Elucidating the RNA pathomechanism in FUS-FALS iPS induced motor neurons

• Project/Area Number: 25293199
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: Aoki Masashi 東北大学, 医学(系)研究科(研究院), 教授 (70302148)
• Co-Investigator(Kenkyū-buntansha): Kato MASAAKI 東北大学, 病院, 助教 (50622479) ; Naoki SUZUKI 東北大学, 病院, 助教 (70451599) ; Hitoshi WARITA 東北大学, 大学院医学系研究科, 助教 (30400245)
• Co-Investigator(Renkei-kenkyūsha): OKANO Hideyuki 慶應義塾大学, 医学部, 教授 (60160694)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 筋萎縮性側索硬化症 / iPS細胞 / ALS / ＡＬＳ / 神経変性疾患 / 運動ニューロン / 神経変性 / RNA

Outline of Final Research Achievements

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in the selective death of motor neurons. ALS symptoms are associated with muscle weakness and paralysis and approximately 80% of ALS patients die within 5 years after the onset of these symptoms. We generated induced pluripotent stem cells (iPSC) from familial ALS (FALS) patients with a missense mutation in the fused-in sarcoma (FUS) gene carrying the heterozygous FUS H517D mutation These cell-derived motor neurons mimicked several neurodegenerative phenotypes including mis-localization of FUS into cytosolic and stress granules under stress conditions, and cellular vulnerability (Ichiyanagi et al. Stem Cell Reports 2016).

Research Products

• [Journal Article] Establishment of in vitro FUS-associated familial amyotrophic lateral sclerosis model using human induced pluripotent stem cells. (2016)
  • Author(s): Naoki Ichiyanagi, Koki Fujimori, Masato Yano, Chikako Ishihara-Fujisaki, Takefumi Sone, Tetsuya Akiyama, Yohei Okada, Wado Akamatsu, Takuya Matsumoto, Mitsuru Ishikawa, Yoshinori Nishimoto, Yasuharu Ishihara, Tetsushi Sakuma, Takashi Yamamoto, Hitomi Tsuiji, Naoki Suzuki, Hitoshi Warita, Masashi Aoki, Hideyuki Okano
  • Journal Title: Stem Cell Reports Volume: 6 Issue: 4 Pages: 496-510
  • DOI: 10.1016/j.stemcr.2016.02.011
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genotype-phenotype relationships in familial ALS with FUS/TLS mutations in Japan (2016)
  • Author(s): Akiyama T, Warita H, Kato M, Nishiyama A, Izumi R, Ikeda C, Kamada M, Suzuki N, Aoki M
  • Journal Title: Muscle Nerve Volume: Jan 28 Issue: 3 Pages: 398-404
  • DOI: 10.1002/mus.25061
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A mutation in hnRNPA1 causes isolated inclusion body myopathy in two families with multisystem proteinopathy (2015)
  • Author(s): Izumi R, Warita H, Niihori T, Takahashi T, Tateyama M, Suzuki N, Nishiyama A, Shirota M, Funayama R, Nakayama K, Mitsuhashi S, Nishino I, Aoki Y, Aoki M.
  • Journal Title: Neurology Genetics Volume: NA
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 筋萎縮性側索硬化症の最新のトピックス FUS/TLS遺伝子異常に伴うALS (2013)
  • Author(s): 青木正志
  • Journal Title: Modern Physician Volume: 33(5) Pages: 668-673
• [Presentation] FUS変異によるALS臨床病理と病態 (2013)
  • Author(s): 青木正志
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 筋萎縮性側索硬化症モデルラット微小血管の壁細胞を標的とした運動ニューロン保護 (2013)
  • Author(s): 割田 仁，水野秀紀，加藤昌昭，鈴木直輝，青木正志
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
• [Presentation] 東北大学における家族性ALS遺伝子検査の検討 (2013)
  • Author(s): 加藤昌昭，割田 仁，井泉瑠美子，島倉奈緒子，安藤里紗，鈴木直輝，青木正志
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
• [Remarks] 東北大学神経内科
  • URL: http://www.neurol.med.tohoku.ac.jp/index.html
• [Remarks] 東北大学神経内科
  • URL: http://www.neurol.med.tohoku.ac.jp/index.html