| Project/Area Number |
16K09675
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
Hatano Taku 順天堂大学, 医学(系)研究科(研究院), 准教授 (60338390)
|
|---|
| 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | パーキンソン病 / PARK14 / PLA2G6 / α-シヌクレイン / リノール酸 / リン脂質代謝 / レヴィ小体 / リン脂質 / C19orf72 / 脂質代謝異常 / 放出機能 / シナプス終末 / Lewy小体 |
|---|
| Outline of Final Research Achievements |
PLA2G6 is known as the causative gene of familial Parkinson's disease (PARK14). Pathological studies of PARK14 revealed dopaminergic neuronal degeneration with Lewy bodies (LB). Thus, impairment of PLA2G6 may be associated with the aggregation of alpha-synuclein (AS). To reveal the association between PLA2G6 dysfunction and AS aggregation, PLA2G6 knockout Drosophila was generated and exhibited motor and sleep dysfunction due to dopaminergic neuronal degeneration. Additionally, the fly model had synaptic terminal dysfunction. These phenotypes were rescued by overexpression of wild type human PLA2G6 but not A80T pathogenic mutation. Furthermore, I found an alteration in lipid composition and AS aggregation in the brain of the fly model. Administration of linoleic acid could rescue the phenotypes and AS aggregation. Therefore, lipid composition in the brain may be critical for the mechanisms of LB formation and lipid administration therapy might have an effect on Parkinson's disease.
|
| Academic Significance and Societal Importance of the Research Achievements |
α-シヌクレイン(AS)は脂質膜、中でもリン脂質に直接結合する事が知られている。膜への結合能の変化はAS凝集に関連し神経変性の原因となる。本研究でリン脂質代謝障害とAS凝集との関連を明らかにしており、パーキンソン病（PD）の病態解明につながる成果を挙げた。さらに、脂質補充をすることで脂質膜を変化させAS凝集を抑制し、神経変性を改善させる事を明らかにした。これにより適切な脂質を摂取する食事療法による治療への応用、つまりは医食同源を実現できる可能性を示した研究である。神経難病であるPDの病態解明として、脂質酵素に焦点を当て治療への応用を検討しており、学術的および社会的意義が高い研究である。
|
