GABAB Receptor: Structure, Biological Functions, and Therapy for Diseases
ABSTRACT Gamma‐aminobutyric acid (GABA) B receptors (GABABRs) that acts slowly and maintains the inhibitory tone are versatile regulators in the complex nervous behaviors and their involvement in various neuropsychiatric disorders, such as anxiety, epilepsy, pain, drug addiction, and Alzheimer'...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-05-01
|
| Series: | MedComm |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mco2.70163 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849736511567691776 |
|---|---|
| author | Weijie Xie Yuan Li Xinyue Wang Elena Blokhina Evgeny Krupitsky Marina Vetrova Ji Hu Ti‐Fei Yuan Jue Chen Hua Wang Xiangfang Chen |
| author_facet | Weijie Xie Yuan Li Xinyue Wang Elena Blokhina Evgeny Krupitsky Marina Vetrova Ji Hu Ti‐Fei Yuan Jue Chen Hua Wang Xiangfang Chen |
| author_sort | Weijie Xie |
| collection | DOAJ |
| description | ABSTRACT Gamma‐aminobutyric acid (GABA) B receptors (GABABRs) that acts slowly and maintains the inhibitory tone are versatile regulators in the complex nervous behaviors and their involvement in various neuropsychiatric disorders, such as anxiety, epilepsy, pain, drug addiction, and Alzheimer's disease. Additional study advances have implied the crucial roles of GABABRs in regulating feeding‐related behaviors, yet their therapeutic potential in addressing the neuropsychiatric disorders, binge eating, and feeding‐related disorders remains underutilized. This general review summarized the physiological structure and functions of GABABR, explored the regulation in various psychiatric disorders, feeding behaviors, binge eating, and metabolism disorders, and fully discussed the potential of targeting GABABRs and its regulator‐binding sites for the treatment of different psychiatric disorders, binge eating and even obesity. While agonists that directly bind to GABABR1 have some negative side effects, positive allosteric modulators (PAMs) that bind to GABABR2 demonstrate excellent therapeutic efficacy and tolerability and have better safety and therapeutic indexes. Moreover, phosphorylation sites of downstream GABABRs regulators may be novel therapeutic targets for psychiatric disorders, binge eating, and obesity. Further studies, clinical trials in particular, will be essential for confirming the therapeutic value of PAMs and other agents targeting the GABABR pathways in a clinical setting. |
| format | Article |
| id | doaj-art-09c32c46cf304663b16f8ac59c8c36a0 |
| institution | DOAJ |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-09c32c46cf304663b16f8ac59c8c36a02025-08-20T03:07:16ZengWileyMedComm2688-26632025-05-0165n/an/a10.1002/mco2.70163GABAB Receptor: Structure, Biological Functions, and Therapy for DiseasesWeijie Xie0Yuan Li1Xinyue Wang2Elena Blokhina3Evgeny Krupitsky4Marina Vetrova5Ji Hu6Ti‐Fei Yuan7Jue Chen8Hua Wang9Xiangfang Chen10Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center Tongji University School of Medicine Shanghai ChinaShanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center Shanghai Jiaotong University School of Medicine Shanghai ChinaShanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center Shanghai Jiaotong University School of Medicine Shanghai ChinaValdman Institute of Pharmacology Pavlov University St. Petersburg RussiaValdman Institute of Pharmacology Pavlov University St. Petersburg RussiaValdman Institute of Pharmacology Pavlov University St. Petersburg RussiaShanghaiTech University Shanghai ChinaShanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center Shanghai Jiaotong University School of Medicine Shanghai ChinaShanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center Shanghai Jiaotong University School of Medicine Shanghai ChinaDepartment of Oncology The First Affiliated Hospital of Anhui Medical University Hefei ChinaDepartment of Endocrinology Second Affiliated Hospital of Naval Medical University Shanghai ChinaABSTRACT Gamma‐aminobutyric acid (GABA) B receptors (GABABRs) that acts slowly and maintains the inhibitory tone are versatile regulators in the complex nervous behaviors and their involvement in various neuropsychiatric disorders, such as anxiety, epilepsy, pain, drug addiction, and Alzheimer's disease. Additional study advances have implied the crucial roles of GABABRs in regulating feeding‐related behaviors, yet their therapeutic potential in addressing the neuropsychiatric disorders, binge eating, and feeding‐related disorders remains underutilized. This general review summarized the physiological structure and functions of GABABR, explored the regulation in various psychiatric disorders, feeding behaviors, binge eating, and metabolism disorders, and fully discussed the potential of targeting GABABRs and its regulator‐binding sites for the treatment of different psychiatric disorders, binge eating and even obesity. While agonists that directly bind to GABABR1 have some negative side effects, positive allosteric modulators (PAMs) that bind to GABABR2 demonstrate excellent therapeutic efficacy and tolerability and have better safety and therapeutic indexes. Moreover, phosphorylation sites of downstream GABABRs regulators may be novel therapeutic targets for psychiatric disorders, binge eating, and obesity. Further studies, clinical trials in particular, will be essential for confirming the therapeutic value of PAMs and other agents targeting the GABABR pathways in a clinical setting.https://doi.org/10.1002/mco2.70163allosteric modulatorbinge eatingGABAB receptorsmetabolism disordersmolecular signalingpsychiatric disorders |
| spellingShingle | Weijie Xie Yuan Li Xinyue Wang Elena Blokhina Evgeny Krupitsky Marina Vetrova Ji Hu Ti‐Fei Yuan Jue Chen Hua Wang Xiangfang Chen GABAB Receptor: Structure, Biological Functions, and Therapy for Diseases MedComm allosteric modulator binge eating GABAB receptors metabolism disorders molecular signaling psychiatric disorders |
| title | GABAB Receptor: Structure, Biological Functions, and Therapy for Diseases |
| title_full | GABAB Receptor: Structure, Biological Functions, and Therapy for Diseases |
| title_fullStr | GABAB Receptor: Structure, Biological Functions, and Therapy for Diseases |
| title_full_unstemmed | GABAB Receptor: Structure, Biological Functions, and Therapy for Diseases |
| title_short | GABAB Receptor: Structure, Biological Functions, and Therapy for Diseases |
| title_sort | gabab receptor structure biological functions and therapy for diseases |
| topic | allosteric modulator binge eating GABAB receptors metabolism disorders molecular signaling psychiatric disorders |
| url | https://doi.org/10.1002/mco2.70163 |
| work_keys_str_mv | AT weijiexie gababreceptorstructurebiologicalfunctionsandtherapyfordiseases AT yuanli gababreceptorstructurebiologicalfunctionsandtherapyfordiseases AT xinyuewang gababreceptorstructurebiologicalfunctionsandtherapyfordiseases AT elenablokhina gababreceptorstructurebiologicalfunctionsandtherapyfordiseases AT evgenykrupitsky gababreceptorstructurebiologicalfunctionsandtherapyfordiseases AT marinavetrova gababreceptorstructurebiologicalfunctionsandtherapyfordiseases AT jihu gababreceptorstructurebiologicalfunctionsandtherapyfordiseases AT tifeiyuan gababreceptorstructurebiologicalfunctionsandtherapyfordiseases AT juechen gababreceptorstructurebiologicalfunctionsandtherapyfordiseases AT huawang gababreceptorstructurebiologicalfunctionsandtherapyfordiseases AT xiangfangchen gababreceptorstructurebiologicalfunctionsandtherapyfordiseases |