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The therapeutic strategy for amyotrophic lateral sclerosis by elucidation and removal of accumulated protein-cleaving factors

Research Project

Project/Area Number 16K09681
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionTeikyo University

Principal Investigator

TAKUMA Hiroshi  帝京大学, 医学部, 講師 (00326258)

Co-Investigator(Kenkyū-buntansha) 桜井 正樹  帝京大学, 医学部, 教授 (30162340)
郭 伸  東京大学, 大学院医学系研究科(医学部), 客員研究員 (40160981)
玉岡 晃  筑波大学, 医学医療系, 教授 (50192183)
塩谷 彩子  筑波大学, 医学医療系, 講師 (60622735)
前川 裕美  九州大学, 農学研究院, 講師 (80399683)
Research Collaborator KAMEDA Hiroshi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords筋萎縮性側索硬化症 / 皮質運動野 / TDP-43 / microRNA / mRNA / 酵母 / マイクロRNA / 断片化 / 前頭側頭型認知症 / siRNA / 部位特異性
Outline of Final Research Achievements

In amyotrophic lateral sclerosis (ALS), many accumulated proteins and disease causative genes have been found, however the precise mechanism causing motor neuronal cell death has not been clarified, and we don’t get the path to ALS-treatment. In this study, TDP-43-related microRNAs obtained from model mice were not specifically altered in human ALS cerebral cortex motor cortex. In the comprehensive analysis of human motor area by microarray, we detected many microRNAs and mRNA candidates which expressions were changed, and a yeast system was also developed as a simple screening method for further study.

Academic Significance and Societal Importance of the Research Achievements

当初予定のin vivo電気穿孔法によるノックダウン・モデルマウスの開発には至らなかったが、ヒト脳におけるmicroRNAを含む遺伝子発現の網羅的データを得ることができた。これらの候補遺伝子の中には、ALSにおける神経変性の中核となる運動野において特異的に変化するものが多く含まれている。酵母による簡便なスクリーニング系も開発しており、今後の解析を通じて運動ニューロン死の実行役が同定されることが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017 2016

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 6 results)

  • [Journal Article] Vestibular dysfunction as cortical damage with amyotrophic lateral sclerosis2019

    • Author(s)
      Nakamagoe Kiyotaka、Yamada Shiori、Kawakami Rio、Miyake Zenshi、Tozaka Naoki、Okune Sho、Takeda Hayato、Koganezawa Tadachika、Tamaoka Akira
    • Journal Title

      Journal of the Neurological Sciences

      Volume: 397 Pages: 4-8

    • DOI

      10.1016/j.jns.2018.12.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TFEB-mediated Enhancement of the Autophagy-lysosomal Pathway Dually Modulates the Process of Amyloid β-Protein Generation in Neurons.2019

    • Author(s)
      Yamamoto F, Taniguchi K, Mamada N, Tamaoka A, Kametani F, Lakshmana MK, Araki W.
    • Journal Title

      Neuroscience. 2

      Volume: 402 Pages: 11-22

    • DOI

      10.1016/j.neuroscience.2019.01.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential innervation within a transverse plane of spinal gray matter by sensorimotor cortices, with special reference to the somatosensory cortices2019

    • Author(s)
      Kameda Hiroshi、Murabe Naoyuki、Odagaki Kaoru、Mizukami Hiroaki、Ozawa Keiya、Sakurai Masaki
    • Journal Title

      Journal of Comparative Neurology

      Volume: in press Issue: 8 Pages: 1401-1415

    • DOI

      10.1002/cne.24626

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ADAR2-dependent A-to-I RNA editing in the extracellular linear and circular RNAs.2018

    • Author(s)
      Hosaka T, Yamashita T, Teramoto S, Hirose N, Tamaoka A, Kwak S
    • Journal Title

      Neurosci Res.

      Volume: 印刷中 Pages: 48-57

    • DOI

      10.1016/j.neures.2018.11.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular epidemiological study of familial amyotrophic lateral sclerosis in Japanese population by whole-exome sequencing and identification of novel HNRNPA1 mutation2018

    • Author(s)
      Hiroya Naruse Hiroyuki Ishiura Jun Mitsui Hidetoshi Date Yuji Takahashi Takashi Matsukawa Masaki Tanaka Akiko Ishii Akira Tamaoka Keiichi Hokkoku Masahiro Sonoo Mari Segawa Yoshikazu Ugawa Koichiro Doi 3 more Shoji Tsuji
    • Journal Title

      Neurobiology of Aging.

