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Mechanisms underlying neuronal dysfunction and degeneration caused by loss of presynaptic mitochondria

Research Project

Project/Area Number 15K06712
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurophysiology / General neuroscience
Research InstitutionTokyo Metropolitan University

Principal Investigator

Ando Kanae  首都大学東京, 理工学研究科, 准教授 (40632500)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsミトコンドリア / 神経細胞死 / 加齢 / 軸索輸送 / エネルギー代謝 / 神経変性疾患 / CaMKII / 神経細胞 / 細胞内局在 / ATP / 軸索 / 遺伝子発現
Outline of Final Research Achievements

Brain nerve cells extend long processes to communicate with other cells. The contact sites are called synapses and demand energy supply to function. To meet the energy demands, mitochondria, tiny powerhouses in the cell, are transported from the cell body of the nerve cells. Depletion of mitochondria from the cells disrupts neuronal functions and eventually causes neuronal death. However, how the loss of synaptic mitochondria leads to neuronal death is not known. To elucidate the underlying molecular mechanisms, we used transgenic fruit fly to deplete mitochondria from synapses. We identified several molecules that are involved in neuronal dysfunction and cell loss triggered by loss of synaptic mitochondria. Since the loss of synaptic mitochondria is associated with neurodegenerative diseases such as Alzheimer’s disease, these findings may lead to development of a cure.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (23 results)

All 2018 2017 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Int'l Joint Research: 8 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Integrated biology approach reveals molecular and pathological interactions among Alzheimer’s Aβ42, Tau, TREM2, and TYROBP in Drosophila models2018

    • Author(s)
      Sekiya Michiko、Wang Minghui、Fujisaki Naoki、Sakakibara Yasufumi、Quan Xiuming、Ehrlich Michelle E.、De Jager Philip L.、Bennett David A.、Schadt Eric E.、Gandy Sam、Ando Kanae、Zhang Bin、Iijima Koichi M.
    • Journal Title

      Genome Medicine

      Volume: 10 Issue: 1 Pages: 26-26

    • DOI

      10.1186/s13073-018-0530-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of synaptic mitochondria and dementia.2017

    • Author(s)
      Oka, M., Iijima, K.M. and Ando, K.
    • Journal Title

      実験医学

      Volume: 35(12) Pages: 182-185

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Ca2+/calmodulin-dependent protein kinase II promotes neurodegeneration caused by tau phosphorylated at Ser262/356 in a transgenic Drosophila model of tauopathy2017

    • Author(s)
      Oka Mikiko、Fujisaki Naoki、Maruko-Otake Akiko、Ohtake Yosuke、Shimizu Sawako、Saito Taro、Hisanaga Shin-Ichi、Iijima Koichi M、Ando Kanae
    • Journal Title

      The Journal of Biochemistry

      Volume: 162 Issue: 5 Pages: 335-342

    • DOI

      10.1093/jb/mvx038

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EDEM Function in ERAD Protects against Chronic ER Proteinopathy and Age-Related Physiological Decline in Drosophila2017

    • Author(s)
      Sekiya Michiko、Maruko-Otake Akiko、Hearn Stephen、Sakakibara Yasufumi、Fujisaki Naoki、Suzuki Emiko、Ando Kanae、Iijima Koichi M.
    • Journal Title

      Developmental Cell

      Volume: 41 Issue: 6 Pages: 652-664

    • DOI

      10.1016/j.devcel.2017.05.019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tau phosphorylation at Alzheimer's disease-related Ser356 contributes to tau stabilization when PAR-1/MARK activity is elevated.2016

    • Author(s)
      Ando K, Oka M, Ohtake M, Hayashishita M, Shimizu S, Hisanaga S, Iijima KM
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 478 (2) Issue: 2 Pages: 929-934

    • DOI

      10.1016/j.bbrc.2016.08.053

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Stabilization of microtubule-unbound tau via tau phosphorylation at Ser262/356 by Par-1/MARK contributes to augmentation of AD-related phosphorylation and Aβ42-induced tau toxicity.2016

    • Author(s)
      Ando, K.*, Maruko-Otake, A., Ohtake, Y., Hayashishita, M., Sekiya, M., and Iijima, K. M.
    • Journal Title

      PLoS Genetics

      Volume: 12(3) Issue: 3 Pages: e1005917-e1005917

    • DOI

      10.1371/journal.pgen.1005917

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Increasing glucose uptake in Drosophila brain neurons suppresses the reduction in ATP levels and rescues the decline in neuronal function during aging2018

    • Author(s)
      M. Oka , E. Suzuki , S. Hisanaga , KM. Iijima , K Ando
    • Organizer
      59th Annual Drosophila Research Conference, April 2018, Philadelphia
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of CaMKII in neurodegeneration caused by depletion of presynaptic mitochondria2018

    • Author(s)
      K. Shinno , M. Oka , S. Hisanaga , E. Suzuki , K.M. Iijima , K. Ando
    • Organizer
      59th Annual Drosophila Research Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidating pathological cascades in tauopathies by using Drosophila models2017

    • Author(s)
      Kanae Ando
    • Organizer
      International Conference of the Genetics Society of Korea (ICGSK) 2017’ Seoul, Korea
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ‘Increasing glucose uptake suppresses age-dependent reductions in ATP levels in brain neurons and behavioral deficits in Drosophila’2017

