Integrative understanding and therapeutic application of seamless degenerative processes based on Hippo pathway

• Project/Area Number: 16H02655
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Okazawa Hitoshi 東京医科歯科大学, 難治疾患研究所, 教授 (50261996)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥47,320,000 (Direct Cost: ¥36,400,000、Indirect Cost: ¥10,920,000); Fiscal Year 2018: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000); Fiscal Year 2017: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000); Fiscal Year 2016: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
• Keywords: TRIAD / Hippo pathway / ネクローシス / 神経変性 / 細胞死 / YAP / hnRNP / Hippo / ハンチントン病 / 転写 / スプライシング / 治療 / 脳神経疾患

Outline of Final Research Achievements

In this project, we intended to define the new "Hippo pathway dependent necrosis", which the PI discovered as transcriptional repression-induced atypical neuronal death (TRIAD) in 2007 (Hoshino et al, JCB 2007), as a pathological concept that can conclusively explain the seamless progression of neurodegenerative pathologies. In parallel, we intended to develop a new therapeutics strategy targeting on this new necrosis. Consequently, we have identified new molecules regulating TRIAD/Hippo-dependent necrosis, have proven the existence of TRIAD/Hippo-dependent necrosis in human and mouse neurodegenerative states, and revealed that the suppression of TRIAD/Hippo-dependent necrosis by using AAV-vector or chemicals successfully inhibited the progression of symptoms and pathologies in mouse models of multiple neurodegenerative diseases.

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患（ハンチントン病、アルツハイマー病など）には、現時点で根本治療薬（病態修飾薬）が存在しない。本研究成果は、新しいネクローシスサブタイプ（Hippo経路依存的細胞死もしくはTRIAD）の存在を示し、その分子経路を明らかにした点で、学術的に高い価値を有するのみならず、新規細胞死を標的とする新たな治療戦略が治療困難な神経変性疾患に対して有効であることを示した点で、社会的にも極めて有意義であったと考える。

Research Products

• [Int'l Joint Research] National University of Singapore(シンガポール)
• [Journal Article] Chronic cerebral hypoperfusion shifts the equilibrium of amyloid β oligomers to aggregation-prone species with higher molecular weight (2019)
  • Author(s): Bannai Taro、Mano Tatsuo、Chen Xigui、Ohtomo Gaku、Ohtomo Ryo、Tsuchida Takeyuki、Koshi-Mano Kagari、Hashimoto Tadafumi、Okazawa Hitoshi、Iwatsubo Takeshi、Tsuji Shoji、Toda Tatsushi、Iwata Atsushi
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 2827-2827
  • DOI: 10.1038/s41598-019-39494-7
  • Peer Reviewed / Open Access
• [Journal Article] Methods to Image Macroautophagy in the Brain In Vivo (2019)
  • Author(s): Chen Xigui、Kondo Kanoh、Okazawa Hitoshi
  • Journal Title: Methods in Molecular Biology Volume: 1880 Pages: 529-534
  • DOI: 10.1007/978-1-4939-8873-0_33
  • ISBN: 9781493988723, 9781493988730
  • Peer Reviewed
• [Journal Article] Drebrin-like (Dbnl) Controls Neuronal Migration via Regulating N-Cadherin Expression in the Developing Cerebral Cortex (2018)
  • Author(s): Inoue Seika、Hayashi Kanehiro、Fujita Kyota、Tagawa Kazuhiko、Okazawa Hitoshi、Kubo Ken-ichiro、Nakajima Kazunori
  • Journal Title: The Journal of Neuroscience Volume: 39 Issue: 4 Pages: 678-691
  • DOI: 10.1523/jneurosci.1634-18.2018
  • Peer Reviewed / Open Access
• [Journal Article] 総論 シナプス研究を加速する基礎臨床連携 (2018)
  • Author(s): 岡澤 均
  • Journal Title: 月刊細胞(2018年12月号） Volume: 50 Pages: 2-4
• [Journal Article] 変性疾患におけるシナプス異常の新知見 (2018)
  • Author(s): 岡澤 均、藤田 慶大
  • Journal Title: 月刊細胞(2018年12月号） Volume: 50 Pages: 25-28
• [Journal Article] The intellectual disability gene PQBP1 rescues Alzheimer’s disease pathology (2018)
  • Author(s): Tanaka Hikari、Kondo Kanoh、Chen Xigui、Homma Hidenori、Tagawa Kazuhiko、Kerever Aurelien、Aoki Shigeki、Saito Takashi、Saido Takaomi、Muramatsu Shin-ichi、Fujita Kyota、Okazawa Hitoshi