      Volume: 61 Pages: 255.e9-255.e16

    • DOI

      10.1016/j.neurobiolaging.2017.08.030

    • URL

      https://pure.teikyo.jp/en/publications/356e2c71-cb9d-460b-8131-b9dcee0f7f06

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effect of truncation on prion-like properties of α-synuclein.2018

    • Author(s)
      Terada T, Suzuki G, Nonaka T, Kametani F, Tamaoka A, and Hasegawa M.
    • Journal Title

      J Biol Chem

      Volume: 293 Issue: 36 Pages: 13910-13920

    • DOI

      10.1074/jbc.ra118.001862

    • NAID

      120007133755

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy2018

    • Author(s)
      Ishiura Hiroyuki、Doi Koichiro、Mitsui Jun、Yoshimura Jun、Matsukawa Miho Kawabe、Takahashi Yuji、Date Hidetoshi、Matsukawa Takashi、Shimizu Jun、Koh Kishin、Takiyama Yoshihisa、Goto Jun、Morishita Shinichi、Tsuji Shoji
    • Journal Title

      Nature Genetics

      Volume: 50 Issue: 4 Pages: 581-590

    • DOI

      10.1038/s41588-018-0067-2

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell death cascade and molecular therapy in ADAR2-deficient motor neurons of ALS.2018

    • Author(s)
      Yamashita T, Kwak S
    • Journal Title

      Neurosci Res.

      Volume: 印刷中 Pages: 4-13

    • DOI

      10.1016/j.neures.2018.06.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Higher primate-like direct corticomotoneuronal connections are transiently formed in a juvenile subprimate mammal2018

    • Author(s)
      Murabe Naoyuki、Mori Takuma、Fukuda Satoshi、Isoo Noriko、Ohno Takae、Mizukami Hiroaki、Ozawa Keiya、Yoshimura Yumiko、Sakurai Masaki
    • Journal Title

      Scientific Reports

      Volume: - Issue: 1 Pages: 16536-16536

    • DOI

      10.1038/s41598-018-34961-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mediolateral and dorsoventral projection patterns of cutaneous afferents within transverse planes of the mouse spinal dorsal horn2018

    • Author(s)
      Odagaki Kaoru、Kameda Hiroshi、Hayashi Toshihiro、Sakurai Masaki
    • Journal Title

      Journal of Comparative Neurology

      Volume: 527 Issue: 5 Pages: 972

    • DOI

      10.1002/cne.24593

    • URL

      https://localhost/en/publications/fa316f01-e24d-4c40-913f-c51258a7019f

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutation-induced loss of APP function causes GABAergic depletion in recessive familial Alzheimer's disease : analysis of Osaka mutation-knockin mice2017

    • Author(s)
      Umeda Tomohiro、Kimura Tetsuya、Yoshida Kayo、Takao Keizo、Fujita Yuki、Matsuyama Shogo、Sakai Ayumi、Yamashita Minato、Yamashita Yuki、Ohnishi Kiyouhisa、Suzuki Mamiko、Takuma Hiroshi、Miyakawa Tsuyoshi、Takashima Akihiko、Morita Takashi、Mori Hiroshi、Tomiyama Takami
    • Journal Title

      Acta Neuropathol Commun

      Volume: 5 Issue: 1 Pages: 59

    • DOI

      10.1186/s40478-017-0461-5

    • NAID

      120006371271

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2019593

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] iPSC-based drug repositioning identifies Src/c-Abl as a therapeutic target for ALS motor neurons2017

    • Author(s)
      Imamura K, Izumi Y, 他24名, Hosokawa M, Akiyama H, Ayaki T, Ito H, Takahashi R, Yamanaka S, Inoue H
    • Journal Title

      Science Translational Medicine

      Volume: 9 Issue: 391 Pages: 391-391

    • DOI

      10.1126/scitranslmed.aaf3962

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Third nerve palsy due to local inflammation associated with vascular compression: A case series.2016

    • Author(s)
      Shimizu M, Tozaka N, Ishii A, Mamada N, Terada M, Takuma H, Tamaoka A
    • Journal Title

      J Neurol Sci.

      Volume: 367 Pages: 365-7

    • DOI

      10.1016/j.jns.2016.06.048

    • Related Report
      2016 Research-status Report
    • Peer Reviewed

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Published: 2016-04-21   Modified: 2020-03-30  

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