Clarification of pathophysiological roles of MIDN, a novel genetic risk factor for Parkinson's disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06681
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Yamagata University
• Principal Investigator: OBARA YUTARO 山形大学, 医学部, 教授 (40400270)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: パーキンソン病 / Midnolin (MIDN)

Outline of Final Research Achievements

Our previous molecular epidemiological study in Yamagata, Japan revealed that Midnolin (MIDN) variants were correlated to Parkinson’s disease. In this study, we reanalyzed molecular epidemiological data in a large British population cohort, and replicated the correlation between MIDN variants and Parkinson’s disease as observed in Yamagata, suggesting MIDN is a universal genetic risk factor. We examined the molecular mechanism of MIDN gene expression and found that transcription factors including TFAP2 and AP-1 bound to specific sites upstream of the MIDN gene and regulated the transcription. As a phenotype of Midn knockout mice, the projection of dopaminergic neurons from midbrain to striatum was largely inhibited in knockout mice.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病は厚労省が指定する特定疾患の中でも特に患者数が多い神経難病であるが、その明確な発症機序や根本的な治療法が確立されていない。MIDN遺伝子は2000年に初めて報告されたが、その遺伝子産物の機能や病気との関連性はほとんど不明だった。我々がMIDNの遺伝子異常とパーキンソン病が関連し、その発症メカニズムを部分的に解明出来たのは新しい発見であり、学術的な独創性が高いと思われる。また、MIDNの発現制御機構が明らかになったため、MIDNを利用した新しい作用機序を有する抗パーキンソン病薬の開発に貢献出来る可能性があり、将来的な創造性、応用性が期待される。