Furukawa, Yoshiaki

写真a

Affiliation

Faculty of Science and Technology, Department of Chemistry (Yagami)

Position

Professor

Related Websites

External Links
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Research Areas 【 Display / hide 】

  • Life Science / Functional biochemistry

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Research Keywords 【 Display / hide 】

  • Neurodegenerative disease

  • Amyotrophic lateral sclerosis

  • Intracellular copper transport

  • Metallochaperone protein

  • Metalloprotein

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Papers 【 Display / hide 】

  • Cysteine residues in Cu,Zn-superoxide dismutase are essential to toxicity in Caenorhabditis elegans model of amyotrophic lateral sclerosis

    Ogawa, Mariko, Shidara, Hisashi, Oka, Kotaro, Kurosawa, Masaru, Nukina, Nobuyuki, Furukawa, Yoshiaki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 463 ( 4 ) 1196 - 1202 2015.08

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0006-291X

  • Conformational Disorder of the Most Immature Cu, Zn-Superoxide Dismutase Leading to Amyotrophic Lateral Sclerosis

    Furukawa, Yoshiaki, Anzai, Itsuki, Akiyama, Shuji, Imai, Mizue, Cruz, Fatima Joy C., Saio, Tomohide, Nagasawa, Kenichi, Nomura, Takao, Ishimori, Koichiro

    JOURNAL OF BIOLOGICAL CHEMISTRY 291 ( 8 ) 4144 - 4155 2016.02

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0021-9258

  • A molecular mechanism realizing sequence-specific recognition of nucleic acids by TDP-43

    Furukawa, Yoshiaki, Suzuki, Yoh, Fukuoka, Mami, Nagasawa, Kenichi, Nakagome, Kenta, Shimizu, Hideaki, Mukaiyama, Atsushi, Akiyama, Shuji

    SCIENTIFIC REPORTS 6   4144 - 4155 2016.02

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2045-2322

  • Novel oxindole compounds inhibit the aggregation of amyloidogenic proteins associated with neurodegenerative diseases

    Kimura S., Kamishina H., Hirata Y., Furuta K., Furukawa Y., Yamato O., Maeda S., Kamatari Y.O.

    Biochimica et Biophysica Acta - General Subjects (Biochimica et Biophysica Acta - General Subjects)  1866 ( 5 )  2022.05

    ISSN  03044165

    　View Summary

    Amyloidogenic proteins form aggregates in cells, thereby leading to neurodegenerative disorders, including Alzheimer's and prion's disease, amyotrophic lateral sclerosis (ALS) in humans, and degenerative myelopathy (DM) and cognitive dysfunction in dogs. Hence, many small-molecule compounds have been screened to examine their inhibitory effects on amyloidogenic protein aggregation. However, no effective drug suitable for transition to clinical use has been found. Here we examined several novel oxindole compounds (GIF compounds) for their inhibitory effects on aggregate formation of the canine mutant superoxide dismutase 1 (cSOD1 E40K), a causative mutation resulting in DM, using Thioflavin-T fluorescence. Most GIF compounds inhibited the aggregation of cSOD1 E40K. Among the compounds, GIF-0854-r and GIF-0890-r were most effective. Their inhibitory effects were also observed in cSOD1 E40K-transfected cells. Additionally, GIF-0890-r effectively inhibited the aggregate formation of human SOD1 G93A, a causative mutation of ALS. GIF-0827-r and GIF-0856-r also effectively inhibited aggregate formation of human prion protein (hPrP). Subsequently, the correlation between their inhibitory effects on cSOD1 and hPrP aggregation was shown, indicating GIF compounds inhibited the aggregate formation of multiple amyloidogenic proteins. Conclusively, the novel oxindole compounds (GIF-0827-r, GIF-0854-r, GIF-0856-r, and GIF-0890-r) are proposed as useful therapeutic candidates for amyloidogenic neurodegenerative disorders.

  • Metal distribution in Cu/Zn-superoxide dismutase revealed by native mass spectrometry

    Tajiri M., Aoki H., Shintani A., Sue K., Akashi S., Furukawa Y.

