| Project/Area Number |
16K07076
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | Tokyo Metropolitan Institute of Medical Science |
|---|
Principal Investigator |
GUO Xiaoli 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 主任研究員 (50443114)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | グリア細胞 / ASK1 / Astrocyte / Microglia/macrophage / cross-talk / 多発性硬化症 / 視神経炎 / レニン・アンジオテンシン系 / M1 microglia / A1 astrocyte / cytokine/chemokine / 神経保護 / 緑内障 / カロリー制限 |
|---|
| Outline of Final Research Achievements |
We generated four lines of cell-specific ASK1 knockout mice to examine the roles of ASK1 during EAE. ASK1 signaling in microglia/macrophages induces a pro-inflammatory phenotype in microglia/macrophages, which subsequently promotes the activation of astrocytes. Also, ASK1 signaling in astrocytes stimulated the production of key inflammatory mediators that further activated microglia/macrophages. Neuroinflammation was reduced from the early stages of EAE in in microglia/macrophage-specific ASK1 knockout mice, while only the late-phase neuroinflammation was ameliorated in astrocyte-specific ASK1 knockout mice.
We also found that the Renin-Angiotensin System regulates neuro-degeneration in a mouse model of optic neuritis and demonstrated that caloric restriction promotes cell survival in a mouse model of normal tension glaucoma.
|
| Academic Significance and Societal Importance of the Research Achievements |
ASK1の細胞特異的な機能や既存薬剤による治療研究から網膜および視神経変性疾患など難病の発症メカニズムを解明し、治療法の開発に有用な情報を提供した。特にMSによる視神経変性に対する治療薬の開発に有用である。
我々の研究成果を参考にASK1阻害剤がTocris社から発売された。また研究成果は研究所HPや医学専門websiteでも紹介されている。中国での招待講演でも研究発表を行うなど、研究成果を積極的に社会に公開する。
|
