Unveiling the Pathological Mechanisms and Developing New Treatment of Parkinsons Disease Caused by GBA1 Mutations
| Project/Area Number |
15H02540
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
木下 政人 京都大学, 農学研究科, 助教 (60263125)
秋山 央子 国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (80623462)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMAKADO Hodaka 京都大学, 大学院医学研究科, 助教 (10378771)
UEMURA Norihito 京都大学, 大学院医学研究科, 特定助教 (90749045)
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| Research Collaborator |
Ikuno Masashi 京都大学, 大学院医学研究科, 医員
Nakanishi Etsuro 京都大学, 大学院医学研究科, 医員
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥29,640,000 (Direct Cost: ¥22,800,000、Indirect Cost: ¥6,840,000)
Fiscal Year 2017: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2016: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2015: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
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| Keywords | パーキンソン病 / αシヌクレイン / 脂質 / GBA1 / メダカ / マウス / ゴーシェ病 / 脳神経疾患 |
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| Outline of Final Research Achievements |
We generated GBA2 and GBA3 knockout medaka by CRISPR/Cas9 system and crossed them with GBA1 knockout medaka. The analysis of the double and triple knockout medaka revealed that neither GBA2 nor GBA3 contributes to the pathophysiology in the central nervous system of GBA1 knockout medaka. However, we revealed the novel roles of GBA1 and GBA2 on the metabolism of cholesterol derivatives. The analysis of α-syn BAC Tg;GBA+/- mice revealed accumulation of phosphorylated α-syn in their brains and dopaminergic neuronal loss in the substantia nigra in an age-dependent manner. The low expression of mitochondrial complex I and accumulation of glucosylsphingosine may be associated with their pathophysiology.
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Report
(4 results)
Research Products
(44 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 Takahash
Organizer
Symposium for Young Neurologists and Emerging Researchers Grooming for Interaction and Excellence in Science (SYNERGIES)
Place of Presentation
マニラ
Year and Date
2016-03-10
Related Report
Int'l Joint Research
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