2022 Fiscal Year Final Research Report
Drug discovery research using Omura natural compounds and disease-specific iPS cells
Project/Area Number |
20K06914
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 46030:Function of nervous system-related
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Research Institution | Kitasato University |
Principal Investigator |
Ohta Etsuro 北里大学, 医療衛生学部, 准教授 (60508042)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | パーキンソン病 / LRRK2 / iPS細胞 / タウ / 創薬 |
Outline of Final Research Achievements |
In this study, we searched for developing novel therapeutic agents using Omura natural compounds and familial Parkinson's disease patient iPS cell-derived neurons harboring the I2020T mutant Leucine-Rich Repeat Kinase 2 (LRRK2). First, we constructed an automatic quantitative analysis system using IN Cell Analyzer 6000, which can evaluate shortening of neurite length, acceleration of apoptosis to oxidative stress, and increased Tau phosphorylation. Next, using this analysis system, 1st and 2nd screenings were performed, and 60 compounds were found that showed neurite length elongation and phosphorylated Tau suppression effects.
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Free Research Field |
神経科学
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Academic Significance and Societal Importance of the Research Achievements |
iPS細胞(iPSC)を用いた創薬研究では、新規治療薬となりうる候補薬剤がドラックリポジショニングの場合、治験への移行がスムーズに開始できることから、iPSC創薬の臨床応用への展開が注目されている。遺伝性パーキンソン病(PD)の原因分子LRRK2に変異をもつPD患者は、臨床症状や治療薬レボドパに対する反応性が孤発性PD患者と類似した特徴を示す。将来的な波及効果として、リード化合物の構造を変化させた合成化合物などアカデミア発iPSC創薬への展開が期待できる。また、Tauを標的とした化合物は、アルツハイマー病を含めた他の神経変性疾患への応用が期待できる。
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