The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment—A Narrative Review

Kryszkowski, Waldemar; Boczek, Tomasz

doi:10.3390/jcm10071475

Cited by 5 publications

(3 citation statements)

References 168 publications

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“…The involvement of mGluRs in various neurological and psychiatric disorders highlights their potential as therapeutic targets. In brief, for schizophrenia, there is strong evidence from several preclinical studies indicating that representatives of all three groups of mGluRs may be important in treating schizophrenia and are associated with improvement in both cognitive and non-cognitive functions [ 33 ]. It is notable that mGluR subtype distribution correlates with brain regions associated with schizophrenia [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…In brief, for schizophrenia, there is strong evidence from several preclinical studies indicating that representatives of all three groups of mGluRs may be important in treating schizophrenia and are associated with improvement in both cognitive and non-cognitive functions [ 33 ]. It is notable that mGluR subtype distribution correlates with brain regions associated with schizophrenia [ 33 , 34 ]. Importantly, for bipolar disorder (BD), post-mortem examination of brain tissue from patients with BD have previously reported reduced expression of (the ionotropic glutamate) NMDA receptor subunits and receptor-associated proteins in the hippocampus [ 35 ] and dorsolateral prefrontal cortex [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

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Rare recurrent copy number variations in metabotropic glutamate receptor interacting genes in children with neurodevelopmental disorders

Glessner

Khan

Chang

et al. 2023

J Neurodevelop Disord

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Background Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy. Methods Platforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD (n = 7920), ASD (n = 4318), or both (n = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case–control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity. Results Here, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein–protein interaction with mGluR 1–8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases (P = 3.22E − 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls (P = 5.26E − 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls (P = 4.08E − 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls (P = 9.21E − 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records. Conclusion Together, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4, 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD. Trial registration ClinicalTrials.gov Identifier: NCT02286817 First Posted: 10 November 14, ClinicalTrials.gov Identifier: NCT02777931 first posted: 19 May 2016, ClinicalTrials.gov Identifier: NCT03006367 first posted: 30 December 2016, ClinicalTrials.gov Identifier: NCT02895906 first posted: 12 September 2016.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rare recurrent copy number variations in metabotropic glutamate receptor interacting genes in children with neurodevelopmental disorders

Glessner

Khan

Chang

et al. 2023

J Neurodevelop Disord

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“…An intriguing topic for future studies is the evaluation of the role of mGluR homodimerization and/or heterodimerization in cancer development and progression. There are numerous antagonists and agonists for group I–III mGluRs, which have been extensively reviewed by multiple authors; therefore, they will not be reviewed here [ 20 , 31 , 32 , 33 , 34 ].…”

Section: Metabotropic Glutamate Receptor Biologymentioning

confidence: 99%

Implications of a Neuronal Receptor Family, Metabotropic Glutamate Receptors, in Cancer Development and Progression

Eddy

Eddin

Fateeva

et al. 2022

Cells

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Cancer is the second leading cause of death, and incidences are increasing globally. Simply defined, cancer is the uncontrolled proliferation of a cell, and depending on the tissue of origin, the cancer etiology, biology, progression, prognosis, and treatment will differ. Carcinogenesis and its progression are associated with genetic factors that can either be inherited and/or acquired and are classified as an oncogene or tumor suppressor. Many of these genetic factors converge on common signaling pathway(s), such as the MAPK and PI3K/AKT pathways. In this review, we will focus on the metabotropic glutamate receptor (mGluR) family, an upstream protein that transmits extracellular signals into the cell and has been shown to regulate many aspects of tumor development and progression. We explore the involvement of members of this receptor family in various cancers that include breast cancer, colorectal cancer, glioma, kidney cancer, melanoma, oral cancer, osteosarcoma, pancreatic cancer, prostate cancer, and T-cell cancers. Intriguingly, depending on the member, mGluRs can either be classified as oncogenes or tumor suppressors, although in general most act as an oncogene. The extensive work done to elucidate the role of mGluRs in various cancers suggests that it might be a viable strategy to therapeutically target glutamatergic signaling.

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Grundlagen der Neuro-/Psychopharmakologie

Gerlach,

Drepper

2023

Neuro-/Psychopharmaka Im Kindes- Und Jugendalter

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The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment—A Narrative Review

Cited by 5 publications

References 168 publications

Rare recurrent copy number variations in metabotropic glutamate receptor interacting genes in children with neurodevelopmental disorders

Rare recurrent copy number variations in metabotropic glutamate receptor interacting genes in children with neurodevelopmental disorders

Implications of a Neuronal Receptor Family, Metabotropic Glutamate Receptors, in Cancer Development and Progression

Grundlagen der Neuro-/Psychopharmakologie

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