  • Journal Title: Molecular Psychiatry Volume: 23 Issue: 10 Pages: 2090-2110
  • DOI: 10.1038/s41380-018-0253-8
  • Peer Reviewed / Open Access
• [Journal Article] Suppression of the synaptic localization of a subset of proteins including APP partially ameliorates phenotypes of the Drosophila Alzheimer's disease model (2018)
  • Author(s): Furotani Koto、Kamimura Keisuke、Yajima Takaaki、Nakayama Minoru、Enomoto Rena、Tamura Takuya、Okazawa Hitoshi、Sone Masaki
  • Journal Title: PLOS ONE Volume: 13 Issue: 9 Pages: e0204048-e0204048
  • DOI: 10.1371/journal.pone.0204048
  • Peer Reviewed / Open Access
• [Journal Article] TRIAD(Transcriptional Repression-Induced Atypical Death) (2018)
  • Author(s): Takuya Tamura、Hitoshi Okazawa
  • Journal Title: Apoptosis and Beyond :The Many Ways Cells Die Volume: 2 Pages: 411-426
  • Peer Reviewed
• [Journal Article] Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology (2018)
  • Author(s): Fujita Kyota、Homma Hidenori、Kondo Kanoh、Ikuno Masashi、Yamakado Hodaka、Tagawa Kazuhiko、Murayama Shigeo、Takahashi Ryosuke、Okazawa Hitoshi
  • Journal Title: eneuro Volume: 5 Issue: 4 Pages: 0217-18
  • DOI: 10.1523/eneuro.0217-18.2018
  • Peer Reviewed / Open Access
• [Journal Article] 第3節 凝集前病態の解明に基づくアルツハイマー病の新規DMT 開発 (2018)
  • Author(s): 藤田 慶大、 岡澤 均
  • Journal Title: アルツハイマー病 ～発症メカニズムと新規診断法・創薬・治療開発～ Volume: - Pages: 157-164
• [Journal Article] Bridging Multiple Dementias (2018)
  • Author(s): Okazawa Hitoshi
  • Journal Title: ACS Chemical Neuroscience Volume: 9 Issue: 4 Pages: 636-638
  • DOI: 10.1021/acschemneuro.8b00119
  • Peer Reviewed / Open Access
• [Journal Article] Mild maternal hypothyroxinemia during pregnancy induces persistent DNA hypermethylation in the hippocampal brain-derived neurotrophic factor gene in mouse offspring (2018)
  • Author(s): Kawahori K, Hashimoto K, Yuan X, Tsujimoto K, Hanzawa N, Hamaguchi M, Kase S, Fujita K, Tagawa K, Okazawa H, Nakajima Y, Shibusawa N, Yamada M, Ogawa Y
  • Journal Title: Thyroid Volume: 28 Issue: 3 Pages: 395-406
  • DOI: 10.1089/thy.2017.0331
  • Peer Reviewed
• [Journal Article] Targeting Tyro3 ameliorates a model of PGRN-mutant FTLD-TDP via tau-mediated synaptic pathology (2018)
  • Author(s): Fujita Kyota、Chen Xigui、Homma Hidenori、Tagawa Kazuhiko、Amano Mutsuki、Saito Ayumu、Imoto Seiya、Akatsu Hiroyasu、Hashizume Yoshio、Kaibuchi Kozo、Miyano Satoru、Okazawa Hitoshi
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 433-433
  • DOI: 10.1038/s41467-018-02821-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Relationship between Neurite Density Measured with Confocal Microscopy in a Cleared Mouse Brain and Metrics Obtained from Diffusion Tensor and Diffusion Kurtosis Imaging (2018)
  • Author(s): Irie R、 Kamagata K、 Kerever A、 Ueda R、Yokosawa S、 Otake Y、Ochi H、Yoshizawa H、Hayashi A、Tagawa K、Okazawa Hitoshi、Takahashi K、Sato K、 Hori M、 Arikawa-Hirasawa E、Aoki S
  • Journal Title: Magnetic Resonance in Medical Sciences Volume: 17 Issue: 2 Pages: 138-144
  • DOI: 10.2463/mrms.mp.2017-0031
  • NAID: 130006685597
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed / Open Access
• [Journal Article] ハンチントン病 (2018)
  • Author(s): 岡澤 均、本間 秀典
  • Journal Title: Clinical Neuroscience Vol.36 No.2 Volume: 36 Pages: 213-215
• [Journal Article] 特集 遺伝性脊髄小脳失調症の病態と治療展望 HMGB1補充による脊髄小脳失調症1型に対する分子標的治療 (2017)
  • Author(s): 藤田 慶大、岡澤 均
  • Journal Title: BRAIN and NERVE Volume: 69 Issue: 8 Pages: 925-932
  • DOI: 10.11477/mf.1416200844
  • ISSN: 1344-8129, 1881-6096
  • Year and Date: 2017-08-01
• [Journal Article] Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1. (2017)
  • Author(s): Fujita K, Mao Y, Uchida S, Chen X, Shiwaku H, Tamura T, Ito H, Watase K, Homma H, Tagawa K, Sudol M, Okazawa H.
