| Project/Area Number |
18K15463
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Ishikawa Kei-ichi 順天堂大学, 医学(系)研究科(研究院), 助教 (90733973)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | パーキンソン病 / iPS細胞 / 薬剤スクリーニング / 老化 / αシヌクレイン / 細胞老化 / ドーパミン神経細胞 / アルファシヌクレイン |
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| Outline of Final Research Achievements |
The dopaminergic neurons differentiated from iPS cells derived from hereditary Parkinson's disease (PD) patients (PARK2/4/6/9/22) were represented the pathological mechanism of PD such as their vulnerability, mitochondrial abnormality, abnormality of autophagy, α-synuclein accumulation. Four kinds of candidate compounds were identified by compound screening in PARK2/6-iPS cell-derived dopamine neurons. Furthermore, we reported that some dopaminergic neurons derived from sporadic PD-iPS cells also showed some common pathomechanisms and drug responsiveness with hereditary PD-iPS cells. We also analyzed the mechanism of senescence-promoting compounds in neuronal senescence, and reproduced the accumulation of α-synuclein in PARK4-iPS cell-derived neurons, which was difficult to reproduce in a short-term culture. This result indicates the relationship between senescence and PD pathology.
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝性パーキンソン病患者iPS細胞を用いて、患者神経における老化を含めた複数の病態機序を示すことができた。薬剤スクリーニングシステムを確立したこと、本システムにより治療候補化合物を見いだし、さらに孤発性パーキンソン病患者由来細胞でも一部は遺伝性と共通の異常を呈すること、さらに遺伝性パーキンソン病のスクリーニングから得られた治療候補化合物に同様の効果があることを示したことは、今後の新たな治療薬開発に繋がる成果である。
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