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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.

Research(MAMTracker)

2021 Jun. / Our paper is now open in The FASEB Journal.

Group Photo(2021)

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

Maekawa PosterPresentationAward

2021 Feb. / Ms. Maekawa won the poster presentation award in 2nd CIBoG retreat.

Study(microglia RNA-seq)

2021 Jan. / Our paper is now open in Acta Neuropathologica Communications.

Sobue Award

2020 Nov. / Dr. Sobue won the oral presentation award in the 39th Annual Meeting of Japan Society for Dementia Research.

Study(TDP-43 agg screening)

2020 Sep. / Our paper is now open in Cell Death & Disease.

Our Recent Activity

  • 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.

  • 2020/11/28
    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

  • 2020/11/28
    MEETING Dr. Sobue won an oral presentation award in the 39th Annual Meeting of Japan Society for Dementia Research (11/26-28, Online and Nagoya International Conference Center).
    Prof. Yamanaka co-organized a symposium entitled as "Neuroinflammation in Alzheimer's disease" with Prof. Ikuo Tooyama (Shiga University of Medical Science). Ms. Wang and Ms. Shimogawa also gave poster presentations in the meeting.

    at the party
    Dr. Sobue (left), who won the prize, and Prof. Dr. Yamanaka (right).

  • 2020/10/27
    RESEARCH Our work is now open in Cell Death & Disease :

    Summary(AggScreeningTDP-43)


    We found that microtubule-related proteins (MRPs) and RNA-binding proteins (RBPs) co-aggregated with TDP-43. These two types of proteins sequestered TDP-43 through independent mechanisms; a liquid-liquid phase separation (LLPS) and an aggresome formation. Moreover, in sporadic ALS patients, approximately half of skein-like TDP-43 inclusions were co-localized with HDAC6, but round and granular type inclusion were not. Our findings suggest that two pathways (LLPS and aggresomes) independently induce TDP-43 aggregation and that both the mechanisms are involved in TDP-43 pathology in sporadic ALS patients. The findings will lead to a novel therapeutic strategy for ALS.

    Watanabe S, Inami H, Oiwa K, Murata Y, Sakai S, Komine O, Sobue A, Iguchi Y, Katsuno M, Yamanaka K
    outer link "Aggresome formation and liquid–liquid phase separation independently induce cytoplasmic aggregation of TAR DNA-binding protein 43."
    Cell Death Dis (2020) 11: 909. DOI: 10.1038/s41419-020-03116-2

    PDF file Press release from Nagoya Univ.

  • 2020/10/27
    MEETING We gave presentations in the symposiums/conferences listed below:

    The 43rd Annual Meeting of the Japan Neuroscience Society (7/29-8/1, Online Meeting)
    ・Prof. Yamanaka co-organized the symposium: "Infrastructures of the brain that support logistics solutions in health and disease" with Dr. Yu Hayashi (WPI-IIIS, Tsukuba Univ.).
    ・Drs. Komine, Sobue, and Watanabe gave oral/poster presentations.

    61st Annual Meeting of the Japanese Society of Neurology (8/31-9/2, Okayama Convention Center and Online Meeting)
    ・Prof. Yamanaka gave an presentation in the symposium.
    ・Dr. Oiwa gave an presentation.

    The 63rd Annual Meeting of the Japanese Society for Neurochemistry (9/10-9/12, Online Meeting)
    ・Prof. Yamanaka co-organized the symposium with Dr. Minako Ito (Kyusyu Univ.) and gave an presentation as a symposiast.

    The 93rd Annual Meeting of the Japanese Biochemical Society (9/14-9/16, Online Meeting)
    ・Prof. Yamanaka co-organized the symposium: "Brain Infrastructure: A new logistic system of the brain in health and disease." with Dr. Kaoru Yamada (Univ. Tokyo).
    ・Drs. Komine and Watanabe gave presentations as symposiasts.