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 1864-1864
  • DOI: 10.1038/s41467-017-01790-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PQBP1, an intrinsically disordered/denatured protein at the crossroad of intellectual disability and neurodegenerative diseases (2017)
  • Author(s): Okazawa Hitoshi
  • Journal Title: Neurochemistry International Volume: 印刷中 Pages: 17-25
  • DOI: 10.1016/j.neuint.2017.06.005
  • Peer Reviewed / Open Access
• [Journal Article] Ultra-Early Phase pathologies of Alzheimer’s disease and other neurodegenerative diseases (2017)
  • Author(s): Okazawa Hitoshi
  • Journal Title: Proceedings of the Japan Academy, Series B Volume: 93 Issue: 6 Pages: 361-377
  • DOI: 10.2183/pjab.93.022
  • NAID: 130005696850
  • ISSN: 0386-2208, 1349-2896
  • Peer Reviewed / Open Access
• [Journal Article] Understanding microstructure of the brain by comparison of neurite orientation dispersion and density imaging (NODDI) with transparent mouse brain. (2017)
  • Author(s): Sato K, Kerever A, Kamagata K, Tsuruta K, Irie R, Tagawa K, Okazawa H, Arikawa-Hirasawa E, Nitta N, Aoki I, Aoki S.
  • Journal Title: Acta Radiologica Open Volume: 6 Issue: 4 Pages: 1-6
  • DOI: 10.1177/2058460117703816
  • Peer Reviewed / Open Access
• [Journal Article] 発症分子機構update 3.アミロイド凝集前の超早期病態とその抑制 (2017)
  • Author(s): 岡澤 均、藤田 慶大
  • Journal Title: 実験医学増刊 vol.35 No.12 Volume: 35 Pages: 198-203
• [Journal Article] A novel form of necrosis, TRIAD, occurs in human Huntington's disease (2017)
  • Author(s): Yamanishi, E., Hasegawa, K., Fujita, K., Ichinose, S., Yagishita, S., Murata, M., Tagawa, K., Akashi, T., Eishi, Y., Okazawa, H.
  • Journal Title: Acta Neuropathologica Communications Volume: 5 Issue: 1
  • DOI: 10.1186/s40478-017-0420-1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The hnRNP-Htt axis regulates necrotic cell death induced by transcriptional repression through impaired RNA splicing (2016)
  • Author(s): Y. Mao, T. Tamura, Y. Yuki, D. Abe, Y. Tamada, S. Imoto, H. Tanaka, H. Homma, K. Tagawa, S. Miyano and H. Okazawa
  • Journal Title: Cell Death and Disease Volume: 7 Issue: 4 Pages: e2207-e2207
  • DOI: 10.1038/cddis.2016.101
  • Peer Reviewed / Open Access
• [Journal Article] Allosteric modulation of the binding affinity between PQBP1 and the spliceosomal protein U5-15kD (2016)
  • Author(s): Mizuguchi, M., Obita, T., Kajiyama, A., Kozakai, Y., Nakai, T., Nabeshima, Y., Okazawa, H.
  • Journal Title: FEBS Letters Volume: 590 Issue: 14 Pages: 2221-31
  • DOI: 10.1002/1873-3468.12256
  • Peer Reviewed
• [Journal Article] RpA1 ameliorates symptoms of mutant Ataxin-1 knock-in mice and enhances DNA damage repair (2016)
  • Author(s): Taniguchi, JB., Kondo, K., Fujita, K., Chen, X., Homma, H., Sudo, T., Mao, Y., Watase, K., Tanaka, T., Tagawa, K., Tamura, T., Muramatsu, SI., Okazawa, H.
