Analysis of epigenetic modification in parkinson's disease patient-specific iPSCs-derived dopamine neurons

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08280
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Hoshi University
• Principal Investigator: Kuzumaki Naoko 星薬科大学, 薬学部, 准教授 (10507669)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: パーキンソン病 / iPS 細胞 / ドパミン神経 / エピジェネティクス

Outline of Final Research Achievements

In Parkinson's disease, it has been widely accepted that the continuous loss of dopamine (DA) neurons in the substantia nigra leads to movement disorders. However, the mechanism that underlies the selective loss of DA neurons in Parkinson's disease is not fully understood. In this study, we found a dramatic increase in catechol-O-methyltransferase (COMT) along with a decrease in DNA methylation levels in Parkinson’s disease-specific iPSC-derived DA neurons. Furthermore, in the cell-specific in vivo study, overexpression of COMT in DA neurons of the substantia nigra of dopamine transporter-Cre mice produced cataleptic behaviors accompanied by impaired motor coordination. These findings suggest that increase of COMT, with its epigenetic modification, in dopaminergic neurons may result in the dysfunction of synaptic DA transmission in the initial process of Parkinson's disease.

Free Research Field

幹細胞薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究において、疾患特異的 iPS 細胞技術や神経科学的アプローチに従って、黒質ドパミン神経におけるエピジェネティック修飾を伴った COMT の発現増加を見出し、こうしたドパミン神経特異的 COMT の発現増加は、ドパミン神経の機能障害に関与する可能性を明らかとした。このような結果は、パーキンソン病態の初期段階を反映していることが考えられるため、初期段階における治療法の開発の一助となる可能性が示唆された。