    The 32nd Annual Meeting of the Japanese Society for Neurochemistry (10/1-10/2, Online Meeting)
    ・Prof. Yamanaka co-chaired the symposium: "microglia: frontiers in clinical and basic research" with Dr. Hideyuki Takeuchi (Yokohama City Univ.) and gave an presentation.

  • 2020/10/1
    Mr. Sakakibara and Ms. Kinoshita (both B3) joined in our laboratory.
  • 2020/8/28
    RESEARCH Our collaborative work with Dr. Hasnain's team in Univ. Liverpool in EBioMedicine :

    Summary(Ebselen)


    A group of researchers from the Universities of Liverpool (UK) and Nagoya (Japan) have shown that a Selenium based drug-molecule called ebselen and a number of other novel compounds developed at Liverpool can change many of the toxic characteristics of a protein, superoxide dismutase (SOD1), which causes some cases of ALS, also known as motor neuron disease as well as Lou Gehrig’s disease.

    Amporndanai K, Rogers M, Watanabe S, Yamanaka K, O’Neill P. M., Hasnain S. S.
    外部リンク "Novel Selenium-based compounds with therapeutic potential for SOD1-linked Amyotrophic Lateral Sclerosis."
    EBioMed (2020) 59: 102980. DOI: 10.1016/j.ebiom.2020.102980

    PDF file Press release from Nagoya Univ.

  • 2020/4/1
    RESEARCH Our collaborative works are now open in Neurochem Int and Cell:

    Sugiyama M, Banno R, Yaginuma H, Taki K, Mizoguchi A, Tsunekawa T, Onoue T, Takagi H, Ito Y, Iwama S, Goto M, Suga H, Komine O, Yamanaka K, Arima H.
    外部リンク "Hypothalamic glial cells isolated by MACS reveal that microglia and astrocytes induce hypothalamic inflammation via different processes under high-fat diet conditions."
    Neurochem Int (2020) 136: 104733. DOI: 10.1016/j.neuint.2020.104733

    Nakazawa Y, Hara Y, Oka Y, Komine O, van den Heuvel D, Guo C, Daigaku Y, Isono M, He Y, Shimada M, Kato K, Jia N, Hashimoto S, Kotani Y, Miyoshi Y, Tanaka M, Sobue A, Mitsutake N, Suganami T, Masuda A, Ohno K, Nakada S, Mashimo T, Yamanaka K, Luijsterburg MS, Ogi T
    外部リンク "Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair."
    Cell (2020) 180(6): 1228-1244.e24. DOI: 10.1016/j.cell.2020.02.010

  • 2020/4/1
    Dr. Hashimoto & Ms. Maekawa have joined our lab.

    group photo(2020/4)
    Our Lab members in 2020.

  • 2020/1/24
    RESEARCHOur paper is now open in Molecular Brain.

    研究紹介M337V-KI abstract

    TDP-43 is a key molecule in ALS pathology. Transgenic mice models of TDP-43 suffer from acute toxicity induced by excess amounts of TDP-43 proteins. Therefore, we established TDP-43(M337V) knock-in mice by genome editing using Cas9 (A). The knock-in mice showed RNA deregulation dependent on TDP-43 gain-of-function mechanism (B), similar to the previous studies (White et al. (2018) Nat Neurosci etc.), but no motor neuron degeneration was observed (C). These results suggest that additional conformational change of TDP-43 protein may be needed to develop TDP-43 pathology.

    Open Access
    Watanabe S, Oiwa K, Murata Y, Komine O, Sobue A, Endo F, Takahashi E and Yamanaka K
    外部リンク "ALS-linked TDP-43M337V knock-in mice exhibit splicing deregulation without neurodegeneration."
    Molecular Brain (2020) 13: 8. DOI: 10.1186/s13041-020-0550-4

  • 2020/1/24
    MEETINGWe gave presentations in the meetings listed below:

    ・Dr. Sobue: 2019 Nov The 38th Annual Meeting of Japan Society for Dementia Research
    ・Prof. Yamanaka, Dr. Watanabe: 2019 Dec 30th International Symposium on ALS/MND (Perth, Australia)

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.