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GPR91, a critical signaling mechanism in modulating pathophysiologic processes in chronic illnesses
Xinyi Li1, Li Xie1, Xiangli Qu2,3
1Department of Medical Microbiology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Summary
The succinate receptor GPR91, activated by the metabolite succinate, plays a key role in inflammation and disease. Targeting this pathway offers potential for treating chronic illnesses like diabetes and inflammatory bowel disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Succinate receptor GPR91 is a G protein-coupled receptor (GPCR) activated by succinate, a metabolic intermediate.
- GPR91 activation influences innate immunity, inflammation, tissue repair, and oncogenesis.
Purpose of the Study:
- To explore the role of the succinate-GPR91 axis in various pathophysiological conditions.
- To understand the molecular basis of chronic illnesses linked to GPR91 signaling.
Main Methods:
- 3D crystal structure illustration of GPR91.
- Discovery and analysis of GPR91 antagonists.
- Dissection of succinate-GPR91-G protein signaling pathways.
Main Results:
- GPR91's involvement in chronic diseases including hypertension, diabetes, fatty liver disease, inflammatory bowel disease, and cancer.
- Elucidation of GPR91-ligand binding modes with agonists and antagonists.
Conclusions:
- The succinate-GPR91 axis is critically involved in numerous chronic illnesses.
- Targeting the succinate-GPR91 pathway with small molecule antagonists presents a therapeutic strategy.
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