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Translational study of molecular pathogenesis on dystonia and developing its novel therapeutic interventions

Research Project

Project/Area Number 21390269
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionThe University of Tokushima

Principal Investigator

KAJI Ryuji  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (00214304)

Co-Investigator(Kenkyū-buntansha) GOTO Satoshi  徳島大学, 病院, 講師 (50240916)
ASANUMA Koutaro  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 講師 (80448323)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords臨床神経生理学 / 神経科学 / 脳神経疾患 / 遺伝子 / ゲノム / 国際協力 / ジストニア / DYT3 / PET
Research Abstract

Dystonia is about one fourth as frequent as parkinsonism, and is not a rare disorder. It incapacitates sufferers to be bed-ridden if advanced. We for the first time found the gene(TAF-1) causing a hereditary dystonia DYT3, which is now being reported in Japan. It is therefore important to search for its pathogenesis and therapy. We previously found selective loss of neurons in striosome in the striatum of the basal ganglia in DYT3 autopsied brains. In this research, we found that NTAF-1, a neuron-specific isoform of TAF-1 is mainly localized in the striosome, which links the molecular pathogenesis with pathological and clinical findings.
We also reported clinical usefulness of zolpidem for treating dystonia in general. We developed a screening test for DYT3 dystonia, and tried a surgical treatment on a DYT3 patient with excellent outcomes.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (44 results)

All 2012 2011 2010 2009

All Journal Article (28 results) (of which Peer Reviewed: 28 results) Presentation (13 results) Book (3 results)

  • [Journal Article] Efficacy of zolpidem for dystonia : a study among different subtypes2012

    • Author(s)
      Miyazaki Y, Sako W, Asanuma K, Izumi Y, Miki T, Kaji R.
    • Journal Title

      Frontiers in neurology

      Volume: 3 Pages: 58-58

    • NAID

      120006869520

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reduced serum ceruloplasmin levels in cervical dystonia2012

    • Author(s)
      Mezaki T, Kaji R.
    • Journal Title

      European neurology

      Volume: 67 Pages: 256-256

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cell type-specific localization of optineurin in the striatal neurons of mice : implications for neuronal vulnerability in Huntington' s disease2012

    • Author(s)
      Okita S, Morigaki R, Koizumi H, Kaji R, Nagahiro S, Goto S.
    • Journal Title

      Neuroscience

      Volume: 202 Pages: 363-370

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential2012

    • Author(s)
      Kuroda Y, Sako W, Goto S, Kaji R et al.
    • Journal Title

      Human molecular genetics

      Volume: 21 Pages: 991-1003

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Type A1 but not type A2 botulinum toxin decreases the grip strength of the contralateral foreleg through axonal transport from the toxin-treated foreleg of rats2011

    • Author(s)
      Torii Y, Akaike N, Harakawa T, Kaji R et al.
    • Journal Title

      Journal of pharmacological sciences

      Volume: 117 Pages: 275-285

    • NAID

      10030453790

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] New and emerging indications of botulinum toxin therapy2011

    • Author(s)
      Kaji R.
    • Journal Title

      Parkinsonism & related disorders

      Volume: 17

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Practical management of botulinum toxin therapy2011

    • Author(s)
      Lim EC, Bhidayasiri R, Rosales RL, Kaji R.
    • Journal Title

      Introduction. Parkinsonism & related disorders

      Volume: 17 Issue: 2 Pages: 123-5

    • DOI

      10.1016/j.parkreldis.2010.11.013

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification and localization of a neuron-specific isoform of TAF1 in rat brain : implications for neuropathology of DYT3 dystonia2011

    • Author(s)
      Sako W, Morigaki R, Kaji R, et al.
    • Journal Title

      Neuroscience

      Volume: 189 Pages: 100-107

    • DOI

      10.1016/j.neuroscience.2011.05.031

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bilateral pallidal deep brain stimulation in primary Meige syndrome2011

    • Author(s)
      Sako W, Morigaki R, Mizobuchi Y, Kaji R et al.
    • Journal Title

      Parkinsonism & related disorders

      Volume: 17 Pages: 123-125

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy2011

    • Author(s)
      Taniguchi-Ikeda M, Kobayashi K, Kanagawa M, Yu CC, Mori K, Oda T, Kuga A, Kurahashi H, Akman HO, DiMauro S, Kaji R, Yokota T, Takeda S, Toda T
    • Journal Title

      Nature

      Volume: 478 Issue: 7367 Pages: 127-131

    • DOI

      10.1038/nature10456

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The UCHL1 S18Y polymorphism and Parkinson's disease in a Japanese population.2011

    • Author(s)
      Snapinn KW, Larson EB, Kawakami H, Ujike H, Borenstein AR, Izumi Y, Kaji R, Maruyama H, Mata IF, Morino H, Oda M, Tsuang DW, Yearout D, Edwards KL, Zabetian CP.
    • Journal Title

      Parkinsonism Relat Disord

      Volume: 21(Epub ahead of print)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Temporal evolution of sporadic Creutzfeldt-Jakob disease monitored by 3-Tesla MR spectroscopy.2011

