Furukawa, Yoshiaki

写真a

Affiliation

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

Position

Professor

Related Websites

External Links

 

Research Areas 【 Display / hide

  • Functional biochemistry

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

  • Oxidative misfolding of Cu/Zn-superoxide dismutase triggered by non-canonical intramolecular disulfide formation

    Anzai I., Tokuda E., Handa S., Misawa H., Akiyama S., Furukawa Y.

    Free Radical Biology and Medicine (Free Radical Biology and Medicine)  147   187 - 199 2020.02

    ISSN  08915849

     View Summary

    © 2019 Elsevier Inc. Misfolded Cu/Zn-superoxide dismutase (SOD1) is a pathological species in a subset of amyotrophic lateral sclerosis (ALS). Oxidative stress is known to increase in affected spinal cords of ALS and is thus considered to cause damages on SOD1 leading to the misfolding and aggregation. Despite this, it still remains elusive what triggers misfolding of SOD1 under oxidizing environment. Here, we show that a thiol group of Cys111 in SOD1 is oxidized to a sulfenic acid with hydrogen peroxide and reveal that further dissociation of the bound metal ions from the oxidized SOD1 allows another free Cys residue (Cys6) to nucleophilically attack the sulfenylated Cys111. As a result, an intra-molecular disulfide bond forms between Cys6 and Cys111. Such an abnormal SOD1 with the non-canonical disulfide bond was conformationally extended with significant cytotoxicity as well as high propensity to aggregate. Taken together, we propose a new model of SOD1 misfolding under oxidizing environment, in which formation of the non-canonical intramolecular disulfide bond plays a pivotal role.

  • Wild-type Cu/Zn-superoxide dismutase is misfolded in cerebrospinal fluid of sporadic amyotrophic lateral sclerosis

    Tokuda E., Takei Y.I., Ohara S., Fujiwara N., Hozumi I., Furukawa Y.

    Molecular Neurodegeneration (Molecular Neurodegeneration)  14 ( 1 )  2019.11

     View Summary

    © 2019 The Author(s). Background: A subset of familial forms of amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene coding Cu/Zn-superoxide dismutase (SOD1). Mutant SOD1 proteins are susceptible to misfolding and abnormally accumulated in spinal cord, which is most severely affected in ALS. It, however, remains quite controversial whether misfolding of wild-type SOD1 is involved in more prevalent sporadic ALS (sALS) cases without SOD1 mutations. Methods: Cerebrospinal fluid (CSF) from patients including sALS as well as several other neurodegenerative diseases and non-neurodegenerative diseases was examined with an immunoprecipitation assay and a sandwich ELISA using antibodies specifically recognizing misfolded SOD1. Results: We found that wild-type SOD1 was misfolded in CSF from all sALS cases examined in this study. The misfolded SOD1 was also detected in CSF from a subset of Parkinson's disease and progressive supranuclear palsy, albeit with smaller amounts than those in sALS. Furthermore, the CSF samples containing the misfolded SOD1 exhibited significant toxicity toward motor neuron-like NSC-34 cells, which was ameliorated by removal of the misfolded wild-type SOD1 with immunoprecipitation. Conclusions: Taken together, we propose that misfolding of wild-type SOD1 in CSF is a common pathological process of ALS cases regardless of SOD1 mutations.

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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 (general)

  • 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

  • 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, 古川 良明, 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, 古川 良明, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • 分子夾雑環境におけるタンパク質の金属イオン獲得メカニズム

    2018.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 古川 良明, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • 異常構造型脳タンパク質の経口摂取による神経変性疾患発症の可能性

    2017.04
    -
    2019.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 古川 良明, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • 定量的メタロプロテオミクスが明らかにする細胞内金属イオンの恒常性維持メカニズム

    2016.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 古川 良明, Grant-in-Aid for Scientific Research (B), Principal Investigator

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Courses Taught 【 Display / hide

  • TOPICS IN BIOINORGANIC CHEMISTRY

    2021

  • SEMINAR IN CHEMISTRY

    2021

  • MOLECULAR BIOLOGY (BIOLOGICAL CHEMISTRY 3)

    2021

  • LABORATORY IN SCIENCE

    2021

  • LABORATORIES IN CHEMISTRY 1

    2021

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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