- 著者
- Goto Kazuya Imamura Keiko Komatsu Kenichi Mitani Kohnosuke Aiba Kazuhiro Nakatsuji Norio Inoue Makoto Kawata Akihiro Yamashita Hirofumi Takahashi Ryosuke Inoue Haruhisa
- 出版者
- Elsevier B.V.
- 雑誌
- Molecular Therapy - Methods & Clinical Development (ISSN:23290501)
- 巻号頁・発行日
- vol.4, pp.115-125, 2017-03-17
- 被引用文献数
- 30
センダイウイルスベクターを用いてES細胞/iPS細胞から脊髄運動ニューロンを簡便に作製する技術開発. 京都大学プレスリリース. 2017-02-07.
- 著者
- Uemura Norihito Koike Masato Ansai Satoshi Kinoshita Masato Ishikawa-Fujiwara Tomoko Matsui Hideaki Naruse Kiyoshi Sakamoto Naoaki Uchiyama Yasuo Todo Takeshi Takeda Shunichi Yamakado Hodaka Takahashi Ryosuke
- 出版者
- Public Library of Science
- 雑誌
- PLOS genetics (ISSN:15537404)
- 巻号頁・発行日
- vol.11, no.4, 2015-04-02
- 被引用文献数
- 59
パーキンソン病の解明に役立つメダカの作製に成功 -メダカが神経変性疾患の研究に貢献できる可能性- 京都大学プレスリリース. 2015-04-09.Homozygous mutations in the glucocerebrosidase (GBA) gene result in Gaucher disease (GD), the most common lysosomal storage disease. Recent genetic studies have revealed that GBA mutations confer a strong risk for sporadic Parkinson's disease (PD). To investigate how GBA mutations cause PD, we generated GBA nonsense mutant (GBA-/-) medaka that are completely deficient in glucocerebrosidase (GCase) activity. In contrast to the perinatal death in humans and mice lacking GCase activity, GBA-/- medaka survived for months, enabling analysis of the pathological progression. GBA-/- medaka displayed the pathological phenotypes resembling human neuronopathic GD including infiltration of Gaucher cell-like cells into the brains, progressive neuronal loss, and microgliosis. Detailed pathological findings represented lysosomal abnormalities in neurons and alpha-synuclein (α-syn) accumulation in axonal swellings containing autophagosomes. Unexpectedly, disruption of α-syn did not improve the life span, formation of axonal swellings, neuronal loss, or neuroinflammation in GBA-/- medaka. Taken together, the present study revealed GBA-/- medaka as a novel neuronopathic GD model, the pahological mechanisms of α-syn accumulation caused by GCase deficiency, and the minimal contribution of α-syn to the pathogenesis of neuronopathic GD.
- 著者
- Kondo Takayuki Funayama Misato Tsukita Kayoko Hotta Akitsu Yasuda Akimasa Nori Satoshi Kaneko Shinjiro Nakamura Masaya Takahashi Ryosuke Okano Hideyuki Yamanaka Shinya Inoue Haruhisa
- 出版者
- Elsevier B.V.
- 雑誌
- Stem Cell Reports (ISSN:22136711)
- 巻号頁・発行日
- 2014-06
- 被引用文献数
- 116
ヒトiPS細胞由来のグリア系神経前駆細胞移植でALSモデルマウスの生存期間を延長. 京都大学プレスリリース. 2014-06-27.