
ADACHI Hiroaki 名古屋大学, 医学系研究科, 寄附講座准教授 (40432257)
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Project Period (FY) |
2011-04-01 – 2014-03-31
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2011: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
|
Keywords | ポリグルタミン病 / 球脊髄性筋萎縮症 / 神経変性 / 細胞周期 / JNK / 運動ニューロン / サイクリン依存性キナーゼ / ポリグルタミン / マイクロアレイ / 神経変性疾患 / CGRP1 / naratriptan / 転写障害 / 神経ペプチド / セロトニン受容体 |
Research Abstract |
Polyglutamine diseases are a group of hereditary neurodegenerative disorders caused by an expansion of genomic CAG trinucleotide expansion. Intra-neuronal accumulation of causative protein is construed as a pivotal molecular event in the pathogenesis of polyglutamine diseases. Our study demonstrated that dysregulation of cell cycle and abnormal activation of JNK pathway underlie the motor neuron degeneration in spinal and bulbar muscular atrophy (SBMA). We also showed that pharmacological suppression of JNK ameliorates polyglutamine-mediated neurodegeneration in SBMA.
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Report
(4 results)
Research Products
(53 results)
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[Journal Article] Anti-androgen flutamide protects male mice from androgen-dependent toxicity in three models of spinal bulbar muscular atrophy2014
Author(s)
Renier KJ, Troxell-Smith SM, Johansen JA, Katsuno M, Adachi H, Sobue G, Chua JP, Sun Kim H, Lieberman AP, Breedlove SM, Jordan CL
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Journal Title
Endocrinology
Volume: (in press)
Related Report
Peer Reviewed
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[Journal Article] Paeoniflorin eliminates a mutant AR via NF-YA-dependent proteolysis in spinal and bulbar muscular atrophy2014
Author(s)
Tohnai G, Adachi H, Katsuno M, Doi H, Matsumoto S, Kondo N, Miyazaki Y, Iida M, Nakatsuji H, Qiang Q, Ding Y, Watanabe H, Yamamoto M, Ohtsuka K, Sobue G
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Journal Title
Hum Mol Genet
Volume: (in press)
Related Report
Peer Reviewed
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[Journal Article] Tongue pressure as a novel biomarker of spinal and bulbar muscular atrophy (SBMA)2014
Author(s)
Mano T, Katsuno M, Banno H, Suzuki K, Suga N, Hashizume A, Araki A, Watanabe H, Tanaka S, Yamamoto M, Sobue G
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Journal Title
Neurology
Volume: 82
Issue: 3
Pages: 255-262
DOI
Related Report
Peer Reviewed
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[Journal Article] p62/SQSTM1 differentially removes the toxic mutant androgen receptor via autophagy and inclusion formation in a spinal and bulbar muscular atrophy mouse model2013
Author(s)
Doi H, Adachi H, Katsuno M, Minamiyama M, Matsumoto S, Kondo N, Miyazaki Y, IidaM,Tohnai G, Qiang Q, Tanaka F, Yanagawa T, WarabiE,Ishii T, Sobue G
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Journal Title
J Neurosci
Volume: 33
Issue: 18
Pages: 7710-7727
DOI
Related Report
Peer Reviewed
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[Journal Article] Genistein, a natural product derived from soybeans, ameliorates polyglutamine-mediated motor neuron disease2013
Author(s)
Qiang Q, Adachi H, Huang Z, Jiang YM, Katsuno M, Minamiyama M, Doi H, Matsumoto S, Kondo N, Miyazaki Y, Iida M, Tohnai G, Sobue G
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Journal Title
J Neurochem
Volume: 126
Issue: 1
Pages: 122-130
DOI
Related Report
Peer Reviewed
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[Journal Article] Heat shock factor-1 influences pathological lesion distribution of polyglutamine-induced neurodegeneration2013
Author(s)
Kondo N, Katsuno M, Adachi H, Minamiyama M, Doi H, Matsumoto S, Miyazaki Y, Iida M, Tohnai G, Nakatsuji H, Ishigaki S, Fujioka Y, Watanabe H, Tanaka F, Nakai A, Sobue G
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Journal Title
Nat Commun
Volume: 4
Issue: 1
Pages: 1405-1405
DOI
Related Report
Peer Reviewed
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[Journal Article] A functional deficiency of TERA/VCP/p97 contributes to impaired DNA repair in multiple polyglutamine diseases.2013
Author(s)
Fujita K, Nakamura Y, Oka T, Ito H, Tamura T, Tagawa K, Sasabe T, Katsuta A, Motoki K, Shiwaku H, Sone M, Yoshida C, Katsuno M, Eishi Y, Murata M, Taylor JP, Wanker EE, Kono K, Tashiro S, Sobue G, La Spada AR, Okazawa H.
