Serum Epidermal Growth Factor is Low in Schizophrenia and Not Affected by Antipsychotics Alone or Combined With Electroconvulsive Therapy

Zhang, Xiaobin; Xiao, Wenhuan; Chen, Kuan‐Yu; Zhao, Youwei; Ye, Fei; Tang, Xiaowei; Du, Xiangdong

doi:10.3389/fpsyt.2020.00104

Cited by 9 publications

(5 citation statements)

References 30 publications

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“…The D3 receptor is able to interact with nicotinic receptors (for instance alpha 4 containing nicotinic receptors) in particular in VTA ( Bontempi et al., 2017 ) and represents a main point of cross talk with the cholinergic system ( Matera et al., 2019 ). D3 turnover is controlled by the EGFR tyrosine kinase signaling cascade ( Zhang et al., 2020 ). EGFR phosphorylates GRK2 which then phosphorylates the intracellular domain of the D3 receptor to trigger D3 intracellular receptor degradation ( Sun et al., 2018 ).…”

Section: Section 1: Dopamine Receptorsmentioning

confidence: 99%

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Martel¹,

McArthur²

2020

Front. Pharmacol.

177

125

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Dopamine receptors are widely distributed within the brain where they play critical modulator roles on motor functions, motivation and drive, as well as cognition. The identification of five genes coding for different dopamine receptor subtypes, pharmacologically grouped as D1- (D1 and D5) or D2-like (D2S, D2L, D3, and D4) has allowed the demonstration of differential receptor function in specific neurocircuits. Recent observation on dopamine receptor signaling point at dopamine—glutamate-NMDA neurobiology as the most relevant in schizophrenia and for the development of new therapies. Progress in the chemistry of D1- and D2-like receptor ligands (agonists, antagonists, and partial agonists) has provided more selective compounds possibly able to target the dopamine receptors homo and heterodimers and address different schizophrenia symptoms. Moreover, an extensive evaluation of the functional effect of these agents on dopamine receptor coupling and intracellular signaling highlights important differences that could also result in highly differentiated clinical pharmacology. The review summarizes the recent advances in the field, addressing the relevance of emerging new targets in schizophrenia in particular in relation to the dopamine – glutamate NMDA systems interactions.

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Section: Section 1: Dopamine Receptorsmentioning

confidence: 99%

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Martel¹,

McArthur²

2020

Front. Pharmacol.

177

125

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“…Overrepresented annotations from the two clusters, on top of those previously cited, included kinase, EGFR tyrosine kinase inhibitor resistance , and Serine/threonine-protein kinase . Several of these annotations have also been discussed in schizophrenia studies 42–44 , suggesting that other mechanisms might be at play. Figure 5a summarizes the annotation mapped to the two clusters along potential evidence for association with schizophrenia and ADHD extracted from a quantitative literature search.…”

Section: Resultsmentioning

confidence: 95%

Linking the genetic structure of neuroanatomical phenotypes with psychiatric disorders

Auvergne,

Traut,

Henches

et al. 2023

Preprint

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There is increasing evidence of shared genetic factors between psychiatric disorders and brain magnetic resonance imaging (MRI) phenotypes. However, deciphering the joint genetic architecture of these outcomes has proven challenging, and new approaches are needed to infer potential genetic structure underlying those phenotypes. Here, we demonstrate how multivariate analyses can help reveal links between MRI phenotypes and psychiatric disorders missed by univariate approaches. We first conducted univariate and multivariate genome-wide association studies (GWAS) for eight MRI-derived brain volume phenotypes in 20K UK Biobank participants. We performed various enrichment analyses to assess whether and how univariate and multitrait approaches can distinguish disorder-associated and non-disorder-associated variants from six psychiatric disorders: bipolarity, attention-deficit/hyperactivity disorder (ADHD), autism, schizophrenia, obsessive-compulsive disorder, and major depressive disorder. Univariate MRI GWAS displayed only negligible genetic correlation with psychiatric disorders at all the levels we investigated. Multitrait GWAS identified multiple new associations and showed significant enrichment for variants related to both ADHD and schizophrenia. We further clustered top associated variants based on their MRI multitrait association using an optimizedk-medoids approach and detected two clusters displaying not only enrichment for association with ADHD and schizophrenia, but also consistent direction of effects. Functional annotation analyses pointed to multiple potential mechanisms, suggesting in particular a role of neurotrophin pathways on both MRI and schizophrenia. Altogether our results show that multitrait association signature can be used to infer genetically-driven latent MRI variables associated with psychiatric disorders, opening paths for future biomarker development.

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“…There are different dopamine receptor subtypes, pharmacologically grouped as DRD1- (DRD1 and DRD5) and DRD2-like (DRD2S, DRD2L, DRD3, and DRD4) [ 44 ]. DRD2-like receptors are the main targets of antipsychotics [ 45 ]. The DRD2 has two isoforms: D2S and D2L, which differ because of a 29-amino-acid insertion in the third loop on D2L [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

GPCR Pharmacological Profiling of Aaptamine from the Philippine Sponge Stylissa sp. Extends Its Therapeutic Potential for Noncommunicable Diseases

Luyao

Luesch

2021

Molecules

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We report the first isolation of the alkaloid aaptamine from the Philippine marine sponge Stylissa sp. Aaptamine possessed weak antiproliferative activity against HCT116 colon cancer cells and inhibited the proteasome in vitro at 50 µM. These activities may be functionally linked. Due to its known, more potent activity on certain G-protein coupled receptors (GPCRs), including α-adrenergic and δ-opioid receptors, the compound was profiled more broadly at sub-growth inhibitory concentrations against a panel of 168 GPCRs to potentially reveal additional targets and therapeutic opportunities. GPCRs represent the largest class of drug targets. The primary screen at 20 µM using the β-arrestin functional assay identified the antagonist, agonist, and potentiators of agonist activity of aaptamine. Dose-response analysis validated the α-adrenoreceptor antagonist activity of aaptamine (ADRA2C, IC50 11.9 µM) and revealed the even more potent antagonism of the β-adrenoreceptor (ADRB2, IC50 0.20 µM) and dopamine receptor D4 (DRD4, IC50 6.9 µM). Additionally, aaptamine showed agonist activity on selected chemokine receptors, by itself (CXCR7, EC50 6.2 µM; CCR1, EC50 11.8 µM) or as a potentiator of agonist activity (CXCR3, EC50 31.8 µM; CCR3, EC50 16.2 µM). These GPCRs play a critical role in the treatment of cardiovascular disease, diabetes, cancer, and neurological disorders. The results of this study may thus provide novel preventive and therapeutic strategies for noncommunicable diseases (NCDs).

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Serum Epidermal Growth Factor is Low in Schizophrenia and Not Affected by Antipsychotics Alone or Combined With Electroconvulsive Therapy

Cited by 9 publications

References 30 publications

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Linking the genetic structure of neuroanatomical phenotypes with psychiatric disorders

GPCR Pharmacological Profiling of Aaptamine from the Philippine Sponge Stylissa sp. Extends Its Therapeutic Potential for Noncommunicable Diseases

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