Analysis of toxic heavy metals in neurodegenerative disorders and evaluation of derivatives of oleanoic acid as a therapeutic candidate
| Project/Area Number |
17K09164
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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 |
Hygiene and public health
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| Research Institution | Kitasato 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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | メチル水銀 / パーキンソン病 / オレアノール酸配糖体 / 重金属 / 脳神経系変性疾患 / 環境汚染物質 |
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| Outline of Final Research Achievements |
Neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD) causes occur sporadically and it is generally agreed that they could arise through interactions among genetic and environmental factors. Methylmercury (MeHg), a neurotoxic metal, is considered to one of the major environmental hazards for neurodegenerative disorders. In this research project, we investigated whether there is an interaction between MeHg and neurodegenerative disorders. In addition, we tried to create oleanolic acid (OA) 3 -ortoester derivatives as anti-AD or anti-PD drug candidates. We found that overexpression of α-synuclein showed high sensitivity to MeHg compared to wild type cells. Treatment of OA-3-glucoside attenuated MeHg-induced α-synuclein-overexpressed cell death.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果から、パーキンソン病の原因遺伝子であるαシヌクレインの高発現細胞細胞はメチル水銀のばく露に対し脆弱であることがわかった。すなわち、パーキンソン病発症後における神経細胞の脱落にメチル水銀のばく露がリスク因子となることが考えられる。また、オレアノール酸配糖体の中でOA3-Gluはメチル水銀の毒性を緩和することを考えると、αシヌクレインが蓄積しているパーキンソン病の神経細胞をメチル水銀から保護する化合物となる可能性がある。
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Report
(4 results)
Research Products
(20 results)
