• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Research toward the development of a novel treatment for Parkinson disease by a moderate gene silencing with RNA interference.

Research Project

Project/Area Number 24390226
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neurology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

HOHJOH HIROHIKO  独立行政法人国立精神・神経医療研究センター, 神経研究所神経薬理研究部, 室長 (60238722)

Co-Investigator(Kenkyū-buntansha) NAGAI Yoshitaka  独立行政法人国立精神, 神経医療研究センター・疾病研究第4部, 室長 (60335354)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
KeywordsRNAi / パーキンソン病 / α-シヌクレイン / 多重重複変異 / ショウジョウバエ / α‐シヌクレイン
Outline of Final Research Achievements

The alpha-synuclein (SNCA) gene is a responsible gene for Parkinson’s disease (PD); and not only nucleotide variations but also overexpression of SNCA appears to be involved in PD. A specific inhibition against mutant SNCA genes carrying nucleotide variations may be feasible by an allele-specific RNAi; however, there is no method for restoring the SNCA overexpression to a normal level. In this study we showed that an atypical RNAi using siRNAs that confer a moderate level of gene silencing was capable of controlling overexpressed SNCA genes to return to a normal level; named ‘expression-control RNAi’ (ExCont-RNAi). To further assess its therapeutic effects, PD-model flies that carried the human SNCA gene underwent an ExCont-RNAi treatment. The treated PD-flies demonstrated a significant improvement in their motor function. Our current findings suggested that ExCont-RNAi might be capable of becoming a novel therapeutic procedure for PD with the SNCA overexpression.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (31 results)

All 2015 2014 2013 2012 Other

All Journal Article (13 results) (of which Peer Reviewed: 12 results,  Open Access: 2 results,  Acknowledgement Compliant: 3 results) Presentation (13 results) (of which Invited: 1 results) Book (5 results)

  • [Journal Article] Normalization of overexpressed alpha-synuclein causing Parkinson’s disease by a moderate gene silencing with RNA interference.2015

    • Author(s)
      Takahashi M., Suzuki M., Fukuoka M., Fujikake N., Watanabe S., Murata M., Wada K., Nagai Y., and *Hohjoh H.
    • Journal Title

      Mol Ther Nucleic Acids

      Volume: 4 Pages: e241-e241

    • DOI

      10.1038/mtna.2015.14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A novel measurement of allele discrimination for assessment of allele-specific silencing by RNA interference.2014

    • Author(s)
      Takahashi M. and *Hohjoh H.
    • Journal Title

      Mol Biol Rep

      Volume: 41 Issue: 11 Pages: 7115-7120

    • DOI

      10.1007/s11033-014-3586-7

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Gene silencing mediated by endogenous microRNAs under heat stress conditions in mammalian cells.2014

    • Author(s)
      Fukuoka M., Yoshida M., Eda A., Takahashi M., *Hohjoh H.
    • Journal Title

      PLoS ONE

      Volume: 9(7) Issue: 7 Pages: e103130-e103130

    • DOI

      10.1371/journal.pone.0103130

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Disease-associated mutations of TDP-43 promote turnover of the protein through the proteasomal pathway.2014

    • Author(s)
      Araki W., Minegishi S., Motoki K., Kume H., Hohjoh H., Araki YM., and Tamaoka A.
    • Journal Title

      Mol Neurobiol

      Volume: 50 Issue: 3 Pages: 1049-1058

    • DOI

      10.1007/s12035-014-8644-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific inhibition of tumor cells by oncogenic EGFR specific silencing by RNA interference.2013

    • Author(s)
      Takahashi M., Chiyo T., Okada T., and *Hohjoh H.
    • Journal Title

      PLoS ONE

      Volume: 8(8) Issue: 8 Pages: e73214-e73214

    • DOI

      10.1371/journal.pone.0073214

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disease-causing allele-specific silencing by RNA interference.2013

    • Author(s)
      *Hohjoh H.
    • Journal Title

      Pharmaceuticals

      Volume: 6 Issue: 4 Pages: 522-535

    • DOI

      10.3390/ph6040522

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a novel bone morphogenetic protein (BMP)-inducible transcript, BMP-inducible transcript-1, by utilizing the conserved BMP-responsive elements in the Id genes.2013

    • Author(s)
      Shin M, Ohte S, Fukuda T, Sasanuma H, Yoneyama K, Kokabu S, Miyamoto A. Tsukamoto S, Hohjoh H, Jimi E, Katagiri T.
    • Journal Title

      J Bone Miner Metab.

