| Project/Area Number |
18H04041
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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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| Review Section |
Medium-sized Section 52:General internal medicine and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
秋山 央子 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (80623462)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥31,850,000 (Direct Cost: ¥24,500,000、Indirect Cost: ¥7,350,000)
Fiscal Year 2020: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2019: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2018: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
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| Keywords | パーキンソン病 / 多系統萎縮症 / αシヌクレイン / glucocerebrosidase |
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| Outline of Final Research Achievements |
Analysis of the two mice model for idiopathic Parkinson’s disease (PD), a-syn BAC Tg/GBA1 heterozygous KO mice and A53T mutant a-syn BAC Tg mice, revealed the region-specific increase in the amount of various kind of glycolipids, and cellular experiment suggested the conformational change of a-syn by altered lipid metabolism. To investigate the role of GBA2 gene as a modifier of GBA1 gene, we generated GBA2-/- (KO) medaka fish and GBA1/GBA2 double knockout medaka fish, and found that GBA2 deletion further increased the amount of specific glycolipids. Moreover, GBA1 was found to function as β-galactosidase, a GalCer degrading enzyme.
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| Academic Significance and Societal Importance of the Research Achievements |
モデル動物を使用した実験からパーキンソン病において脂質代謝異常がαシヌクレインの修飾を介して病態に関与しうること、孤発性パーキンソン病の最大の遺伝的リスク因子であるGBA１の修飾因子としてGBA2が存在することなどが判明し、治療のターゲット分子となりうることを示した。
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