  • Journal Title: Human Molecular Genetics Volume: 25 Pages: 4432-4447
  • DOI: 10.1093/hmg/ddw272
  • Peer Reviewed
• [Journal Article] HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer's disease (2016)
  • Author(s): Fujita, K., Motoki, K., Tagawa, K., Chen, X., Hama, H., Nakajima, K., Homma, H., Tamura, T., Watanabe, H., Katsuno, M., Matsumi, C., Kajikawa, M., Saito, T., Saido, T., Sobue, G., Miyawaki, A., Okazawa, H.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 31895-31895
  • DOI: 10.1038/srep31895
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Targeting TEAD/YAP-transcription-dependent necrosis, TRIAD, ameliorates Huntington’s disease pathology (2016)
  • Author(s): Mao, Y., Chen, X., Xu, M.,Fujita, K., Sasabe, K.,Homma, H., Murata, M., Tagawa, K., Tamura, T., Kaye, J., Finkbeiner, S., Blandino, G., Sudol, M., Okazawa, H.
  • Journal Title: Human Molecular Genetics Volume: 25 Pages: 4749-4770
  • DOI: 10.1093/hmg/ddw303
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of hepta-histidine as a candidate drug for Huntington’s disease by in silico-in vitro-in vivo-integrated screens of chemical libraries (2016)
  • Author(s): Imamura, T., Fujita, K., Tagawa, K., Ikura, T., Chen, X., Homma, H., Tamura, T., Mao, Y., Taniguchi, JB., Motoki, K., Nakabayashi, M., Ito, N., Yamada, K., Tomii, K., Okano, H., Kaye, J., Finkbeiner, S., Okazawa, H.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1
  • DOI: 10.1038/srep33861
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 「特集 「認知症・神経変性疾患の克服への挑戦」によせて」 (2016)
  • Author(s): 岡澤 均
  • Journal Title: 生体の科学 Volume: 67 Pages: 280-280
• [Journal Article] 「1990年以後の神経栄養因子臨床試験からの知見と教訓」 (2016)
  • Author(s): 岡澤 均、本木 和美
  • Journal Title: 生体の科学 Volume: 67 Pages: 291-295
• [Journal Article] 「変性疾患の共通分子病態」 (2016)
  • Author(s): 藤田 慶大、岡澤 均
  • Journal Title: 生体の科学 Volume: 67 Pages: 309-313
• [Journal Article] 「アルツハイマー病の“超早期”治療を可能にする分子メカニズムと治療薬開発」 (2016)
  • Author(s): 岡澤 均
  • Journal Title: 月刊ファームステージ 2016.12月号 Volume: 16 Pages: 39-45
  • NAID: 40021030556
• [Presentation] Developmental YAPdeltaC determines adult pathology of spinocerebellar ataxia type 1 (2018)
  • Author(s): Hitoshi Okazawa
  • Organizer: the 75th FUJIHARA Seminar
  • Int'l Joint Research / Invited
• [Presentation] HMGB1が仲介するアルツハイマー病の超早期病態 (2018)
  • Author(s): 岡澤 均
  • Organizer: 岡山大学大学院医歯薬学総合研究科特別講義
  • Invited
• [Presentation] 慢性脳低灌流がアルツハイマー病における脳内アミロイドβ蓄積を増加させる機序の解明 (2018)
  • Author(s): 坂内太郎、間野達雄、陳西貴、大友亮、大友岳、橋本唯史、岡澤均、岩坪威、戸田達史、岩田淳
  • Organizer: 第37回日本認知症学会学術集会
• [Presentation] アルツハイマー病と前頭側頭葉変性症に共通する異常タウリン酸化とシナプス障害 (2018)
  • Author(s): 藤田慶大、陳西貴、本間秀典、田川一彦、岡澤均
  • Organizer: 第37回日本認知症学会学術集会
• [Presentation] 認知症の超早期病態と新たな治療戦略 (2018)
  • Author(s): 岡澤 均
  • Organizer: 市民公開講演会
  • Invited
• [Presentation] Symptomatic and Disease Modifying Treatments for Chorea and Huntington’s Disease (2018)
  • Author(s): Hitoshi Okazawa
  • Organizer: MDS2018 International Congress
  • Int'l Joint Research / Invited
• [Presentation] Comprehensive proteome analysis reveals ultra-early phase pathologies of neurodegenerative diseases (2018)
  • Author(s): Hitoshi Okazawa
  • Organizer: ICN 2018 Tokyo
  • Int'l Joint Research / Invited
• [Presentation] Novel Hippo pathway-dependent necrosis, TRIAD and Huntington’s disease (2018)
  • Author(s): Hitoshi Okazawa
  • Organizer: ICN 2018 Tokyo
  • Int'l Joint Research / Invited
• [Presentation] ＨＭＧＢ１を介した認知症の超早期病態と治療開発 (2018)
  • Author(s): 岡澤 均
  • Organizer: 第40回日本生物学的精神医学会・第61 回日本神経化学会大会
  • Invited
• [Presentation] Reelin-DBNL signaling regulates neuronal migration via N-cadherin/α -N-catenin complex in the intermediate zone and multipolar cell accumulate zone of the developing mouse cerebral neocortex (2018)
