| Project/Area Number |
16K09694
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
Yamasaki Ryo 九州大学, 医学研究院, 准教授 (10467946)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
山口 浩雄 九州大学, 大学病院, 特任講師 (00701830)
真崎 勝久 九州大学, 大学病院, 講師 (90612903)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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 | 多発性硬化症 / 実験的自己免疫性脳脊髄炎 / コネキシン / アストログリア / ミクログリア / オリゴデンドログリア / 動物モデル / マウスモデル |
|---|
| Outline of Final Research Achievements |
Our main purpose of this project is to investigate the cause of secondary-progressive multiple sclerosis (SPMS) using animal model for the development of new therapeutic options. In brain autopsied sample of SPMS patients, activation of glial cells and increase of gap junction proteins (= connexin, Cx) are observed. Focusing on this, we tried to analyze functions of Cxs on glial cells. Cx30 and Cx43 are mainly expressed in astroglia. Experimental autoimmune encephalomyelitis (EAE) which is known as an animal model for MS, in Cx30 deficient mice resulted in amelioration of chronic phase signs compared to wild type mice. In addition, in Cx43 astroglia-specific deficient mice, EAE was also ameliorated. From these findings, we found the clue for the development of new drugs for SPMS through the functional modification of Cxs.
|
| Academic Significance and Societal Importance of the Research Achievements |
多発性硬化症(MS)は若年女性に好発する中枢神経脱髄性疾患で、従来は欧米に多かったが、食生活の多様化やグローバリゼーションにより本邦でも患者数は増加傾向にある。MSの発症初期は再発寛解型の経過を取るが、十年以上経過すると二次進行形となり、現時点で治療方法がない。私達は、二次進行形MSにおけるグリア炎症に着目し、この時期の疾患メカニズム解明を目的とした。今回の研究で判明したコネキシンの疾患メカニズムにおける重要性は、同蛋白の機能阻害による二次進行形MSの新規治療薬創薬の足がかりとなる。
|
