| Project/Area Number |
24790756
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
TAKAMI Yoichi 大阪大学, 医学(系)研究科(研究院), 助教 (90621756)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAMI Hironori 大阪大学, 大学院医学系研究科 健康発達医学 (20325369)
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| Co-Investigator(Renkei-kenkyūsha) |
KANEDA Yasufumi 大阪大学, 大学院医学系研究科 遺伝子治療学 (10177537)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | αシヌクレイン / 血管内皮機能 / 老化 / 動脈硬化 / インスリン抵抗性 / 炎症 / NFｋB / eNOS / メタボリック症候群 / 糖代謝 / 細胞老化 / NFκB |
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| Outline of Final Research Achievements |
The physiological roles of α-synuclein (SNCA), one of the causative genes of Parkinson’s disease, remain to be identified. SNCA was found to be secreted from endothelial cells (EC) and the human population study showed inverse correlation of serum SNCA levels with insulin resistance, high blood pressure and aging. Recombinant SNCA (rSNCA) promotes glucose uptake in the adipose tissues and skeletal muscles through the LPAR2/Gab1/PI3K/Akt pathway. rSNCA induces eNOS activation and NO production in EC via Gab1/PI3K/Akt pathway followed by cGMP production in co-cultured vascular smooth muscle cells. Aortas from SNCA KO show impairment of Ach-induced relaxation due to eNOS dysfunction. Treatment with rSNCA displays NFκB inactivation in EC and in vivo study of SNCA/ApoE double-knockout mice shows exaggerated expression of inflammatory genes in aortas. These functions of SNCA represent a new insight of aging-related metabolic syndrome and the cardiovascular complications.
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