  • Author(s): Seika Inoue, Kanehiro Hayashi, Kyota Fujita, Kazuhiko Tagawa, Hitoshi Okazawa Ken-ichiro Kubo,Kazunori Nakajima,
  • Organizer: 第40回日本生物学的精神医学会・第61 回日本神経化学会大会
• [Presentation] The hnRNP-Htt axis regulates necrotic cell death induced by transcriptional repression through impaired RNA splicing (2018)
  • Author(s): Hikari Tanaka, Ying Mao, Takuya Tamura, Yoshie Yuki, Daisu Abe, Hidenori Homma,Kazuhiko Tagawa, Hitoshi Okazawa
  • Organizer: 第41回日本神経科学大会
• [Presentation] Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1 (2018)
  • Author(s): Kazuhiko Tagawa, Kyota Fujita Ying Mao, Shigenori Uchida, Xigui Chen, Kei Watase, Hidenori Homma, Marius Sudol, Hitoshi Okazawa
  • Organizer: 第41回日本神経科学大会
• [Presentation] ハンチントン病における新規ネクローシスTRIADの分子病態 (2018)
  • Author(s): 藤田 慶大、Ying Mao、陳 西貴、山西 恵美子、本間 秀典、田川 一彦、岡澤 均
  • Organizer: 第41回日本神経科学大会
• [Presentation] In vivo imaging of intracellular organelle in neurons of Alzheimer's disease and other neurodegenerative disease model (2018)
  • Author(s): Kanoh Kondo, Xigui Chen, Kazumi Motoki, Hidenori Homma, Hitoshi Okazawa
  • Organizer: 第41回日本神経科学大会
• [Presentation] Comprehensive analyses reveal new concepts of neurodegeneration in time axis (2018)
  • Author(s): Hitoshi Okazawa
  • Organizer: JNS-JSN Joint Symposium
  • Int'l Joint Research / Invited
• [Presentation] 神経変性疾患の超早期病態の解明に向けて (2018)
  • Author(s): 岡澤 均
  • Organizer: 第23回山梨神経先端セミナー
  • Invited
• [Presentation] アルツハイマー病等の認知症に対する新規治療法開発 (2018)
  • Author(s): 岡澤 均
  • Organizer: 技術情報協会 認知症セミナー（認知症の早期診断と進行抑制薬開発へのポイント）
  • Invited
• [Presentation] 網羅的解析ビッグデータを基盤とする認知症・変性疾患の理解と応用 (2018)
  • Author(s): 岡澤 均
  • Organizer: OYCバイオシンポジウム2018
  • Invited
• [Presentation] Developmental YAPdeltaC determines adult pathology in a mouse model of spinocerebellarataxia type 1 (2018)
  • Author(s): 藤田 慶大、毛 瀅、内田 成則、陳 西貴、塩飽 裕紀、田村 拓也、伊藤 日加瑠、本間 秀典、田川 一彦、岡澤 均
  • Organizer: 第59回日本神経学会学術大会
• [Presentation] 網羅的分子ネットワーク解析が紐解く新たな神経変性病態と治療応用 (2018)
  • Author(s): 岡澤 均
  • Organizer: 第55回日本臨床分子医学会学術集会
  • Invited
• [Presentation] New Molecularly Targeted Therapeutics Deduced from Unbiased Approaches (2018)
  • Author(s): Hitoshi Okazawa
  • Organizer: 21st US-Japan Cellular and Gene Therapy Conference.
  • Int'l Joint Research / Invited
• [Presentation] 脊髄小脳変性症の遺伝子治療 (2018)
  • Author(s): 岡澤 均
  • Organizer: 第１回毛細血管拡張性運動失調症（AT）研究会
  • Invited
• [Presentation] HMGB1 and Neurodegeneration (2017)
  • Author(s): Hitoshi Okazawa
  • Organizer: 8th International DAMPs and Alarmins Symposium (iDEAs)
  • Int'l Joint Research / Invited
• [Presentation] Gene Therapy Against Spinocerebellar Ataxia (2017)
  • Author(s): Hitoshi Okazawa
  • Organizer: XXIII World Congress of Neurology (WCN2017）
  • Int'l Joint Research / Invited
• [Presentation] Common pathologies across multiple neurodegenerative diseases revealed from unbiased approaches (2017)
  • Author(s): Hitoshi Okazawa
  • Organizer: MyNEURO 2017
  • Int'l Joint Research / Invited
• [Presentation] Impaired DNA Damage Repair in SCA1 and Other CAG Repeat Diseases (2017)
  • Author(s): Hitoshi Okazawa
  • Organizer: Gordon Research Conference
  • Int'l Joint Research / Invited
• [Presentation] Targeting TEAD/YAP-transcription-dependent necrosis, TRIAD, ameliorates Huntington's disease pathology (2017)
  • Author(s): Mao Ying, Xigui Chen, Xu Min, Kyota Fujita, Kazumi Motoki, Toshikazu Sasabe, Hidenori Homma, Miho Murata, Kazuhiko Tagawa, Takuya Tamura, Kaye Julia, Steven Finkbeiner, Giovanni Blandino, Marius Sudol, Kanoh Kondo, Hitoshi Okazawa.
