2022 Fiscal Year Final Research Report
Generation of an aged Parkinson's disease brain model and elucidation of its pathophysiology using iPS cells
| Project/Area Number |
20K07873
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 52020:Neurology-related
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Keywords | パーキンソン病 / iPS細胞 / ドパミン神経 / アストロサイト / 老化 |
|---|
| Outline of Final Research Achievements |
Parkinson's disease is caused by midbrain dopaminergic neural loss and ageing is the most important pathogenic factor. This study aimed to explore the association between the ageing of dopaminergic nerves and astrocytes and Parkinson's disease pathology. We found that the pathological abnormality of dopaminergic neurons induced by iPS cells derived from hereditary Parkinson's disease patients was enhanced by using ageing-accelerating compounds, further clarifying the ageing-accelerating mechanism. We also established a method for inducing astrocytes derived from iPS cells and confirmed the activation of neuronal activity by co-culturing them with dopaminergic neurons. We also induced senescence in dopaminergic neurons and astrocytes under mixed culture conditions using a senescence-promoting compound, which may provide a model close to pathological conditions.
|
| Free Research Field |
脳神経内科
|
| Academic Significance and Societal Importance of the Research Achievements |
加齢性の神経変性疾患のひとつであるパーキンソン病について、患者由来iPS細胞を用いてその細胞老化を誘起することで病態異常発現が促進されることを発見し、その老化促進機序の一端を明らかにした。さらにiPS細胞由来ドパミン神経細胞とアストロサイトの共培養老化モデルを作製した。これらは新たな治療ターゲットとなる可能性があり、また今後の疾患病態解析に広く貢献できる可能性がある。
|
