Investigating the pathomechanism underlying idiopathic Parkinson's disease using patient-derived iPS cells

• Project/Area Number: 26860666
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Kyoto University
• Principal Investigator: Yamakado Hodaka 京都大学, 医学(系)研究科(研究院), 助教 (10378771)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: パーキンソン病

Outline of Final Research Achievements

Genomic sequencing was performed to identify GBA-related Parkinson's disease patients, and five clones of iPS cells from 6 patients were generated by plasmid methods. Genome editing by CRISPR/cas9 was employed to edit GBA gene (L444), but its efficiency was about 10%, and it was lower than expected, even in HEK 293 cells. To overcome the disadvantages from heterogeneity of genetic background in iPS research, we are analyzing the corin-sorted dopaminergic precursor cells, as well as increasing the number of target clones.

Research Products

• [Journal Article] Viable neuronopathic Gaucher disease model in medaka (Oryzias latipes) displays axonal accumulation of alpha-synuclein (2015)
  • Author(s): Norihito Uemura, Masato Koike, Satoshi Ansai, Masato Kinoshita, Tomoko Ishikawa-Fujiwara, Hideaki Matsui, Kiyoshi Naruse, Naoaki Sakamoto, Yasuo Uchiyama, Takeshi Todo, Shunichi Takeda, Hodaka Yamakado, Ryosuke Takahashi
  • Journal Title: PLoS Genetics Volume: 11 Issue: 4 Pages: 1-14
  • DOI: 10.1371/journal.pgen.1005065
  • Peer Reviewed / Open Access
• [Journal Article] Advance in PD research explored a new field on ubiquitin biology. (2014)
  • Author(s): Yamakado H.
  • Journal Title: Movement Disordes Volume: 29 Issue: 10 Pages: 1243-1243
  • DOI: 10.1002/mds.25977
  • Peer Reviewed / Open Access
• [Journal Article] Two cases of acute onset of focal cortical reflex myoclonus following acute aseptic meningoencephalitis with positive anti-glutamate receptor autoantibody. (2014)
  • Author(s): Tojima M, Hitomi T, Jingami N, Tanioka K, Yamakado H, Matsumoto R, Takahashi Y, Ikeda A, Takahashi R.
  • Journal Title: Rinsho Shinkeigaku Volume: 54 Pages: 543-549
  • NAID: 130004678995
  • Peer Reviewed / Open Access
• [Journal Article] Exploring the Pathogenetic Mechanisms underlying Parkinson's Disease in Medaka Fish. (2014)
  • Author(s): Matsui H, Uemura N, Yamakado H, Takeda S, Takahashi R
  • Journal Title: J Parkinsons Dis Volume: 4 Issue: 2 Pages: 301-310
  • DOI: 10.3233/jpd-130289
  • Peer Reviewed / Open Access
• [Presentation] Two cases of Parkinson’s disease with GBA heterozygous mutation（c.1447_1466delinsTG） (2015)
  • Author(s): 陣上直人、山下博史、山門穂高、他
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-14
• [Presentation] GBA1ノックアウトメダカの病態におけるGBA2の関与 (2015)
  • Author(s): 中西 悦郎 、上村 紀仁、秋山 央子 、木下 政人、山門 穂高、武田 俊一、平林 義雄、高橋 良輔
  • Organizer: Neuroscience 2015
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] Therapeutic approach to Parkinson’s disease by modifying α-synuclein transcription (2014)
  • Author(s): Hodaka Yamakado, Takeshi Asano, Ryosuke Takahashi
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-24