  • Organizer: 第58回日本神経学会学術大会・第23回世界神経学会議
• [Presentation] HMGB1 TRIGGERS NEURITE DEGENERATION VIA TLR4-MARCKS, AND IS A POTENTIAL THERAPEUTIC TARGET FOR ALZHEIMER’S DISEASE. (2017)
  • Author(s): Kyota Fujita, Kazumi Motoki, Kazuhiko Tagawa, Xigui Chen, Hiroshi Hama, Kazuyuki Nakajima, Hidenori Homma, Takuya Tamura, Atsushi Miyawaki, Hitoshi Okazawa
  • Organizer: World Congress of Neurology (WCN 2017)
• [Presentation] RPA1 AMELIORATES SYMPTOMS OF MUTANT ATAXIN-1 KNOCK-IN MICE AND ENHANCE DNA DAMAGE REPAIR (2017)
  • Author(s): Juliana Bosso Taniguchi, Kanoh Kondo, Kyota Fujita, Xigui Chen, Hidenori Homma , Ying Mao , Kazuhiko Tagawa , Hitoshi Okazawa
  • Organizer: 第58回日本神経学会学術大会・第23回世界神経学会議
• [Presentation] Hippoシグナル依存的な新規ネクローシス“TRIAD”と神経変性 (2017)
  • Author(s): 岡澤 均
  • Organizer: 第26回日本Cell Death学会学術集会
  • Invited
• [Presentation] Targeting TEAD/YAP-transcription-dependent necrosis, TRIAD, ameliorates Huntington's disease pathology (2017)
  • Author(s): Mao Ying, Xigui Chen, Xu Min, Kyota Fujita, Kazumi Motoki, Toshikazu Sasabe, Hidenori Homma, Miho Murata, Kazuhiko Tagawa, Takuya Tamura, Kaye Julia, Steven Finkbeiner, Giovanni Blandino, Marius Sudol, Kanoh Kondo, Hitoshi Okazawa
  • Organizer: 第40回日本神経科学大会
• [Presentation] Effect of specific inhibition of synaptic delivery of APP by loss-of-function of yata on the Drosophila Alzheimer's disease model (2017)
  • Author(s): Masaki Sone, Koto Furotani, Taka-aki Yajima, Takuya Tamura, Hitoshi Okazawa
  • Organizer: 第40回日本神経科学大会
• [Presentation] RpA1 ameliorates symptoms of mutant ataxin-1 knock-in mice and enhances DNA damage repair (2017)
  • Author(s): Juliana Bosso Taniguchi, Kanoh Kondo, Kyota Fujita, Chen Xigui, Hidenori Homma, Takeaki Sudo,Ying Mao, Kei Watase, Toshihiro Tanaka, Kazuhiko Tagawa, Takuya Tamura, Shin-Ichi Muramatsu, Hitoshi Okazawa
  • Organizer: 第40回日本神経科学大会
• [Presentation] HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer's disease (2017)
  • Author(s): Kyota Fujita, Kazumi Motoki, Kazuhiko Tagawa, Xigui Chen, Hiroshi Hama, Kazuyuki Nakajima, Hidenori Homma, Takuya Tamura, Masahisa Katsuno, Takashi Saito, Takaomi Saido, Gen Sobue, Atsushi Miyawaki, Hitoshi Okazawa
  • Organizer: 第40回日本神経科学大会
• [Presentation] Common pathologies across multiple neurodegenerative diseases revealed from unbiased approaches (2017)
  • Author(s): 岡澤 均
  • Organizer: 第12回研究所ネットワーク国際シンポジウム
  • Invited
• [Presentation] Conceptual merge between aging and neurodegeneration (2017)
  • Author(s): Hitoshi Okazawa
  • Organizer: 第16回駿河台シンポジウム/第8回難治疾患共同研究拠点シンポジウム
  • Invited
• [Presentation] HMGB1によるミトコンドリア修復機能および遺伝子治療への展開 (2017)
  • Author(s): 岡澤 均
  • Organizer: AMEDミトコンドリアシンポジウム
  • Invited
• [Presentation] ポリグルタミン病の共通病態を基盤とする分子標的治療の開発 (2017)
  • Author(s): 岡澤 均
  • Organizer: 第32回日本大脳基底核研究会（JBAGS2017）
  • Invited
• [Presentation] 認知症治療の最前線：超早期病態へのアプローチ (2017)
  • Author(s): 岡澤 均
  • Organizer: 第18回市民公開講座
  • Invited
• [Presentation] Systematic Analysis of Fly Models Elucidates Sleep disturbance in Huntington’s Disease” (2016)
  • Author(s): Takuya Tamura, Risa Shiraishi, Masaki Sone, Hitoshi Okazawa.