    • Author(s)
      Fujita K, Harada M, Yuasa T, Sasaki M, Izumi Y, Kaji R.
    • Journal Title

      J Neurol

      Volume: 17(Epub ahead of print)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations of optineurin in amyotrophic lateral sclerosis2010

    • Author(s)
      Maruyama H, Morino H, Ito H, . Kaji R, Kawakami H.
    • Journal Title

      Nature

      Volume: 465 Pages: 223-226

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Olfactory type G-protein alpha subunit in striosome-matrix dopamine systems in adult mice2010

    • Author(s)
      Sako W, Morigaki R, Nagahiro S, Kaji R, Goto S.
    • Journal Title

      Neuroscience

      Volume: 170 Pages: 497-502

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bilateral pallidal deep brain stimulation in primary Meige syndrome.2010

    • Author(s)
      Sako W, Morigaki R, Mizobuchi Y, Tsuzuki T, Ima H, Ushio Y, Nagahiro S, Kaji R, Goto S.
    • Journal Title

      Parkinsonism Relat Disord

      Volume: 17 Pages: 123-5

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of effects of botulinum toxin subtype A1 and A2 using twitch tension assay and rat grip strength test.2010

    • Author(s)
      Torii Y, Kiyota N, Sugimoto N, Mori Y, Goto Y, Harakawa T, Nakahira S, Kaji R, Kozaki S, Ginnaga A.
    • Journal Title

      Toxicon

      Volume: 57 Pages: 93-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of A2 type botulinum toxin on spontaneous miniature and evoked transmitter release from the rat spinal excitatory and inhibitory synapses.2010

    • Author(s)
      Akaike N, Ito Y, Shin MC, Nonaka K, Torii Y, Harakawa T, Ginnaga A, Kozaki S, Kaji R.
    • Journal Title

      Toxicon

      Volume: 56 Pages: 1315-26

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Olfactory type G-protein alpha subunit in striosome-matrix dopamine systems in adult mice.2010

    • Author(s)
      Sako W, Morigaki R, Nagahiro S, Kaji R, Goto S.
    • Journal Title

      Neuroscience

      Volume: 13 Pages: 497-502

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Entrapment neuropathy and beyond.2010

    • Author(s)
      Kaji R.
    • Journal Title

      J Physiol

      Volume: 1

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term suppression of Meige syndrome after pallidal stimulation : a 10-year follow-up study2010

    • Author(s)
      Inoue N, Nagahiro S, Kaji R, Goto S.
    • Journal Title

      Mov Disord

      Volume: 15 Pages: 1756-8

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GSK1358820 Spasticity Study Group. Botulinum toxin type A in post-stroke upper limb spasticity.2010

    • Author(s)
      Kaji R, Osako Y, Suyama K, Maeda T, Uechi Y, Iwasaki M
    • Journal Title

      Curr Med Res Opin

      Volume: 26 Pages: 1983-92

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations of optineurin in amyotrophic lateral sclerosis.2010

    • Author(s)
      Maruyama H, Morino H, Ito H, Izumi Y, Kato H, Watanabe Y, Kinoshita Y, Kamada M, Nodera H, Suzuki H, Komure O, Matsuura S, Kobatake K, Morimoto N, Abe K, Suzuki N, Aoki M, Kawata A, Hirai T, Kato T, Ogasawara K, Hirano A, Takumi T, Kusaka H, Hagiwara K, Kaji R, Kawakami H.
    • Journal Title

      Nature

      Volume: 13 Pages: 223-6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Botulinum toxin type A in post-stroke lower limb spasticity : a multicenter, double-blind, placebo-controlled trial.2010

    • Author(s)
      Kaji R, Osako Y, Suyama K, Maeda T, Uechi Y, Iwasaki M
    • Journal Title

      J Neurol

      Volume: 257 Pages: 1330-7

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease.2009

    • Author(s)
      Zabetian CP, Yamamoto M, Lopez AN, Ujike H, Mata IF, Izumi Y, Kaji R, Maruyama H, Morino H, Oda M, Hutter CM, Edwards KL, Schellenberg GD, Tsuang DW, Yearout D, Larson EB, Kawakami H.
    • Journal Title

      Mov Disord 24

      Pages: 1034-1041

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Subthalamic nucleus deep brain stimulation for camptocormia associated with Parkinson's disease.2009

    • Author(s)
      Sako W, Nishio M, Maruo T, Shimazu H, Matsuzaki K, Tamura T, Mure H, Ushio Y, Nagahiro S, Kaji R, Goto S.
    • Journal Title

      Mov Disord 24

      Pages: 1076-1079

    • NAID

      10024369634

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] uantitative determination of the biological activity of botulinum toxin type A by measuring the compound muscle action potential (CMAP) in rats.2009

    • Author(s)
      Sakamoto T, Torii Y, Takahashi M, Ishida S, Goto Y, Nakano H, Harakawa T, Ginnaga A, Kozaki S, Kaji R.
    • Journal Title

      Toxicon 54

      Pages: 857-861

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term suppression of tremor by deep brain stimulation of the ventral intermediate nucleus of the thalamus combined with pallidotomy in hemiparkinsonian patients.2009

