| Project/Area Number |
18K06494
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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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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | Okinawa Institute of Science and Technology Graduate University |
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Principal Investigator |
Guillaud Laurent 沖縄科学技術大学院大学, 分子神経科学ユニット, グループリーダー (90596222)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | liquid phase separation / ATP / synapse / neurodegeneration / Liquid phase separation / Synapse / Mitochondria / Neurodegeneration / synaptic vesicle / active zone / cytosol / solubility / Neuroscience / Trafficking / Imaging |
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| Outline of Final Research Achievements |
Here, I present compelling evidences showing that intracellular concentration ATP produced by active mitochondria in mouse and human neurons is pivotal to maintain the presynaptic release machinery and axonal proteins solubility via liquid phase separation (LPS). Fluorescence recovery after photobleaching experiments demonstrate that decrease in intracellular ATP after mitochondria inhibition, leads to condensation of axo-terminal cytosol, synaptic vesicles, and active zone components and control the functional organization of mouse calyceal synapses. In vitro experiments on purified proteins involved in PD, AD and ALS show they all undergo ATP concentration-dependent LPS at different ATP concentration. Human iPSC-derived neurons from PD and ALS patients show consistent reduction in axonal cytosol fluid phase correlated with significant reduction in intracellular ATP.
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| Academic Significance and Societal Importance of the Research Achievements |
Future research to improve mitochondria activity and ATP production might contribute to the development of novel therapeutics to prevent or alleviate protein aggregation before the apparition of severe synaptic defects and pathological symptoms in PD, AD or ALS.
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