      Volume: 31 Issue: 1 Pages: 34-43

    • DOI

      10.1007/s00774-012-0381-1

    • NAID

      10031168835

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ubiquitin C-terminal hydrolase L1 (UCH-L1) act as a novel potentiator of cyclin-dependent kinases to enhance cell proliferation, independent of its hydrolase activity2013

    • Author(s)
      Kabuta, T., Mitsui, T., Takahashi, M., Fujiwara, Y., Kabuta, C., Konya, C., Tsuchiya, Y., Hatanaka, Y., Uchida, K., Hohjoh, H., Wada, K
    • Journal Title

      J. Biol. Chem

      Volume: 288 Issue: 18 Pages: 12615-12626

    • DOI

      10.1074/jbc.m112.435701

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA expression during neuronal differentiation of human teratocarcinoma NTera2D1 and mouse embryonic carcinoma P19 cells. In MicroRNA Protocols.2013

    • Author(s)
      *Hohjoh H.
    • Journal Title

      Methods Mol Biol

      Volume: 936 Pages: 257-269

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Disease-causing allele specific silencing against the ALK2 mutants, R206H and G356D, in Fibrodysplasia Ossificans Progressiva.2012

    • Author(s)
      Takahashi M., Katagiri T., Furuya H., and Hohjoh H.
    • Journal Title

      Gene Therapy

      Volume: 19 Pages: 781-785

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Active role of small non-coding RNAs derived from SINE/B1 retrotransposon during early mouse development.2012

    • Author(s)
      Ohnishi Y., Totoki Y., Toyoda A., Watanabe T., Yamamoto Y., Tokunaga K., Sakaki Y., Sasaki H., and Hohjoh H.
    • Journal Title

      Mol Biol Rep

      Volume: 39 Pages: 903-909

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenic mutation of ALK2 inhibits iPS cell reprogramming and maintenance : mechanisms of reprogramming and strategy for drug identification.2012

    • Author(s)
      Hamasaki M., Hashizume Y., Yamada Y., Katayama T., Hohjoh H., Fusaki N., Nakashima Y., Turuya H., Haga N., Takami Y., and Era T.
    • Journal Title

      Stem Cells

      Volume: 30 Issue: 11 Pages: 2437-2449

    • DOI

      10.1002/stem.1221

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduction of type IV collagen by upregulated miR-29 in normal elderly mouse and klotho-deficient, senescence-model mouse.2012

    • Author(s)
      Takahashi M., Eda A., Fukushima T., and Hohjoh H.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 11 Pages: e48974-e48974

    • DOI

      10.1371/journal.pone.0048974

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 熱ストレス下におけるマイクロRNAの遺伝子発現制御に関する解析2014

    • Author(s)
      福岡聖之、吉田満史子、枝亜希子、高橋理貴、北條浩彦.
    • Organizer
      第37回日本分子生物学会大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 老化モデルマウスおよび正常加齢マウスにおけるmiR-29の発現上昇とそれに伴うコラーゲンタイプIVの発現低下2014

    • Author(s)
      北條浩彦、高橋理貴、枝亜希子、福島達伸.
    • Organizer
      第59回日本人類遺伝学会大会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Application of atypical RNAi for human diseases.2014

    • Author(s)
      Takahashi M, Nakamura Y, and Hohjoh H.
    • Organizer
      Joint Australia and Japan RNA (jajRNA) meeting
    • Place of Presentation
      the University of Technology, Sydney, Australia
    • Year and Date
      2014-11-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Gene silencing mediated by endogenous miRNAs under heat stress conditions in mammalian cells.2014

    • Author(s)
      Fukuoka M, Yoshida M, Eda A, Takahashi M, and Hohjoh H.
    • Organizer
      64rd Annual Meeting of the American Society of Human Genetics
    • Place of Presentation
      San Diego Convention Center, San Diego, CA, USA
    • Year and Date
      2014-10-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Early drug responses that are followed by an acquired drug resistance in non-small cell lung cancer cells exposed to gefitinib.2014

    • Author(s)
      Takahashi M, Fukuoka M, and Hohjoh H.
    • Organizer
      64rd Annual Meeting of the American Society of Human Genetics
    • Place of Presentation
      San Diego Convention Center, San Diego, CA, USA
    • Year and Date
      2014-10-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] デジタルPCRを利用した新しい研究の可能性2014