    Free Radical Biology and Medicine (Free Radical Biology and Medicine)  183   60 - 68 2022.04

    ISSN  08915849

    　View Summary

    Cu/Zn-superoxide dismutase (SOD1) is a homodimer with two identical subunits, each of which binds a copper and zinc ion in the native state. In contrast to such a text book case, SOD1 proteins purified in vitro or even in vivo have been often reported to bind a non-stoichiometric amount of the metal ions. Nonetheless, it is difficult to probe how those metal ions are distributed in the two identical subunits. By utilizing native mass spectrometry, we showed here that addition of a sub-stoichiometric copper/zinc ion to SOD1 led to the formation of a homodimer with a stochastic combination of the subunits binding 0, 1, and even 2 metal ions. We also found that the homodimer was able to bind four copper or four zinc ions, implying the binding of a copper and zinc ion at the canonical zinc and copper site, respectively. Such ambiguity in the metal quota and selectivity could be avoided when an intra-subunit disulfide bond in SOD1 was reduced before addition of the metal ions. Apo-SOD1 in the disulfide-reduced state was monomeric and was found to bind only one zinc ion per monomer. By binding a zinc ion, the disulfide-reduced SOD1 became conformationally compact and acquired the ability to dimerize. Based upon the results in vitro, we describe the pathway in vivo enabling SOD1 to bind copper and zinc ions with high accuracy in their quota and selectivity. A failure of correct metallation in SOD1 will also be discussed in relation to amyotrophic lateral sclerosis.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Presentations 【 Display / hide 】

  • Clinical and neuropathological study of an autopsied case of familial ALS with SOD1 mutation with very long survival

    Yo-ichi Takei, Kenya Oguchi, Takaaki Miyahira, Akiyo Hineo, Akinori Nakamura, Shinji Ohara, and Yoshiaki Furukawa

    The 68th Annual Meeting of the American Academy of Neurology (Vancouver, Canada) , 

    2016.04
    , 

    Poster presentation

  • 銅・亜鉛スーパーオキサイドディスムターゼの金属イオン結合状態を識別できる新規抗体の開発と筋萎縮性側索硬化症の病理解明への応用

    徳田　栄一、森崎　祐太、三澤　日出巳、渡邊　征爾、山中　宏二、古川　良明

    日本薬学会第136年会 (神奈川県・横浜市) , 

    2016.03
    , 

    Oral presentation (general)

  • タンパク質の熱変性を通じて理解する神経変性疾患の発症メカニズム

    安齋　樹、向山　厚、秋山　修志、古川　良明

    日本化学会第96春季年会 (京都府・京田辺市) , 

    2016.03
    , 

    Oral presentation (general)

  • 細胞内銅イオン輸送を可能にする銅シャペロンのドメイン構造

    福岡　真実、長野　功、古川　良明

    日本化学会第96春季年会 (京都府・京田辺市) , 

    2016.03
    , 

    Oral presentation (general)

  • 抗酸化酵素の活性発現を可能にする金属イオンの新たな獲得メカニズム

    小久保　鉄平、櫻井　靖之、古川　良明

    日本化学会第96春季年会 (京都府・京田辺市) , 

    2016.03
    , 

    Oral presentation (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 超硫黄化による銅シャペロン保護メカニズムの解明

    2024.04
    -
    2026.03

    学術変革領域研究(A), Principal investigator

  • 神経変性疾患の早期診断を指向した構造異常型タンパク質の極微量検出

    2022.06
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 挑戦的研究（萌芽）, Principal investigator

  • 加齢に伴うタンパク質の構造・機能変化とその病理学的役割の解明

    2022.04
    -
    2026.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(B), Principal investigator

  • ミスフォールド型タンパク質の経口摂取による毒性発揮の実験的検証

    2020.07
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Exploratory), Principal investigator

  • 生命金属動態を制御するシャペロン分子ネットワークの解明

    2019.06
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research on Innovative Areas, Principal investigator

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Courses Taught 【 Display / hide 】

  • SEMINAR IN CHEMISTRY

    2024

  • MOLECULAR BIOLOGY (BIOLOGICAL CHEMISTRY 3)

    2024

  • LABORATORY IN SCIENCE

    2024

  • LABORATORIES IN CHEMISTRY 1

    2024

  • INDEPENDENT STUDY ON FUNDAMENTAL SCIENCE AND TECHNOLOGY

    2024

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Memberships in Academic Societies 【 Display / hide 】

  • The Society of Biological Inorganic Chemistry, 

    2013.03
    -
    Present

  • 日本蛋白質科学会, 

    2010.03
    -
    Present

  • The Society for Neuroscience, 

    2009.03
    -
    Present

  • 日本神経科学学会, 

    2008.04
    -
    Present

  • 日本生物物理学会, 

    1998.03
    -
    Present

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Committee Experiences 【 Display / hide 】

  • 2014.04
    -
    Present

    アーカイブ委員, 日本蛋白質科学会

  • 2013.07
    -
    Present

    専門調査員, 文部科学省科学技術政策研究所　科学技術動向研究センター

  • 2013.01
    -
    Present

    分野別専門委員, 日本生物物理学会

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