Analyzing the pathogenesis of neurodegenerative diseases using medaka with multigene mutations.
| Project/Area Number |
26670442
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Kyoto University |
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Principal Investigator |
Takahashi Ryosuke 京都大学, 医学(系)研究科(研究院), 教授 (90216771)
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| Co-Investigator(Renkei-kenkyūsha) |
UEMURA Norihito 京都大学, 大学院医学研究科, 特定助教 (90749045)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | パーキンソン病 / メダカ / α‐シヌクレイン / GBA / α-シヌクレイン |
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| Outline of Final Research Achievements |
Parkinson’s disease (PD) is pathologically characterized by dopaminergic neuron loss and intraneuronal α-synuclein (α-syn) aggregates. Recent genetic studies have revealed that GBA mutations confer a strong risk for PD. In the present study, we generated and analyzed GBA nonsense mutant (GBA－/－) medaka. In contrast to the perinatal death in other species lacking GBA, GBA－/－ medaka survived for months, enabling analysis of the pathological progression. Pathological findings represented α-syn accumulation in their brains, which was caused by the impairment of autophagy-lysosome pathway. Furthermore, we generated α-syn deletion mutant medaka and human α-syn transgenic medaka. We crossed them with GBA mutant medaka respectively, but these double mutant medaka did not displayed any pathological changes. From these results, this study could not elucidate the pathological role of α-syn in GBA－/－ medaka.
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] Viable neuronopathic Gaucher disease model in medaka (Oryzias latipes) displays axonal accumulation of alpha-synuclein2015
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
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Journal Title
PLoS Genetics
Volume: 11
Issue: 4
Pages: 1-14
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway.2015
Author(s)
Imai Y, Kobayashi Y, Inoshita T, Meng H, Arano T, Uemura K, Asano T, Yoshimi K, Zhang CL, Matsumoto G, Ohtsuka T, Kageyama R, Kiyonari H, Shioi G, Nukina N, Hattori N, Takahashi R
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Journal Title
PLoS Genet.
Volume: 11
Issue: 9
Pages: e1005503-e1005503
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] Pathological studies in Parkinson's disease2016
Author(s)
Seiji Kaji, Norihito Uemura, Takakuni Maki, Makoto Urushitani, Ryosuke Takahashi
Organizer
Symposium for Young Neurologists and Emerging Researchers Grooming for Interaction and Excellence in Science (SYNERGIES)
Place of Presentation
Manila
Year and Date
2016-03-10
Related Report
Int'l Joint Research
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