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Lab Introduction(2017)

This laboratory has started since 2013.
Our mission is to uncover the mechanisms of neurodegenerative disorder, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) to develop the viable therapy.

2024 group photo

2024 Apr. / Dr. Shinno, Ms. Noda, and Ms. Kato joined to our lab.

Study(DMF)

2024 Apr. / We reported that Dimetyl fumarate activates Nrf2 pathway in glial cells to reduce neuroinflammation in Alzheimer's disease model mice in Journal of Neuroinflammation.

2024 Hashimoto and Yanagisawa

2024 Mar. / Dr. Hashimoto was awarded Ph.D. in medicine, Ms. Yanagisawa was awarded a master degree in medical sciences.

Study(B6Balb)

2024 Feb. / We reported that variation of microglial activation derived from genetic backgrounds affects ALS progression in ALS in iScience.

Study(MAM-TBK1)

2023 Nov. / We reported that collapse of ER-mito contact site (MAM) induces TBK1 inactivation, resulting in deregulated stress response in ALS in PNAS.

Study(TDP-43monomer)

2023 Aug. / We reported that TDP-43 monomerization is a key mechanism of TDP-43 pathology in ALS in Sci Adv.

Study(cSOD1)

2023 May / We reported a species-specific aggregation mechanism of canine SOD1 in J Biol Chem.

Our Recent Activity

Our Past Activity in 2022

Our Past Activity in 2021

  • 2021/11/25
    AWARDGRANT Ms. Maekawa became an Interdisciplinary Frontier Fellow of Nagoya University. Dr. Hashimoto and Ms. SHimogawa became an Interdisciplinary Frontier Next Generation Researcher of Tokai National Higher Education and Research System (THERS).
  • 2021/11/25
    MEETING We gave presentations of our studies and organized symposiums as bellow:

    The 44th Annual Meeting of the Japan Neuroscience Society, joined with the 1st China-Japan-Korea (CJK) International Meeting (Jul. 28-31, Kobe Convention Center and online)
    Drs. Komine, Sobue, Watanabe, Oiwa, Horiuchi, Ms. Wang, and Mr. Sakai gave presentations.

    Pan-Asia Consortium for Treatment & Research (PACTALS) 2021 (9/17-18, online)
    Prof. Yamanaka talked and chaired the symposium.
    Drs. Watanabe, Horiuchi, Hashimoto, and Mr. Sakai gave presentations.

    Dr. Hashimoto gave an presentation in the 164th Anuual meeting of the Japanese Society of Veterinary Science .

    The 33rd Annual Meeting of the Japanese Society for Neuroimmunology (10/21-22, online)
    Prof. Yamanaka co-chaired a symposium entitled "Advances in basic research on molecular pathology of neurological diseases" with Prof. Mineki Saito (Kawasaki Medicai Univ.).
    Dr. Komine gave an presentation.

    Prof. Yamanaka gave an invited talk in the 74th Anuual Meeting of the Japan Society of Neurovegetative Research (10/23, online).

    Prof. Yamanaka gave an presentation as a symposist in the 39th Anuual Meeting of Japanese Society of Neurological Therapeutics (10/28, Tsu, Mie).

    the 94th Annual Meeting of the Japanese Biochemical Society (11/3-5, online)
    Drs. Watanabe, and Hashimoto gave presentations.

  • 2021/10/1
    Ms. Maika Kato joined to our Lab.
  • 2021/6/24
    NEWRESEARCH Our paper is now open in The FASEB Journal.

    Research (MAMtracker)


    The mitochondria-associated membrane (MAM) is a functional subdomain of the endoplasmic reticulum membrane that tethers to the mitochondrial outer membrane and is essential for cellular homeostasis. However, it is still uncertain whether MAM disruption is a common pathology in ALS, mainly due to the absence of a simple, quantitative tool for monitoring the status of MAM. In this study, to examine the effects of various ALS-causative genes on MAM, we created the following two novel MAM reporters: MAMtracker-Luc and MAMtracker-Green. We suggest that MAM disruption is a common pathological feature in ALS using the MAMtrackers. Furthermore, we anticipate our MAMtrackers, which are suitable for high-throughput assays, to be valuable tools to understand MAM dynamics.


