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2010 Fiscal Year Final Research Report

Therapeutic strategy for polyglutamine-mediated motor neuron disease via molecular chaperone-ubiquitin proteasome system

Research Project

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Project/Area Number 20390243
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionNagoya University

Principal Investigator

ADACHI Hiroaki  Nagoya University, 医学系研究科, COE特任講師 (40432257)

Co-Investigator(Kenkyū-buntansha) SOBUE Gen  名古屋大学, 大学院・医学系研究科, 教授 (20148315)
TANAKA Fumiaki  名古屋大学, 大学院・医学系研究科, 准教授 (30378012)
KATSUNO Masahisa  名古屋大学, 高等研究院, 特任講師 (50402566)
Project Period (FY) 2008 – 2010
Keywords球脊髄性筋萎縮症 / ポリグルタミン病 / 分子シャペロン / ペオニ抽出物
Research Abstract

We administrated the peony extract to male spinal and bulbar muscular atrophy (SBMA) transgenic mouse model (androgen receptor (AR)-97Q or AR-24Q) and examined various neurological and behavioral parameters. Administration of the peony extract markedly ameliorated motor impairments in AR-97Q mice without detectable toxicity, and reduced amounts of monomeric and nuclear accumulated mutant AR. Mutant AR was preferentially degraded in the presence of the compound in both SBMA cell and mouse models when compared with wild-type AR. It also significantly induced Hsp70 and Hsp40. These observations suggest that the compound is a promising therapeutic candidate for polyglutamine (polyQ)-mediated neurodegenerative diseases including SBMA.

  • Research Products

    (21 results)

All 2011 2010 2009 2008

All Journal Article (17 results) Presentation (4 results)

  • [Journal Article] Suppression of Alzheimer's disease-related phenotypes by expression of heat shock protein 70 in mice.2011

    • Author(s)
      Hoshino T, Murao N, Namba T, Takehara M, Adachi H, Katsuno M, Sobue G, Matsushima T, Suzuki T, Mizushima T.
    • Journal Title

      J Neurosci31

      Pages: 5225-5234

  • [Journal Article] Transforming Growth Factor-β Signaling in Motor Neuron Diseases.2011

    • Author(s)
      Katsuno M, Adachi H, Banno H, Suzuki K, Tanaka F, Sobue G.
    • Journal Title

      Curr Mol Med 11

      Pages: 48-56

  • [Journal Article] Microarray Analysis of Gene Expression by Skeletal Muscle of Three Mouse Models of Kennedy Disease/Spinal Bulbar Muscular Atrophy.2010

    • Author(s)
      Mo K, Razak Z, Rao Y, Yu Z, Adachi H, Katsuno M, Sobue G, Lieberman AP, Westwood JT, Monks DA.
    • Journal Title

      PLoS ONE 5

      Pages: 12922

  • [Journal Article] Clinicopathological features of acute autonomic and sensory neuropathy.2010

    • Author(s)
      Koike H, Atsuta N, Adachi H, Iijima M, Katsuno M, Yasuda T, Fukada Y, Yasui K, Nakashima K, Horiuchi M, Shiomi K, Fukui K, Takashima S, Morita Y, Kuniyoshi K, Hasegawa Y, Toribe Y, Kajiura M, Takeshita S, Mukai E, Sobue G.
    • Journal Title

      Brain 133(10)

      Pages: 2881-2896

  • [Journal Article] Clinical features and molecular mechanisms of spinal and bulbar muscular atrophy (SBMA).2010

    • Author(s)
      Katsuno M, Banno H, Suzuki K, Adachi H, Tanaka F, Sobue G.
    • Journal Title

      Adv Exp Med Biol 685

      Pages: 64-74

  • [Journal Article] Disrupted transforming growth factor-beta signaling in spinal and bulbar muscular atrophy.2010

    • Author(s)
      Katsuno M, Adachi H, Minamiyama M, Waza M, Doi H, Kondo N, Mizoguchi H, Nitta A, Yamada K, Banno H, Suzuki K, Tanaka F, Sobue G.
    • Journal Title

      J Neurosci 30

      Pages: 5702-5712

  • [Journal Article] Suppression of melanin production by expression of HSP70.2010

    • Author(s)
      Hoshino T, Matsuda M, Yamashita Y, Takehara M, Fukuya M, Mineda K, Maji D, Ihn H, Adachi H, Sobue G, Funasaka Y, Mizushima T.
    • Journal Title

      J Biol Chem 285

      Pages: 13254-13263

  • [Journal Article] Prevention of ultraviolet B radiation-induced epidermal damage by expression of heat shock protein 70.2010

    • Author(s)
      Matsuda M, Hoshino T, Yamashita Y, Tanaka KI, Maji D, Sato K, Adachi H, Sobue G, Ihn H, Funasaka Y, Mizushima T.
    • Journal Title