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Journal Title
Nat Commun.
Volume: 4
Issue: 1
Pages: 1816-1816
DOI
Related Report
Peer Reviewed
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[Journal Article] Naratriptan mitigates CGRP1-associated motor neuron degeneration caused by expanded polyglutamine2012
Author(s)
Minamiyama M, Katsuno M, Adachi H, Doi H, Kondo N, Iida M, Ishigaki S, Fujioka Y, Matsumoto S, Miyazaki Y, Tanaka F, Kurihara H, Sobue G
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Journal Title
Nat Med
Volume: 18
Issue: 10
Pages: 1531-1538
DOI
Related Report
Peer Reviewed
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[Journal Article] Cross-sectional and longitudinal analysis of an oxidative stress biomarker for spinal and bulbar muscular atrophy.2012
Author(s)
Mano, T., Katsuno, M., Banno, H., Suzuki, K., Suga, N., Hashizume, A., Tanaka, F., Sobue, G.
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Journal Title
Muscle Nerve
Volume: 46
Issue: 5
Pages: 692-697
DOI
Related Report
Peer Reviewed
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[Journal Article] Longitudinal changes of outcome measures in spinal and bulbar muscular atrophy.2012
Author(s)
Hashizume, A., Katsuno, M., Banno, H., Suzuki, K., Suga, N., Mano, T., Atsuta, N., Oe, H., Watanabe, H., Tanaka, F., Sobue, G.
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Journal Title
Brain
Volume: 35
Issue: 9
Pages: 2838-2848
DOI
Related Report
Peer Reviewed
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[Presentation] Genistein, a natural product derived from soybeans, ameliorates polyglutamine-mediated motor neuron disease2013
Author(s)
Adachi H, Qiang Q, Hunag Z, Jinag YM, Katsuno M, Kondo N, Miyazaki Y, Iida M, Tohnai G, Nakatsuji H, Sobue G
Organizer
Neuroscience 2013
Place of Presentation
San Diego, USA
Related Report
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[Presentation] Deficits in brain-derived neurotrophic factor may underlie motor dysfunction in spinal bulbar muscular atrophy.2013
Author(s)
Hlievski, K., Henley, C.L., Fu, M., Katsuno, M., Adachi, H., Sobue, G., Breedlove, S.M., Jordan, C.L.
Organizer
Neuroscience 2013
Place of Presentation
San Diego,USA
Related Report
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[Presentation] Genistein, a natural product derived from soybeans, ameliorates polyglutamine-mediated motor neuron disease.2013
Author(s)
Adachi, H., Qiang, Q., Hunag, Z., Jinag, Y.M., Katsuno, M., Kondo, N., Miyazaki, Y., Iida, M., Tohnai, G., Nakatsuji, H., Sobue, G.
Organizer
Neuroscience 2013
Place of Presentation
San Diego, USA
Related Report
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[Presentation] Heat shock factor-1 (Hsf-1) controls pathological lesion distribution of polyglutamine-induced motor neuron disease.2013
Author(s)
Kondo, N., Katsuno, M., Adachi, H., Minamiyama, M., Matsumoto, S., Nakatsuji, H., Miyazaki, Y., Iida, M., Tohnai, G., Sobue, G.
