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GPR55: Physiological functions and therapeutic potential in depression.

Yang Miao,Yuan-Yuan Cheng,Wei Guan

Published 2025 in Biochemical Pharmacology

ABSTRACT

Depression is a complex mental disorder characterised by persistent low mood and loss of interest in the outside world. By 2030, the global prevalence of depression is projected to reach 300 million, imposing a substantial burden on economic development and public health. G-protein coupled receptor 55 (GPR55) is a protein expressed in human cells that belongs to the superfamily of G protein-coupled receptors (GPCRs). Research has demonstrated that GPR55 plays a role in numerous physiological processes, including the regulation of energy metabolism, neural regulation, and cardiovascular regulation. However, its dysfunction contributes to the development of certain diseases, including cancer, neurological diseases, and metabolic disorders, making it a topic of growing interest in the field of scientific research. In recent years, GPR55 has garnered attention as an atypical cannabinoid receptor with potential relevance to depression. An increasing number of studies have indicated its potential as a therapeutic target for depression through mechanisms such as regulation of neuroinflammation, oxidative stress, and neurogenesis regulation. However, its precise role in depression pathogenesis remains unclear. This review systematically examines the role of GPR55 in depression pathogenesis and explores its potential as a target for antidepressant drugs. This is the first systematic review to focus on the neurobiological mechanisms underlying GPR55's role in depression regulation. This study also provides a theoretical basis for better understanding the role of GPR55 in depression pathogenesis.

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