iPSC-based disease modeling of sporadic Parkinson's disease

• Project/Area Number: 16K09677
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: Akamatsu Wado 順天堂大学, 医学(系)研究科(研究院), 特任教授 (60338184)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: iPS細胞 / パーキンソン病 / 疾患モデル / 神経幹細胞

Outline of Final Research Achievements

We have established more than 100 iPS cell lines from sporadic cases of Parkinson's disease patients at Juntendo University during the study period. The established sporadic patient-derived iPS cells were sequentially induced to differentiate into neurons, and multiple phenotypes were analyzed in each case, and the results were made into a database. Sporadic patients have a diversity of cellular phenotypes as well as clinical findings. The iPSCs and database established in this research have become important research resources that can be used in various projects in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究では100症例以上の孤発性パーキンソン病の検体を解析し、これまで実現不可能であったiPS細胞を用いた孤発性疾患の解析システムを構築した。今後はこれらの結果を指標として、個々の孤発性患者が細胞内のどの分子機構に異常を来しているかを明らかにし、新たな病態分類を確立し最適な治療法の開発の基礎となることが期待される。

Research Products

• [Journal Article] Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression (2019)
  • Author(s): Nishihara Koji、Shiga Takahiro、Nakamura Eri、Akiyama Tomohiko、Sasaki Takashi、Suzuki Sadafumi、Ko Minoru S.H.、Tada Norihiro、Okano Hideyuki、Akamatsu Wado
  • Journal Title: Stem Cell Reports Volume: 12 Issue: 2 Pages: 305-318
  • DOI: 10.1016/j.stemcr.2018.12.018
  • Peer Reviewed / Open Access
• [Journal Article] Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson's Disease. (2018)
  • Author(s): Ueno SI, Saiki S, Fujimaki M, Takeshige-Amano H, Hatano T, Oyama G, Ishikawa KI, Yamguchi A, Nojiri S, Akamatsu W, Hattori N.
  • Journal Title: Cells Volume: 8 Issue: 1 Pages: 14-14
  • DOI: 10.3390/cells8010014
  • Peer Reviewed / Open Access
• [Journal Article] Soluble epoxide hydrolase plays a key role in the pathogenesis of Parkinson’s disease (2018)
  • Author(s): Ren Qian、Ma Min、Yang Jun、Nonaka Risa、Yamaguchi Akihiro、Ishikawa Kei-ichi、Kobayashi Kenta、Murayama Shigeo、Hwang Sung Hee、Saiki Shinji、Akamatsu Wado、Hattori Nobutaka、Hammock Bruce D.、Hashimoto Kenji
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 115 Issue: 25
  • DOI: 10.1073/pnas.1802179115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Rostrocaudal Areal Patterning of Human PSC-Derived Cortical Neurons by FGF8 Signaling (2018)
  • Author(s): Imaizumi Kent、Fujimori Koki、Ishii Seiji、Otomo Asako、Hosoi Yasushi、Miyajima Hiroaki、Warita Hitoshi、Aoki Masashi、Hadano Shinji、Akamatsu Wado、Okano Hideyuki
  • Journal Title: eNeuro Volume: 5 Issue: 2 Pages: 0368-17
  • DOI: 10.1523/eneuro.0368-17.2018
  • Peer Reviewed / Open Access
• [Journal Article] Down-regulation of ghrelin receptors on dopaminergic neurons in the substantia nigra contributes to Parkinson's disease-like motor dysfunction. (2018)
  • Author(s): Suda Y, Kuzumaki N, Sone T, Narita M, Tanaka K, Hamada Y, Iwasawa C, Shibasaki M, Maekawa A, Matsuo M, Akamatsu W, Hattori N, Okano H, Narita M.
  • Journal Title: Mol Brain. Volume: 11 Issue: 1 Pages: 6-6
  • DOI: 10.1186/s13041-018-0349-8
  • Peer Reviewed / Open Access
• [Journal Article] Chemical decontamination of iPS cell-derived neural cell mixtures (2018)
  • Author(s): Mao Di、Chung Xie Khim Watson、Andoh-Noda Tomoko、Qin Ying、Sato Shin-ichi、Takemoto Yasushi、Akamatsu Wado、Okano Hideyuki、Uesugi Motonari
  • Journal Title: Chem Commun (Camb). 1355 Volume: 54 Issue: 11 Pages: 1355-1358
  • DOI: 10.1039/c7cc08686e
  • Peer Reviewed
• [Journal Article] Escape from Pluripotency via Inhibition of TGF-β/BMP and Activation of Wnt Signaling Accelerates Differentiation and Aging in hPSC Progeny Cells (2017)
  • Author(s): Fujimori Koki、Matsumoto Takuya、Kisa Fumihiko、Hattori Nobutaka、Okano Hideyuki、Akamatsu Wado