Organizer
The 24th International Symposium on ALS/MND
Place of Presentation
Milan, Italy
Related Report
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[Presentation] Cell cycle dysregulation in motor neurons of spinal and bulbar muscular atrophy (SBMA)2012
Author(s)
Katsuno M, Adachi H, Kondo N, Minamiyama M, Doi H, Matsumoto S, Miyazaki Y, Iida M, Nakatsuji H, Tanaka F, Sobue G
Organizer
23rd International Symposium on ALS/MND
Place of Presentation
Chicago, USA
Related Report
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[Presentation] p62/SQSTM1 removes toxic mutant androgen receptor in spinal bulbar muscular atrophy model mouse2012
Author(s)
Adachi H, Doi H, Katsuno M, Matsumoto S, Kondo N, Miyazaki Y, Tohnai G, Iida M, Tanaka F, Sobue G
Organizer
Neuroscience 2012
Place of Presentation
New Orleans, USA
Related Report
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[Presentation] Naratriptan ameliorates SBMA pathology by the repression of CGRP1-activated JNK pathway2012
Author(s)
Minamiyama M, Katsuno M, Adachi H, Doi H, Kondo N, Iida M, Ishigaki S, Fujioka Y, Matsumoto S, Miyazaki Y, Tanaka F, Kurihara H, Sobue G
Organizer
Neuroscience 2012
Place of Presentation
New Orleans, USA
Related Report
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[Presentation] Cell cycle dysregulation in motor neurons of spinal and bulbar muscular atrophy (SBMA).2012
Author(s)
Katsuno M, Adachi H, Kondo N, Minamiyama M, Doi H, Matsumoto S, Miyazaki Y, Iida M, Nakatsuji H, Tanaka F, Sobue G.
Organizer
23rd International Symposium on ALS/MND.
Place of Presentation
Chicago, USA
Related Report
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[Presentation] Longitudinal changes of outcome measures in spinal and bulbar muscular atrophy.2012
Author(s)
Hashizume A, Katsuno M, Banno H, Suzuki K, Suga N, Mano T, Atsuta N, Oe H, Watanabe H, Tanaka F, Sobue G.
Organizer
23rd International Symposium on ALS/MND.
Place of Presentation
Chicago, USA
Related Report
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[Presentation] Naratriptan ameliorates SBMA pathology by the repression of CGRP1-activated JNK pathway.2012
Author(s)
Minamiyama M, Katsuno M, Adachi H, Doi H, Kondo N, Iida M, Ishigaki S, Fujioka Y, Matsumoto S, Miyazaki Y, Tanaka F, Kurihara H, Sobue G.
Organizer
Neuroscience 2012
Place of Presentation
New Orleans, USA
Related Report
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[Presentation] CGRP1 is the new therapeutic target for SBMA (Spinal and Bulbar Muscular Atrophy).2012
Author(s)
Minamiyama M, Katsuno M, Adachi H, Doi H, Kondo N, Iida M, Ishigaki S, Fujioka Y, Matsumoto S, Miyazaki Y, Tanaka F, Kurihara H, Sobue G.
Organizer
11th Biennial Meeting of the Asian Pacific Society for Neurochemistry.
Place of Presentation
神戸国際会議場(神戸)
Related Report
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[Presentation] A peony extract enhances protein degradation systems and exerts therapeutic effects in the polyglutamine-mediated motor neuron disease2011
Author(s)
Adachi H, Tohnai G, Katsuno M, Minamiyama M, Doi H, Matsumoto S, Kondo N, Miyazaki Y, Tanaka F, Ohtsuka K, Sobue G
Organizer
Neuroscience 2011
Place of Presentation
Washington DC, USA
Related Report
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[Presentation] Effect of leuprorelin in patients with spinal and bulbar muscular atrophy (SBMA) : a multicenter, randomized, double-blind, placebo-controlled trial2011
Author(s)
Banno H, Katsuno M, Suzuki K, Takeuchi Y, Kawashima M, Yabe I, Sasaki H, Aoki M, Morita M, Nakano I, Kanai K, Ito S, Ishikawa K, Mizusawa H, Yamamoto T, Tsuji S, Hasegawa K, Shimohata T, Nishizawa M, Miyajima H, Kanda F, Watanabe Y, Nakashima K, Tsujino A, Yamashita T, Uchino M, Fujimoto Y, Tanaka F, Sobue G; for the Japan SBMA Interventional Trial for TAP-144-SR (JASMITT) study group
Organizer
63rd American Academy of Neurology Annual Meeting
Place of Presentation
Honolulu, USA
Related Report
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[Presentation] Central motor conduction time (CMCT) in patients with spinal and bulbar muscular atrophy (SBMA)2011
Author(s)
Suzuki K, Katsuno M, Banno H, Suga N, Hashizume A, Hara T, Hama T, Nakamura T, Hirayama M, Tanaka F, Sobue G
Organizer
15th Congress of the European Federation of Neurological Societies
Place of Presentation
Budapest, Hungary
Related Report
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