Elucidation of molecular mechanism of retrograde transport abnormality and neuronal cell death based on divalent iron dynamics
| Project/Area Number |
17K08311
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | パーキンソン病 / 鉄 / 二価鉄 / ２価鉄 / DMT1 / VPS35 / 逆行性輸送 / 脳神経疾患 / 薬理学 |
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| Outline of Final Research Achievements |
In this study, we used the organelle-specific Fe2 + fluorescent probe to visualize Fe2+ kinetics and elucidate the relationship between the perturbation of intracellular iron dynamics caused by the PD causative gene and the PD pathogenesis mechanism in order to develop a new drug discovery platform for PD. We have been able to clarify the disruption of Fe2+ dynamics caused by VPS35 and ATP13A2 knockdown. Moreover, it was clarified that the disturbance of Fe2+ dynamics caused by VPS35 knockdown was improved by R55, a retromer stabilizer.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで不明であった細胞内の鉄動態に関して、新しいプローブをしようすることで可視化することに成功し、パーキンソン病の病態の理解や創薬の関して新たな基盤を提供することができた。また、認知症を含む多くの神経変性疾患においてVPS35や逆行性輸送経路が注目されており、本研究成果は、パーキンソン病のみならず神経変性疾患全般に応用できる。
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Report
(4 results)
Research Products
(7 results)