    • Author(s)
      Nishio M, Korematsu K, Yoshioka S, Nagai Y, Maruo, T, Ushio Y, Kaji R, Goto S.
    • Journal Title

      J Clin Neurosci 16

      Pages: 1489-1491

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Screening for TARDBP mutations in Japanese familial amyotrophic lateral sclerosis2009

    • Author(s)
      Kamada M, Maruyama H, Tanaka E, Morino H, Wate R, Ito H, Kusaka H, Kawano Y, Miki T, Nodera H, Izumi Y, Kaji R, Kawakami H.
    • Journal Title

      J Neurol Sci 284

      Pages: 69-71

    • NAID

      120001898369

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Neuropathology update Lessons from DYT3 and other dystonias2011

    • Author(s)
      Kaji R
    • Organizer
      5th INTERNATIONAL DYSTONIA SYMPOSIUM BARCELONA
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2011-10-20
    • Related Report
      2011 Final Research Report
  • [Presentation] Neuropathology update : Lessons from DYT3 and other dystonias2011

    • Author(s)
      Kaji R
    • Organizer
      5th INTERNATIONAL DYSTONIA SYMPOSIUM BARCELONA
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2011-10-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] Japanese study experience sharing Upper limb study(BTX108509)2010

    • Author(s)
      Kaji R
    • Organizer
      Lower limb study(BTX108512) Injection Training for the Study to Evaluate the Efficacy and Safety in Chinese Patients with Post-Stroke Upper Limb Spasticity
    • Place of Presentation
      Building, China
    • Year and Date
      2010-03-13
    • Related Report
      2011 Final Research Report
  • [Presentation] Japanese study experience sharing Upper limb study(BTX108509)/Lower limb study(BTX108512)2010

    • Author(s)
      梶龍兒
    • Organizer
      Injection Training for the Study to Evaluate the Efficacy and Safety in Chinese Patients with Post-Stroke Upper Limb Spasticity
    • Place of Presentation
      中国 上海The Headquarters Building No168 Tibet Road(M)
    • Year and Date
      2010-03-13
    • Related Report
      2009 Annual Research Report
  • [Presentation] Multifocal Motor neuropathy : Prof Bostock's contribution to clarify its pathophysiology2009

    • Author(s)
      梶龍兒
    • Organizer
      Festschrift in honour of Prof. Hugh Bostok, FRS
    • Place of Presentation
      イギリス ロンドンBasement Lecture Theatre
    • Year and Date
      2009-11-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] Molecular dissection of dystonia2009

    • Author(s)
      Kaji R
    • Organizer
      19^<th> World Congress of Neurology
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2009-10-29
    • Related Report
      2011 Final Research Report
  • [Presentation] Molecular dissection of dystonia2009

    • Author(s)
      梶龍兒
    • Organizer
      19th World Congress of Neurology
    • Place of Presentation
      タイ バンコクThe Bang kok International Trade & Exhibition Centre
    • Year and Date
      2009-10-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] Dopa-responsive dystonias : An update MDS2009

    • Author(s)
      Kaji R
    • Organizer
      13th International Congress
    • Place of Presentation
      Paris, France
    • Year and Date
      2009-06-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Dopa-responsive dystonias : An update2009

    • Author(s)
      梶龍兒
    • Organizer
      MDS 13th International Congress
    • Place of Presentation
      フランス パリLe Palais Des Congres de Paris
    • Year and Date
      2009-06-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Multifocal Motor Neuropathy2009

    • Author(s)
      梶龍兒
    • Organizer
      Neuromuscular Symposium in Honor of Austin J.Sumner, M.D
    • Place of Presentation
      アメリカ ニューオーリンズLousiana State University Health Sciencea Center Mediacl Eduaction Building
    • Year and Date
      2009-05-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] Therapeutic approach to spasticity : an update2009

    • Author(s)
      梶龍兒
    • Organizer
      2009 Asian and Oceanian Congress on Clinical Neurophysiology
    • Place of Presentation
      韓国 ソウルSheraton Grand Walkerhill Hotel
    • Year and Date
      2009-04-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] Pathophysiology of dystonia 2009 Spring KMDS Sympo2009

    • Author(s)
      Kaji R
    • Place of Presentation
      Soul South Korea
    • Year and Date
      2009-04-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Pathophysiology of dystonia2009

    • Author(s)
      梶龍兒
    • Organizer
      2009 Spring KMDS Sympo
    • Place of Presentation
      韓国 ソウルGrand Hyatt Hotel
    • Year and Date
      2009-04-11
    • Related Report
      2009 Annual Research Report
  • [Book] ボツリヌス療法アトラス2012

    • Author(s)
      梶龍兒
    • Publisher
      医学書院
    • Related Report
      2011 Final Research Report
  • [Book] ジストニア診療とケアマニュアル2012

    • Author(s)
      堀内正浩・梶龍兒
    • Total Pages
      48
    • Publisher
      診断と治療社
    • Related Report
      2011 Annual Research Report
  • [Book] ジストニア診療とケアマニュアル2011

    • Author(s)
      堀内正浩、梶龍兒
    • Publisher
      診断と治療社
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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