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸国際展示場（兵庫県神戸市）
• [Presentation] “Analysis of molecular mechanism and development of therapeutic methods in spinocerebellar ataxia type 1 (SCA1)” (2016)
  • Author(s): Hikaru Ito, Kyota Fujita, Xigui Chen, Hitoshi Okazawa.
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸国際展示場（兵庫県神戸市）
• [Presentation] “Fasting activates macroautophagy in neurons of AD mice but is insufficient to degrade amyloid-beta” (2016)
  • Author(s): Xigui Chen, Kanoh Kondo, Kazumi Motoki, Hidenori Homma, Hitoshi Okazawa.
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸国際展示場（兵庫県神戸市）
• [Presentation] 「SCAに対する新規遺伝子治療法の開発」 (2016)
  • Author(s): 岡澤 均
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸国際展示場（兵庫県神戸市）
  • Invited
• [Presentation] 「網羅的リン酸化プロテオーム解析による早期AD病態の解明」 (2016)
  • Author(s): 田川 一彦
  • Organizer: 第46回日本神経精神薬理学会年会
  • Place of Presentation: COEX（韓国ソウル）
  • Int'l Joint Research / Invited
• [Presentation] “Gene therapy to conquer spinocerebellar ataxia” (2016)
  • Author(s): Hitoshi Okazawa
  • Organizer: 第22回日本遺伝子細胞治療学会 (JSGCT2016)
  • Place of Presentation: 虎の門ヒルズフォーラム（東京）
  • Int'l Joint Research / Invited
• [Presentation] “Fasting activates macroautophagy in neurons of Alzheimer’s disease mice but is insufficient to degrade amyloid-beta” (2016)
  • Author(s): Xigui Chen, Kanoh Kondo, Kazumi Motoki, Hidenori Homma, Hitoshi Okazawa.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Int'l Joint Research
• [Presentation] “Interaction of spliceosomal proteins PQBP1, U5-15kD, and WBP11” (2016)
  • Author(s): Mineyuki Mizuguchi, Yuko Nabeshima, Takayuki Obita, Hitoshi Okazawa.
  • Organizer: The XXVIIth International Conference on Magnetic Resonance in Biological Systems.
  • Place of Presentation: International Conference Center Kyoto （京都府京都市）
  • Int'l Joint Research
• [Presentation] “Effect of inhibition of synaptic delivery of APP by loss-of-function of yata for the Drosophila Alzheimer's disease model” (2016)
  • Author(s): Koto Furotani, Takaaki Yajima, Motoharu Toyokawa, Minoru Nakayama, Takuya Tamura, Hitoshi Okazawa, Masaki Sone.
  • Organizer: 第12回日本ショウジョウバエ研究会
  • Place of Presentation: 立教大学（東京）
• [Presentation] “Effect of inhibition of synaptic delivery of APP by the loss-of-function mutation of yata for the Drosophila Alzheimer's disease model” (2016)
  • Author(s): Koto Furotani, Takaaki Yajima, Motoharu Toyokawa, Minoru Nakayama, Takuya Tamura, Hitoshi Okazawa, Masaki Sone.
