Examining the potential of miRNAs targeting ubiquitin ligase activity for Parkinson's disease treatment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Kobe University
• Principal Investigator: OMURA Tomohiro 神戸大学, 医学部附属病院, 准教授 (00439035)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: microRNA / ユビキチンリガーゼ / パーキンソン病

Outline of Final Research Achievements

Parkinson’s disease (PD) is a neurological disorder characterized by motor impairment. Current treatment approaches primarily address symptoms, necessitating the development of new drugs based on novel mechanisms of action. While we have conducted research on the relationship between HRD1 (ubiquitin ligase)/SEL1L (HRD1 stabilizer) and PD, recent evidence suggests the involvement of microRNAs (miRNAs) in the onset of PD.
In this study, we identified miR-101 as a miRNA that regulates SEL1L, and found that miR-101 exerts control over HRD1 expression by regulating SEL1L expression. Additionally, we observed that miR-101 affects neuronal cell death in a PD model. These results underscore the potential of miR-101 as a new therapeutic target for PD.

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

PDの診断・評価として日常生活動作等による評価法があるが、運動機能を客観的に評価することは難しい。今回、PDモデルにおいてmiR-101発現量が変化することを考慮すると、miR-101の発現量測定が運動機能を客観的に評価する新たなツールとなり得る可能性があり、臨床において極めて有用となり得る可能性がある。
また、miRNAを介してユビキチンリガーゼを制御する治療薬は多様な薬物が臨床応用されているPDでも存在せず、本成果を発展させることで、新たな神経疾患治療薬の創製の基礎となり得る可能性も提示できると考えられる。