  • Journal Title: Stem Cell Reports. Volume: 9 Issue: 5 Pages: 1675-1691
  • DOI: 10.1016/j.stemcr.2017.09.024
  • Peer Reviewed / Open Access
• [Journal Article] Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson’s disease (2017)
  • Author(s): Shiba-Fukushima Kahori、Ishikawa Kei-Ichi、Inoshita Tsuyoshi、Izawa Nana、Takanashi Masashi、Sato Shigeto、Onodera Osamu、Akamatsu Wado、Okano Hideyuki、Imai Yuzuru、Hattori Nobutaka
  • Journal Title: Human Molecular Genetics Volume: 26 Pages: 3172-3185
  • DOI: 10.1093/hmg/ddx201
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Generation of neural cells using iPSCs from sleep bruxism patients with 5-HT2A polymorphism (2017)
  • Author(s): Hoashi Y, Okamoto S, Abe Y, Matsumoto T, Tanaka J, Yoshida Y, Imaizumi K, Mishima K, Akamatsu W, Okano H, Baba K
  • Journal Title: Journal of Prosthodontic Research Volume: 61 Issue: 3 Pages: 242-250
  • DOI: 10.1016/j.jpor.2016.11.003
  • NAID: 130006076280
  • ISSN: 1883-1958, 1883-9207
  • Peer Reviewed
• [Journal Article] Assessment of Mitophagy in iPS Cell-Derived Neurons. (2017)
  • Author(s): Ishikawa KI, Yamaguchi A, Okano H, Akamatsu W.
  • Journal Title: Methods Mol Biol. Volume: - Pages: 1-9
  • DOI: 10.1007/7651_2017_10
  • ISBN: 9781493977499, 9781493977505
  • Peer Reviewed
• [Journal Article] Efficient induction of dopaminergic neuron differentiation from induced pluripotent stem cells reveals impaired mitophagy in PARK2 neurons. (2017)
  • Author(s): Suzuki S, Akamatsu W, Kisa F, Sone T, Ishikawa KI, Kuzumaki N, Katayama H, Miyawaki A, Hattori N, Okano H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 489 Issue: 1 Pages: 88-93
  • DOI: 10.1016/j.bbrc.2016.12.188
  • Peer Reviewed / Open Access
• [Journal Article] Changeability of the fully methylated status of the 15q11.2 region in induced pluripotent stem cells derived from a patient with Prader-Willi syndrome. (2016)
  • Author(s): Okuno H, Nakabayashi K, Abe K, Ando T, Sanosaka T, Kohyama J, Akamatsu W, Ohyama M, Takahashi T, Kosaki K, Okano H.
  • Journal Title: Congenit Anom (Kyoto) Volume: Dec 21 Issue: 4 Pages: 96-103
  • DOI: 10.1111/cga.12206
  • NAID: 130008142312
  • Peer Reviewed
• [Journal Article] Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines. (2016)
  • Author(s): Fujimori K, Tezuka T, Ishiura H, Mitsui J, Doi K, Yoshimura J, Tada H, Matsumoto T, Isoda M, Hashimoto R, Hattori N, Takahashi T, Morishita S, Tsuji S, Akamatsu W, Okano H.
  • Journal Title: Mol Brain. Volume: 9 Pages: 88-88
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] iPS細胞を用いたパーキンソン病の病態解明 (2018)
  • Author(s): 赤松和土
  • Organizer: 第53回TOKYOニューロサイエンス研究会
  • Invited
• [Presentation] iPS細胞技術を用いた神経疾患解析 (2018)
  • Author(s): 赤松和土
  • Organizer: 第28回日本サイトメトリー学会学術集会
  • Invited
• [Presentation] Patient-specific iPS cells for neural disease modeling and drug screening (2018)
  • Author(s): 赤松和土
  • Organizer: 国際シンポジウム早老症と関連疾患 2018（RECQ2018）
  • Int'l Joint Research / Invited
• [Presentation] iPS細胞を用いた神経疾患の病態解析 (2018)
  • Author(s): 赤松和土
  • Organizer: iCell Users' Meeting 2018
  • Invited
• [Presentation] Patient-specific iPS cells for neural disease modeling and drug screening (2017)
  • Author(s): 赤松和土
  • Organizer: 65th Annual Meeting of Japanese Association for Dental Research
  • Int'l Joint Research / Invited
• [Presentation] 疾患特異的iPS細胞を用いた神経疾患モデル解析の改良 (2017)
  • Author(s): 赤松和土
  • Organizer: 第16回再生医療学会
  • Place of Presentation: 仙台市
• [Presentation] iPS細胞技術を用いた神経疾患の病態解明と治療法開発 (2016)
  • Author(s): 赤松和土
  • Organizer: 第39回小児遺伝学会
  • Place of Presentation: 東京都
  • Invited
• [Presentation] iPS細胞技術を用いた神経疾患研究 (2016)
  • Author(s): 赤松和土
  • Organizer: 日本線維筋痛症学会第8回学術集会
  • Place of Presentation: 東京都
  • Invited
• [Presentation] iPS細胞技術を用いた神経疾患解析と治療法開発 (2016)
  • Author(s): 赤松和土
  • Organizer: 第58回日本小児神経学会
  • Place of Presentation: 東京都