The mechanism of metabolic and autophagic dysfunction in optic nerve degeneration
| Project/Area Number |
18K09427
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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 56060:Ophthalmology-related
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
Kitaoka Yasushi 聖マリアンナ医科大学, 医学研究科, 教授 (10367352)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | オートファジー / 緑内障 / nicotinamide / SIRT1 / p38 / nicotinamide riboside / NRK1 / NAD / 視神経 / TNF / p62 / Sirtuin / autophagy |
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| Outline of Final Research Achievements |
Autophagic and metabolic function may decrease in aging. We previously reported the impairment of autophagic flux in optic nerve in glaucomatous optic neuropathy model. Thus, in the present term, we tested if some autophagy activators alter axon loss in tumor necrosis factor (TNF)-induced optic nerve degeneration. First, we found that a SIRT1 activator enhanced autophagic flux and exerted axonal protection. Second, exogenous nicotinamide riboside (NR) upregulated endogenous nicotinamide riboside kinase 1 (NRK1) and SIRT1 expression in optic nerve. NR also enhanced autophagic flux and exerted axonal protection. We also found NRK1 exists in RGCs and optic nerve fibers. Third, we found upregulation of phosphorylated p38 in optic nerve axons in TNF-induced optic nerve degeneration. Upregulated p-p38 may inhibit autophagy. Akebia saponin D, an autophagy activator, prevented the increment of p-p38, enhanced autophagy flux, and exerted axonal protection.
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| Academic Significance and Societal Importance of the Research Achievements |
オートファジーや代謝機能は加齢により低下するが、運動や食事制限はオートファジー活性につながる。しかし高齢者にそれらは困難であり、薬物でのオートファジー活性化や軸索保護を提供できることにつながる研究成果を得たと考えている。
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Report
(4 results)
Research Products
(13 results)