    Open Access
    Sakai S, Watanabe S, Komine O, Sobue A, and Yamanaka K
    Novel reporters of mitochondria-associated membranes (MAM), MAMtrackers, demonstrate MAM disruption as a common pathological feature in amyotrophic lateral sclerosis.
    The FASEB Journal (2021) e21688. DOI: 10.1096/fj.202100137R

  • 2021/4/1
    Dr. Kawade (Assistant Professor) and Ms. Nagata (Technical Staff) joined to our lab.

    Group Photo(2021/4)
    Our Lab Group Photo in 2021.

  • 2021/2/6
    MEETING Ms. Horiuchi, Mr. Hashimoto, Ms. Maekawa and Mr. Sakai gave presentations in 2nd CIBoG retreat/13th Nagoya Global retreat(Feb 6th, online). Ms. Maekawa won a best poster presentation award in the meeting.

    Award for maekawa
    In our Lab. Dr. Yamanaka, Ms. Maekawa and Dr. Sobue from the right.

  • 2021/2/1
    RESEARCH Our work is now open in Acta Neuropathologica Communications:

    Summary (AD microglia)


    In this study, we analyzed gene expression profiles of microglia isolated by magnetic activated cell sorting (MACS) from three mouse models for neurodegenerative diseases: AppNL-G-F/NL-G-F mice that display an amyloid pathology, rTg4510 mice with tauopathy, and SOD1(G93A) mice with motor neurodegeneration by RNA-sequencing. Despite robust neuroinflammation with microglial responses in all mouse models, AppNL-G-F/NL-G-F mice do not show neuronal death, whereas rTg4510 and SOD1(G93A) mice show a substantial loss of neurons. We found that the reduction of homeostatic microglial genes was correlated with severity of neurodegeneration, whereas DAM genes were uniformly upregulated in all mouse models. Moreover, in human precuneus with early AD pathology, reduced gene expressions of microglia and oligodendrocytes were observed, although DAM genes were not upregulated. Results from the present study indicate a correlation between glial phenotypes and severity of neurodegeneration, and also provide important resources to better understand the role of glial dysfunction in progression of Alzheimer's disease.

    Open Access
    Sobue A, Komine O, Hara Y, Endo F, Mizoguchi H, Watanabe S, Murayama S, Saito T, Saido T, Sahara N, Higuchi M, Ogi T and Yamanaka K
    外部リンク "Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer’s disease."
    Acta Neuropathol Commun (2021) 9: 1. DOI: 10.1186/s40478-020-01099-x

    PDF file Press release from Nagoya Univ

Our Past Activity in 2020

Our Past Activity in 2019

  • 2019/10/1
    Ms. Yuri Banno and Chitose Imai have joined to our Lab as students of Training for Medical Research in 2019.

    集合写真(2019)
    2019 Oct / Welcome party at our lab.

  • 2019/7/31
    RESEARCHOur paper is now open in Acta Neuropathologica Communications.

    Abstract(TDP-ΔC)

    We investigated the pathological role of TDP-43 N-terminal fragments, which is also accumulated in ALS patients as well as full-length TDP-43 and TDP-43 C-terminal fragments. We produced TDP-ΔC knock-in mice, expressing TDP-43 N-terminal fragments at the similar level of endogenous TDP-43 (left panel). This mice showed age-dependent motor dysfunction (right panel) with reduced C-boutons, large cholinergic synapses on motor neurons, and Notch1-Akt signaling pathway (middle panel, arrowheads indicate C-boutons). Our data uncovered a detrimental role of N-terminal TDP-43 fragments in ALS pathology in mice, associated with suppression of Akt surviving signal.

