Elucidation of mechanism that RNA G-quadruplex aggregation and its drug discovery in neurological diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08265
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Kumamoto University (2018); Gifu Pharmaceutical University (2016-2017)
• Principal Investigator: Shioda Norifumi 熊本大学, 発生医学研究所, 准教授 (00374950)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: グアニン四重鎖 / 神経変性疾患

Outline of Final Research Achievements

G-quadruplex (G4) structures are stacked nucleic acid structures that can form within G-rich DNA or RNA sequences. In the pathogenesis of neurodegenerative diseases, G4 structures are formed by guanine-rich repeats, which are transcribed, result in forms aggregates with several RNA binding proteins. In this study, we aimed to analyze the components of the RNA-G4/protein complex in the brain and to elucidate the abnormal aggregation mechanism in neurodegenerative diseases. We performed immunoprecipitation using a G4 structural recognition fragment, and identifiedsome novel G4-binding proteins and G4 formed mRNAs in mouse brain.

Free Research Field

神経科学、神経薬理学、核酸化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、神経変性疾患の病態に関与するRNA-G4構造/タンパク質複合体の神経細胞における構成成分を解析・同定した。今後、この異常凝集機構を解明することで、ALS等の神経変性疾患の病態解明に迫ることができ、新たな治療標的を提示できる。