| Project/Area Number |
17K07098
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Nerve anatomy/Neuropathology
|
|---|
| Research Institution | Nagasaki University |
|---|
Principal Investigator |
MATSUMOTO Gen 長崎大学, 医歯薬学総合研究科(医学系), 講師 (50415303)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 神経変性疾患 / 選択的オートファジー / アグリソーム / アシルドーパミン / p62 / タンパク質凝集体 / アグリファジー / p62/sqstm1 / タンパク質凝集 / 脳神経疾患 |
|---|
| Outline of Final Research Achievements |
As neuronal accumulation of ubiquitinated protein aggregates is the common pathology of many neurodegenerative diseases, disruption of the proteolytic mechanism has been considered as a cause of the neurodegeneration. In this research, we found that acyldopamines, a brain substance, induce the expression of p62 and promotes the aggresome formation without inhibiting protein degradation, suggesting that protein aggregates can be generated without disruption of the protein degradation systems. Furthermore, we also found compounds that promote S403 phosphorylation of p62 without aggresome formation. The enhanced p62 phosphorylation by the compound treatment induces the degradation of intracellular protein aggregates through aggrephagy pathway. The discovery of the compounds may lead to novel therapeutical drug discovery for several neurodegenerative diseases.
|
| Academic Significance and Societal Importance of the Research Achievements |
神経変性疾患におけるタンパク質凝集体の形成は、タンパク質分解機構の変容が原因の一つであると考えられてきたが、本研究で明らかになったアシルドーパミンによるアグリソーム形成促進効果は、特にグリア細胞における凝集体形成を説明するものであり、いくつかの神経変性疾患の病態形成のメカニズム解明に寄与するものと思われる。
|