    Open Access
    Nishino K, Watanabe S, Shijie J, Murata Y, Oiwa K, Komine O, Endo F, Tsuiji H, Abe M, Sakimura K, Mishra A, Yamanaka K
    外部リンク "Mice deficient in the C-terminal domain of TAR DNA-binding protein 43 develop age-dependent motor dysfunction associated with impaired Notch1-Akt signaling pathway."
    Acta Neuropathologica Communications (2019) 7(1): 118. DOI: 10.1186/s40478-019-0776-5

  • 2019/7/31
    MEETING Prof. Yamanaka, Drs. Komine, Sobue, Watanabe, and Oiwa gave their presentations in Neuro 2019 (2019/7/25-28, Niigata).
  • 2019/4/1
    Three new graduate students have joined to our Lab: Mr. Sakai (M1), Ms. Shimogawa (D1), and Dr. Horiuchi (MD, D1).

    Group Photo(2019/4)
    Group photo of our current laboratory members (2019 Apr in Higashi-yama Campus, Nagoya University).

  • 2019/2/12
    MEETING Dr. Watanabe gave a presentation in Japan-UK Neuroscience Symposium organized by AMED, Japan (Kisarazu, Chiba).
  • 2019/2/1
    Ms. Miyoshi has joined to our lab as a Technical Staff.

Our Past Activity in 2018

  • 2018/12/1
    MEETING Prof. Yamanaka, Dr. Komine, and Dr. Sobue gave presentations in 23rd Glia meetings (Prof. Yamanaka talked as an invited speaker).
  • 2018/12/1
    Ms. Banno, an undergraduate student (B1), has joined to our lab.
  • 2018/11/7
    MEETING Prof. Yamanaka & Dr. Komine gave presentations in Neuroscience 2018 (San-Diego, CA, USA).
  • 2018/10/4
    MEETING Dr. Sobue gave a presentation in 37th Annual Meeting of Japan Society for Dementia Research (Oct 12-14 in Sapporo).
  • 2018/10/1
    Mr. Iida & Mr. Natsume have joined to our lab in Basic Science Sminar. In addition, Ms. Wang has joined to our lab as a research student.

    Welcome party(2018/10)
    Group Photo at the welcome party.

  • 2018/9/12
    Mr. Sugiyama & Ms. Kinoshita joined to our laboratory couse.

    lab course(2018/9)
    At our laboratory. Dr. Watanabe, Ms. Kinoshita, Mr. Sugiyama, and Prof. Yamanaka from the left.

  • 2018/9/12
    PRESS Dr. Yamanaka got an interview on Council of Research Institute and Centers of Japanese National Universities.

    Interview Photo(2018)

  • 2018/7/30
    MEETING Prof. Yamanaka talked as an invited speaker in Summer Lecture of Neurology in Niigata (Niigata University).
  • 2018/5/17
    AWARD Mr. Inami won a Medical Student Research Award of Nagoya University 2018.
  • 2018/4/6
    RESEARCH Our paper is now open in Cell Death & Differentiation.

    Research(TRIF-ALS)

    We reported that innate immune TRIF pathway plays an important role in protecting a microenvironment surrounding motor neurons by eliminating aberrantly activated astrocytes.

    Open Access
    Komine O, Yamashita H, Fujimori-Tonou N, Koike M, Jin S, Moriwaki Y, Endo F, Watanabe S, Uematsu S, Akira S, Uchiyama Y, Takahashi R, Misawa H, Yamanaka K
    Link "Innate immune adaptor TRIF deficiency accelerates disease progression of ALS mice with accumulation of aberrantly activated astrocytes."
    Cell Death & Differentiation in press doi:10.1038/s41418-018-0098-3.

  • 2018/4/6
    Dr. Sobue has joined to our lab as an assistant professor.