G protein-coupled receptors and diseases: signal crosstalk and therapeutics

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09813
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Iiri Taroh 聖マリアンナ医科大学, 医学部, 教授 (90313022)
• Research Collaborator: MAKITA noriko ; SATO Junichiro ; MANAKA katsunori ; MITANI koji ; OOTAKI masanori ; TAKEBA yuko ; OHTA yuki ; WATANABE minoru ; MATSUMOTO naoki ; OHWADA tomohiko
• Project Period (FY): 2016-10-21 – 2019-03-31
• Keywords: 内分泌学 / Gタンパク質共役受容体 / GPCR / クロストーク / 疾患解析制御 / バイアスアゴニズム

Outline of Final Research Achievements

G protein-coupled receptors (GPCRs) and their crosstalks may play an important role in fine-tuning of many signals in our body, and their signal unbalance may underlie many disease states. In this study, 1) we have screened and analyzed molecular defects of GPCRs in diseases and tried to rescue them using small molecules targeting GPCRs in vitro and also in patients. 2) We have also designed analogues of small molecules that nitrosyl ate and thereby inactivate GRK2 (G protein-coupled receptor kinase 2 that plays an essential role in many GPCR desensitization) and analyzed their effects on lipolysis of adipocytes. 3)We have also analyzed molecular action of GPCRs by combining accumulated data based on G protein/GPCR disease analysis and structural information.

Free Research Field

内分泌学、分子生物学、内科学、薬理学、GPCRシグナル制御と疾患

Academic Significance and Societal Importance of the Research Achievements

GPCRとそのクロストークの分子異常に基づく疾患の解析と小分子化合物による制御、in silicoを含めた制御ツール開発は、疾患メカニズム解明とともにGPCR研究における普遍的示唆を与えることが期待され、さらには新たな創薬へと結実することが期待される。