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Int'l Joint Research
• [Presentation] 「変性型認知症の分子メカニズムの共通性と特異性」 (2016)
  • Author(s): 岡澤 均
  • Organizer: 第35回日本認知症学会学術集会
  • Place of Presentation: 東京国際フォーラム（東京）
  • Invited
• [Book] 神経疾患最新の治療2018-2020 (2018)
  • Author(s): 水澤 英洋、山口 修平、園生 雅弘 編
  • Total Pages: 370
  • Publisher: 南江堂
  • ISBN: 9784524252190
• [Book] 運動失調のみかた,考えかた (2017)
  • Author(s): 宇川 義一 編
  • Total Pages: 358
  • Publisher: 中外医学社
  • ISBN: 9784498228900
• [Remarks] 「アルツハイマー病の新規病態と遺伝子治療法の発見」新規の超早期病態分子を標的にした治療法開発にむけて
  • URL: http://www.tmd.ac.jp/press-release/20181005_1/index.html
• [Remarks] 東京医科歯科大学 神経病理学
  • URL: http://www.tmd.ac.jp/npat/
• [Remarks] 東京医科歯科大学 脳統合機能研究センター
  • URL: http://www.tmd.ac.jp/cbir/
• [Patent(Industrial Property Rights)] ＭＡＲＣＫＳのリン酸化を指標にしたＡＤ（アルツハイマー病）、ＦＴＬＤ（前頭側頭葉変性症）、ＡＬＳ（筋萎縮性側索硬化症）、ＰＤ（パーキンソン病）およびＤＬＢ（レビー小体型認知症）の検出 (2019)
  • Inventor(s): 岡澤 均
  • Industrial Property Rights Holder: 東京医科歯科大学、デンカ生研株式会社
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
  • Overseas
• [Patent(Industrial Property Rights)] 前頭側頭葉変性症治療剤、前頭側頭葉変性症治療剤のスクリーニング方法、及び前頭側頭葉変性症の治療方法 (2019)
  • Inventor(s): 岡澤 均
  • Industrial Property Rights Holder: 東京医科歯科大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
  • Overseas
• [Patent(Industrial Property Rights)] ｐＳｅｒ４６－ＭＡＲＣＫＳに特異的に結合するモノクローナル抗体の配列 (2018)
  • Inventor(s): 岡澤 均
  • Industrial Property Rights Holder: 東京医科歯科大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-212340
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] ヒトＨＭＧＢ１に特異的に結合するヒトモノクローナル抗体、及びそれを含有するアルツハイマー病を治療又は予防するための医薬組成物 (2018)
  • Inventor(s): 岡澤 均
  • Industrial Property Rights Holder: 東京医科歯科大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-176802
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] ＭＡＲＣＫＳのリン酸化を指標にしたＡＤ（アルツハイマー病）、ＦＴＬＤ（前頭側頭葉変性症）、ＡＬＳ（筋萎縮性側索硬化症）、ＰＤ（パーキンソン病）およびＤＬＢ（レビー小体型認知症）の検出 (2018)
  • Inventor(s): 岡澤 均
  • Industrial Property Rights Holder: 東京医科歯科大学、デンカ生研株式会社
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-138785
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] MARKSのリン酸化を指標にしたAD（アルツハイマー病）、FTLD（前頭側頭葉変性症）およびALS（筋萎縮性側索硬化症）の検出 (2018)
  • Inventor(s): 岡澤 均、デンカ生研
  • Industrial Property Rights Holder: 岡澤 均、デンカ生研
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-043641
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] Gas6-Tyro3シグナルを標的とする神経変性の抑制方法 (2018)
  • Inventor(s): 岡澤 均
  • Industrial Property Rights Holder: 岡澤 均
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
  • Overseas
• [Patent(Industrial Property Rights)] ＨＭＧＢ１抗体によるアルツハイマー病治療 (2017)
  • Inventor(s): 岡澤 均
  • Industrial Property Rights Holder: 岡澤 均
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
  • Overseas
• [Patent(Industrial Property Rights)] HMGB1に対する抗体、及びそれを含有するアルツハイマー病を治療又は予防するための組成物 (2016)
  • Inventor(s): 岡澤 均
  • Industrial Property Rights Holder: 国立大学法人東京医科歯科大学 株式会社医学生物学研究所
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-08-09
  • Overseas
• [Patent(Industrial Property Rights)] 神経変性疾患タンパク質の異常凝集を伴って発症する神経疾患に対する予防又は治療剤、及び上記予防又は治療剤のスクリーニング方法 (2016)
  • Inventor(s): 岡澤 均
  • Industrial Property Rights Holder: 国立大学法人東京医科歯科大学 株式会社ペプチド研究所
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-177528
  • Filing Date: 2016-09-12
• [Patent(Industrial Property Rights)] 神経幹細胞の増殖の促進に用いられる製剤、神経幹細胞の減少に関連する疾患の予防又は治療に用いられる製剤（以下略） (2016)
  • Inventor(s): 岡澤 均
  • Industrial Property Rights Holder: 国立大学法人東京医科歯科大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-531427
  • Filing Date: 2016-12-27