    • Author(s)
      Mikiko Oka, Emiko Suzuki, Hiromi Imamura, Shin-ichi Hisanaga, Koichi M. Iijima and Kanae Ando
    • Organizer
      ASCB/EMBO 2017 meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CaMKII enhances tau-mediated neurodegeneration downstream of tau phosphorylation in transgenic Drosophila models of tauopathy.2017

    • Author(s)
      Ando*, K., Oka, M., Maruko-Otake, A., Ohtake, Y., Sekiya, M., Hisanaga, S., Iijima, K.M.
    • Organizer
      The 4th Asia-Pacific Drosophila Research Conference, Suita, Osaka, Japan, May 10, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanisms underlying age-dependent reduction in ATP levels in Drosophila brain neurons.2017

    • Author(s)
      Oka, M., Suzuki, E., Hisanaga, S., Iijima, K.M., Ando, K.
    • Organizer
      The 4th Asia-Pacific Drosophila Research Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanisms underlying age-dependent reduction in ATP levels in Drosophila brain neurons2017

    • Author(s)
      Mikiko Oka, Emiko Suzuki, Shin-Ichi Hisanaga, Koichi Iijima, and Kanae Ando
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 軸索ミトコンドリアの欠乏によるショウジョウバエ視神経軸索変性における CaMKIIの役割2017

    • Author(s)
      真野 叶子、岡 未来子、浅田 明子、斎藤 太郎、久永 眞市、鈴木 えみ子、飯島 浩一, 安藤 香奈絵
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] “Reduction in ATP levels in the axon during aging and the role of mitochondrial distribution.”2016

    • Author(s)
      Oka, M., Suzuki, E., Hisanaga, S.-i., Iijima, KM, and Ando., K.
    • Organizer
      59th Annual Meeting of The Japanese Society for Neurochemistry
    • Place of Presentation
      福岡
    • Related Report
      2016 Research-status Report
  • [Presentation] “Reduction in ATP levels in the axon during aging and the role of mitochondrial distribution.” (selected for oral presentation at nano symposium)2016

    • Author(s)
      Oka,M., Suzuki, E., Hisanaga, S., Iijima, KM, and Ando., K.
    • Organizer
      46th annual meeting of Society for Neuroscience
    • Place of Presentation
      San Diego, USA
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sustained activation of CaMKII caused by depletion of mitochondria from the axon enhances tau toxicity. (selected for oral presentation at nano symposium)2016

    • Author(s)
      Ando, K., Maruko-Otake, A., Hayashishita, M., Oka, M., Ohtake, Y., Sekiya, M., Saito, T., Hisanaga, S., and Iijima, KM.
    • Organizer
      46th annual meeting of Society for Neuroscience
    • Place of Presentation
      San Diego, USA
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] “Sustained activation of CaMKII mediates enhancement of tau toxicity caused by depletion of mitochondria from the axon”2015

    • Author(s)
      Motoki Hayashishita*1, Akiko Maruko-Otake2, Yosuke Ohtake3, Michiko Sekiya4, Koichi M. Iijima4 and Kanae Ando1
    • Organizer
      38th Annual meeting for the Molecular Biology Society in Japan,
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] “Sustained activation of CaMKII mediates neurodegeneration caused by depletion of axonal mitochondria”2015

    • Author(s)
      Mikiko Oka*1, Akiko Maruko-Otake2, Yosuke Ohtake2, Naoya Yamaguchi1, Michiko Sekiya3, Koichi M. Iijima3, Kanae Ando1
    • Organizer
      38th Annual meeting for the Molecular Biology Society in Japan
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] “Pathological stabilization of tau through phosphorylation at Ser262/356 by Par-1/MARK contributes to abnormal metabolism and toxicity of tau caused by Aβ42”2015

    • Author(s)
      Ando, K.*, Maruko-Otake, A., Ohtake, Y., Hayashishita, M., Sekiya, M. and Iijima, K. M.Nagoya, Japan
    • Organizer
      The 1st Internatinal Symposium of “Brain Protein Aging and Dementia Control”,
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] “Tau phosphorylation via microtubule affinity regulating kinase MARK/PAR1 as an initial step in the pathological cascade leading to neurodegeneration”2015

    • Author(s)
      Ando, K. *, Hayashishita, M., Oka,M., Maruko-Otake, A., Ohtake, Y., Iijima, K.M.
    • Organizer
      The 58th Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      埼玉
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 「Microtubule-affinity-regulating-kinase (MARK)/PAR-1によるタウのリン酸化は異常タウの蓄積を引き起こす」2015

    • Author(s)
      安藤 香奈絵
    • Organizer
      2015 タウ研究ミーティング
    • Place of Presentation
      京都
    • Year and Date
      2015-09-03
    • Related Report
      2015 Research-status Report
    • Invited
  • [Book] Neuromethods, Chapter: Electron microscopy of the brains of Drosophila Models of Alzheimer’s disease. DOI 10.1007/7657_2015_75,2016

    • Author(s)
      Ando, K.*, Hearn, A., Suzuki, E., Maruko-Otake, A., Sekiya, M., and Iijima, K.M.
    • Total Pages
      19
    • Publisher
      Springer
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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