G Protein–Coupled Receptors in Olfactory Signaling and Related Disorders: Mechanisms and Therapeutic Implications

ABSTRACT G protein–coupled receptors (GPCRs), the largest family of membrane proteins in mammals, are fundamental to olfactory signal transduction. By detecting odorant molecules and activating G protein–dependent and β‐arrestin–dependent signaling pathways, GPCRs regulate olfactory neuron depolarization, signal transmission, and adaptive modulation. This review comprehensively summarizes the molecular mechanisms of GPCRs in olfactory perception, signaling network regulation, and olfaction‐related disorders, including olfactory dysfunction, neurodegenerative diseases, and allergic inflammation. Furthermore, it highlights emerging therapeutic strategies such as biased ligands targeting GPCRs and stem cell–based interventions with clinical potential. Future investigations should prioritize elucidating the functions of orphan receptors and advancing precision therapeutic technologies to achieve breakthroughs in the diagnosis and treatment of olfaction‐related disorders.

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Publication Details

Journal
Sensory Neuroscience
Published
2026-03-11
DOI
https://doi.org/10.1002/sen2.70023
Primary Topic
Olfactory and Sensory Function Studies
Type
article
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0.00
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article

G Protein–Coupled Receptors in Olfactory Signaling and Related Disorders: Mechanisms and Therapeutic Implications

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Sensory Neuroscience
Olfactory and Sensory Function Studies
article

G Protein–Coupled Receptors in Olfactory Signaling and Related Disorders: Mechanisms and Therapeutic Implications

Chengzhilin Li, Fen Zhu, Ming Xia, Hongjie Du, Chengcheng Liu, Yuhan Dong, Fanyu Yuan, Wenwen Qi, Xu Guo, Zishuo Guo, Zhaoze Yang, Jian Liu
article en

Abstract

ABSTRACT G protein–coupled receptors (GPCRs), the largest family of membrane proteins in mammals, are fundamental to olfactory signal transduction. By detecting odorant molecules and activating G protein–dependent and β‐arrestin–dependent signaling pathways, GPCRs regulate olfactory neuron depolarization, signal transmission, and adaptive modulation. This review comprehensively summarizes the molecular mechanisms of GPCRs in olfactory perception, signaling network regulation, and olfaction‐related disorders, including olfactory dysfunction, neurodegenerative diseases, and allergic inflammation. Furthermore, it highlights emerging therapeutic strategies such as biased ligands targeting GPCRs and stem cell–based interventions with clinical potential. Future investigations should prioritize elucidating the functions of orphan receptors and advancing precision therapeutic technologies to achieve breakthroughs in the diagnosis and treatment of olfaction‐related disorders.

Sensory Neuroscience
Shandong Provincial Hospital (CN), Shandong First Medical University (CN)
Good health and well-being
Openalex Percentile: Top 23%
Olfactory and Sensory Function Studies
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