| Project/Area Number |
16H07185
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
Tsunemi Taiji 順天堂大学, 医学(系)研究科(研究院), 准教授 (50401344)
|
|---|
| Project Period (FY) |
2016-08-26 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | パーキンソン病 / Kufor-Rakeb症候群 / アルファシヌクレイン / エキソソーム / ATP13A2 / PARK9 / 遺伝学 / 神経科学 / 脳神経疾患 / 細胞・組織 / トランスレーショナルリサーチ / iPS細胞 / ドーパミン細胞 / ライソゾーム / αシヌクレイン / FYVEタンパク質 / ALIX / 脳・神経 |
|---|
| Outline of Final Research Achievements |
By screening FYVE proteins through in vitro invagination assay, “Protein A”, which is associated with ATP13A2/PARK9 was discovered. It is co-localized with ATP13A2 on endosomes, and the association of two proteins was determined by immunoprecipitation analysis. The localization of Protein A is altered in ATP13A2-deficient cells. The functional association between two proteins is under investigation.
At the early stage after the initiation of differentiation of dopaminergic neurons taken from patients with Kufor-Rakeb syndrome, the secretion of exosomes was already reduced. Lentiviral shRNA against ALIX enhanced the secretion of exosomes and attenuated alpha synuclein accumulation and abnormal mitochondrial respiration, suggesting that the main pathology of KRS involves the impaired exosome secretion, and therefore, improving this pathway would be beneficial to the issues observed in other intracellular organelles.
|