      J Biol Chem 285

      Pages: 5848-5858

  • [Journal Article] Dorfin ameliorates phenotypes in a transgenic mouse model of amyotrophic lateral sclerosis.2010

    • Author(s)
      Sone J, Niwa J, Kawai K, Ishigaki S, Yamada S, Adachi H, Katsuno M, Tanaka F, Doyu M, Sobue G.
    • Journal Title

      J Neurosci Res 88

      Pages: 123-135

  • [Journal Article] Heat shock proteins in neurodegenerative diseases : pathogenic roles and therapeutic implications.2009

    • Author(s)
      Adachi H, Katsuno M, Waza M, Minamiyama M, Tanaka F, Sobue G.
    • Journal Title

      Int J Hyperthermia 25

      Pages: 647-654

  • [Journal Article] 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in a SBMA model mouse.2009

    • Author(s)
      Tokui K*, Adachi H*, Waza M, Katsuno M, Minamiyama M, Doi H, Tanaka K, Hamazaki J, Murata S, Tanaka F, Sobue G.
    • Journal Title

      Hum Mol Genet(* Evenly contributed to the study) 18

      Pages: 898-910

  • [Journal Article] Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy.2009

    • Author(s)
      Banno H, Katsuno M, Suzuki K, Takeuchi Y, Kawashima M, Suga N, Takamori M, Ito M, Nakamura T, Matsuo K, Yamada S, Oki Y, Adachi H, Minamiyama M, Waza M, Atsuta N, Watanabe H, Fujimoto Y, Nakashima T, Tanaka F, Doyu M, Sobue G.
    • Journal Title

      Ann Neurol 65

      Pages: 140-150

  • [Journal Article] Getting a handle on Huntington's disease : the case for cholesterol.2009

    • Author(s)
      Katsuno M, Adachi H, Sobue G.
    • Journal Title

      Nat Med 15

      Pages: 253-254

  • [Journal Article] A role for HSP70 in protecting against indomethacin-induced gastric lesions.2009

    • Author(s)
      Suemasu S, Tanaka KI, Namba T, Ishihara T, Katsu T, Fujimoto M, Adachi H, Sobue G, Takeuchi K, Nakai A, Mizushima T.
    • Journal Title

      J Biol Chem 284

      Pages: 19705-19715

  • [Journal Article] HSP70 Confers Protection against Indomethacin-Induced Lesions of the Small Intestine.2009

    • Author(s)
      Teita A, Tanaka KI, Yamakawa N, Adachi H, Sobue G, Goto H, Takeuchi K, Mizushima T.
    • Journal Title

      J Pharmacol Exp Ther 330

      Pages: 458-467

  • [Journal Article] TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases.2009

    • Author(s)
      Iguchi Y, Katsuno M, Niwa JI, Yamada SI, Sone J, Waza M, Adachi H, Tanaka F, Nagata KI, Arimura N, Watanabe T, Kaibuchi K, Sobue G.
    • Journal Title

      J Biol Chem 284

      Pages: 22059-22066

  • [Journal Article] Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy.2009

    • Author(s)
      Palazzolo I, Stack C, Kong L, Musaro A, Adachi H, Katsuno M, Sobue G, Taylor JP, Sumner CJ, Fischbeck KH, Pennuto M.
    • Journal Title

      Neuron 63

      Pages: 316-328

  • [Presentation] A peony extract alleviates polyglutamine-mediated motor neuron disease2010

    • 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
      40th Annual Meeting for the Society for Neuroscience
    • Place of Presentation
      San Diego
    • Year and Date
      2010-11-17
  • [Presentation] Medical induction of stress response alleviates polyglutamine-mediated motor neuron disease The 4th International Congress Responses in Biology and Medicine (CSSI)2009

    • Author(s)
      Tohnai G, Adachi H, Tokui K, Waza M, Katsuno M, Minamiyama M, Doi H, Tanaka F, Ohtsuka K, Sobue G.
    • Organizer
      The 4th Annual Meeting of The Biomedical Society for Stress Response (BSSR)
    • Place of Presentation
      Sapporo(一般演題)
    • Year and Date
      20091006-20091009
  • [Presentation] TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases2009

    • Author(s)
      Iguchi Y, Katsuno M, Niwa JI, Sone J, Waza M, Adachi H, Tanaka F, Nagata KI, Arimura N, Watanabe T, Kaibuchi K, Sobue G.
    • Organizer
      39th Annual Meeting for the Society for Neuroscience
    • Place of Presentation
      Chicago, IL(一般演題)
    • Year and Date
      2009-10-18
  • [Presentation] An oral Hsp9O inhibitor ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model2008

    • Author(s)
      Adachi H, Tokui K, Katsuno M, Minamiyama M, Doi H, Tanaka F, Sobue G.
    • Organizer
      第38回The Society for Neuroscience Annual meeting
    • Place of Presentation
      Washington DC(一般演題)
    • Year and Date
      20081100

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Published: 2012-01-26   Modified: 2016-04-21  

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