Orphan G Protein Coupled Receptors in Affective Disorders

Watkins, Lyndsay R.; Orlandi, Cesare

doi:10.3390/genes11060694

Cited by 46 publications

(32 citation statements)

References 237 publications

(454 reference statements)

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“…Interestingly, while the GO terms such as G protein−coupled amine receptor activity and G protein−coupled serotonin receptor activity were specifically enriched with M1 module genes, the GO terms such as ligand-gated ion channel activity and ionotropic glutamate receptor activity were specifically enriched with M5 module genes ( Figure 3 A). These metabotropic and ionotropic receptors have been reported to be essential for various aspects of the nervous system functions [ 38 ], many of which have been associated with the pathophysiology of various psychiatric disorders [ 39 , 40 ]. Thus, our study provides mechanistic insights indicating the important role of neuronal receptor dysregulation in the pathophysiology of delirium, and the separate functional characterization of the two modules may provide information regarding the different aspects of delirium mechanisms associated with the M1 and M5 modules.…”

Section: Discussionmentioning

confidence: 99%

Systems Level Analysis and Identification of Pathways and Key Genes Associated with Delirium

Takahashi

Terada

Muto

2020

Genes

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Delirium is a complex pathophysiological process, and multiple contributing mechanisms have been identified. However, it is largely unclear how the genes associated with delirium contribute and which of them play key roles. In this study, the genes associated with delirium were retrieved from the Comparative Toxicogenomics Database (CTD) and integrated through a protein–protein interaction (PPI) network. Delirium-associated genes formed a highly interconnected PPI subnetwork, indicating a high tendency to interact and agglomerate. Using the Molecular Complex Detection (MCODE) algorithm, we identified the top two delirium-relevant network modules, M1 and M5, that have the most significant enrichments for the delirium-related gene sets. Functional enrichment analysis showed that genes related to neurotransmitter receptor activity were enriched in both modules. Moreover, analyses with genes located in human accelerated regions (HARs) provided evidence that HAR-Brain genes were overrepresented in the delirium-relevant network modules. We found that four of the HAR-Brain genes, namely APP, PLCB1, NPY, and HTR2A, in the M1 module were highly connected and appeared to exhibit hub properties, which might play vital roles in delirium development. Further understanding of the function of the identified modules and member genes could help to identify therapeutic intervention targets and diagnostic biomarkers for delirium.

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Section: Discussionmentioning

confidence: 99%

Systems Level Analysis and Identification of Pathways and Key Genes Associated with Delirium

Takahashi

Terada

Muto

2020

Genes

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“…On the contrary, it was reported that KYNA did not modulate the α7nAchR activities in the hippocampus of the adult mouse brain [22]. KYNA activates the orphan G-protein receptor 35 (GPR35) expressed in the glia and neurons of the hippocampus, which inhibits the adenylate cyclase and depresses excitability and synaptic transmission in the hippocampus [23]. In addition, KYNA decreased body weight without negative influence on densitometry and mandibular bone [24].…”

Section: Figurementioning

confidence: 97%

Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway

Török

Tanaka

Vécsei

2020

Preprint

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Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer’s diseases, Parkinson’s disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of the KP alteration observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota to the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.

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“…Several studies, including genetic loss of function studies, indicate a role for orphan GPCRs, namely ADGRB2 (BAI2) [130], GPR3 [131], GPR26 [132], GPR37 [133,134], and GPR158 [135] in the regulation of emotional behavior. The contribution of orphan GPCRs to the modulation of mood behavior has been extensively reviewed recently [136]. However, the influence of early stress on orphan GPCR expression and function, as well as the role of orphan GPCRs in mechanistically programming persistent alterations in emotionality that arise following early stress, remains poorly understood.…”

Section: Contribution Of G Protein-coupled Receptors To the Effects Omentioning

confidence: 99%

GPCR signaling: role in mediating the effects of early adversity in psychiatric disorders

et al. 2021

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Early adversity is a key risk factor for the development of several psychiatric disorders, including anxiety and depression. During early life, neurocircuits that regulate emotionality undergo substantial structural remodeling and functional maturation, and are thus particularly susceptible to modification by environmental experience. Preclinical evidence indicates that early stress enhances adult anxio-depressive behaviors. A commonality noted across diverse early stress models is life-long alterations in neuroendocrine stress responses and monoaminergic neurotransmission in key limbic circuits. Dysregulation of G protein-coupled receptor (GPCR) signaling is noted across multiple early stress models and is hypothesized to be an important player in the programming of aberrant emotionality. This raises the possibility that disruption of GPCR signaling in key limbic regions during critical temporal windows could establish a substrate for enhanced risk of adult psychopathology. Here, we review literature, predominantly from preclinical models, which supports the building hypothesis that a disruption of GPCR signaling could play a central role in programming persistent molecular, cellular, functional, and behavioral changes as a consequence of early adversity.

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Orphan G Protein Coupled Receptors in Affective Disorders

Cited by 46 publications

References 237 publications

Systems Level Analysis and Identification of Pathways and Key Genes Associated with Delirium

Systems Level Analysis and Identification of Pathways and Key Genes Associated with Delirium

Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway

GPCR signaling: role in mediating the effects of early adversity in psychiatric disorders

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