    • Author(s)
      北條浩彦
    • Organizer
      ライフテクノロジーズ・オンラインセミナー
    • Place of Presentation
      ライフテクノロジーズジャパン株式会社本社(東京)
    • Year and Date
      2014-05-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] A corrective gene silencing by RNA interference to control over-expressed SNCA.2013

    • Author(s)
      Takahashi M, Suzuki M, Fujikake N, Murata M, Wada K, Nagai Y, and Hohjoh H.
    • Organizer
      63rd Annual Meeting of the American Society of Human Genetics
    • Place of Presentation
      Boston Convention & Exhibition Center, Boston, MA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 野生型α-シヌクレイン過剰発現に対する遺伝子発現量補正型RNAi誘導法の確立と有効性評価2013

    • Author(s)
      高橋理貴、鈴木マリ、藤掛伸宏、村田美穂、和田圭司、永井義隆、北條浩彦.
    • Organizer
      第36回日本分子生物学会大会
    • Place of Presentation
      神戸国際展示場(神戸)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 老化モデルマウスおよび正常加齢マウスにおけるmiR-29の発現上昇とこれを介したコラーゲンタイプIVの発現低下2012

    • Author(s)
      高橋理貴、枝亜希子、福島達伸、北條浩彦
    • Organizer
      第36回日本分子生物学会大会
    • Place of Presentation
      福岡市、福岡国際会議場
    • Year and Date
      2012-12-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] Oncogenic EGFR allele specific inhibition by RNA interference for cancer therapy lacking adverse effects.2012

    • Author(s)
      Takahashi M, Chiyo T, Okada T, and Hohjoh H.
    • Organizer
      62^<nd> Annual Meeting of the American Society of Human Genetics
    • Place of Presentation
      Moscone Convention Center,サンフランシスコ市、カリフォルニア州、アメリカ合衆国
    • Year and Date
      2012-11-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] Disease-causing allele specific inhibition by RNA interference.2012

    • Author(s)
      Hohjoh H., Takahashi M., Ohnishi Y., Katagiri T., and Furuya H
    • Organizer
      8^<th> Annual Meeting the Oligonucleotide Therapeutics Society
    • Place of Presentation
      The Joseph B. Martin Conference Center, Harvard Medical School,ボストン市、マサチューセッツ州、アメリカ合衆国
    • Year and Date
      2012-10-30
    • Related Report
      2012 Annual Research Report
  • [Presentation] 発がん性EGFR遺伝子特異的RNAiノックダウンを用いた副作用のない抗がん治療法の開発2012

    • Author(s)
      北條浩彦
    • Organizer
      第4回NHO大牟田病院 臨床研究部セミナー
    • Place of Presentation
      大牟田市、国立病院機構大牟田病院
    • Year and Date
      2012-07-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] 進行性骨化性線維異形成症のiPS細胞を用いたアレル特異的RNAi(ASP-RNAi)と薬剤スクリーニング

    • Author(s)
      古谷博和、菅原三和、渡邊暁博、荒畑創、笹ヶ迫直一、藤井直樹、 高橋理貴、北條浩彦、江良択実.
    • Organizer
      第54回日本神経学会学術大会総会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Related Report
      2013 Annual Research Report
  • [Book] 医学のあゆみ2014

    • Author(s)
      北條浩彦
    • Total Pages
      1
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2014 Annual Research Report
  • [Book] 原理からよくわかるリアルタイムPCR完全実験ガイド(編集:北條浩彦)2013

    • Author(s)
      北條浩彦
    • Total Pages
      34
    • Publisher
      羊土社
    • Related Report
      2013 Annual Research Report
  • [Book] 原理からよくわかるリアルタイムPCR完全実験ガイド(編集:北條浩彦)2013

    • Author(s)
      高橋理貴、北條浩彦
    • Total Pages
      15
    • Publisher
      羊土社
    • Related Report
      2013 Annual Research Report
  • [Book] RNAiの原理. 遺伝子導入実験プロトコール(編集 : 仲嶋一範、北村義浩、竹内恒成)2012

    • Author(s)
      程久美子、北條浩彦
    • Total Pages
      3
    • Publisher
      羊土社
    • Related Report
      2012 Annual Research Report
  • [Book] siRNA, dsRNAの取扱いと導入の基本. 遺伝子導入実験プロトコール(編集 : 仲嶋一範、北村義浩、竹内恒成)2012

    • Author(s)
      北條浩彦
    • Total Pages
      4
    • Publisher
      羊土社
    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi