RIC3, the cholinergic anti-inflammatory pathway, and neuroinflammation

Ben-David, Yael; Kagan, Sara; Ben-Ami, Hagit Cohen; Rostami, Jinar; Mizrahi, Tehila; Kulkarni, Abhijit; Thakur, Ganesh A.; Vaknin‐Dembinsky, Adi; Healy, Luke M.; Brenner, Talma; Treinin, Millet

doi:10.1016/j.intimp.2020.106381

Cited by 14 publications

(14 citation statements)

References 35 publications

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“…Moreover, increased average expression of RIC3 and CHRNA7 in lymphocytes from MS patients but not in healthy donors was observed. These data are consistent with a role for RIC3 and in its regulated expression in inflammatory processes and in neuroinflammatory diseases [45].…”

Section: Genetic Polymorphisms For Bche and Ache And Mssupporting

confidence: 88%

“…MS is believed to be dependent on multiple independent or interacting polymorphism genes with small or moderate effects, as well as their interaction with behavioral and environmental factors ( Figure 2) [43]. Several studies also aim to disclose the genetic basis of MS. For decades, only several variants of the HLA antigen were known to have the strongest effect on the risk of MS [44,45]. Carrying HLA-DRB1*1501 is associated with about three-fold greater odds of developing MS, while carrying HLA-A*02 is associated with meaningfully reduced odds.…”

Section: Genetic Polymorphisms For Bche and Ache And Msmentioning

confidence: 99%

“…All these variants only account for 20% to 30% of MS heritability, suggesting that its remaining part is likely related to epigenetic factors and gene-gene or gene-environment interactions. Considerable attention has been focused on studies evaluating disease-modifying effects in MS that identified genes such as the APOE, CXCR5, IL2RA, IL7R, IL7, IL12RB1, IL22RA2, IL12A, IL12B, IRF8, TNFRSF1A, TNFRSF14, TNFSF14, CBLB, GPR65, MALT1, RGS1, RIC3, STAT3, TAGAP, TYK2, CYP27B1 and CYP24A1 [44,45].…”

Section: Genetic Polymorphisms For Bche and Ache And Msmentioning

confidence: 99%

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Possible Correlation between Cholinergic System Alterations and Neuro/Inflammation in Multiple Sclerosis

et al. 2020

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Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system. Although the etiology of MS is still unknown, both genetic and environmental factors contribute to the pathogenesis of the disease. Acetylcholine participates in the modulation of central and peripheral inflammation. The cells of the immune system, as well as microglia, astrocytes and oligodendrocytes express cholinergic markers and receptors of muscarinic and nicotinic type. The role played by acetylcholine in MS has been recently investigated. In the present review, we summarize the evidence indicating the cholinergic dysfunction in serum and cerebrospinal fluid of relapsing–remitting (RR)-MS patients and in the brains of the MS animal model experimental autoimmune encephalomyelitis (EAE). The correlation between the increased activity of the cholinergic hydrolyzing enzymes acetylcholinesterase and butyrylcholinesterase, the reduced levels of acetylcholine and the increase of pro-inflammatory cytokines production were recently described in immune cells of MS patients. Moreover, the genetic polymorphisms for both hydrolyzing enzymes and the possible correlation with the altered levels of their enzymatic activity have been also reported. Finally, the changes in cholinergic markers expression in the central nervous system of EAE mice in peak and chronic phases suggest the involvement of the acetylcholine also in neuro-inflammatory processes.

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Section: Genetic Polymorphisms For Bche and Ache And Mssupporting

confidence: 88%

Section: Genetic Polymorphisms For Bche and Ache And Msmentioning

confidence: 99%

Section: Genetic Polymorphisms For Bche and Ache And Msmentioning

confidence: 99%

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Possible Correlation between Cholinergic System Alterations and Neuro/Inflammation in Multiple Sclerosis

et al. 2020

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“…Expression of RIC3 is dynamically regulated following immune activation and expression of both RIC3 and of the α7 nAChR encoding gene is significantly increased in immune cells from some MS patients, suggesting a role for RIC3 in inflammatory processes. Moreover, knockdown of RIC3 eliminated the anti‐inflammatory effects of cholinergic agonists on a macrophage cell line (Ben‐David et al., 2020). The α7 nAChR is known to mediate the anti‐inflammatory effects of cholinergic agonists as part of the cholinergic anti‐inflammatory pathway (Wang et al, 2003).…”

Section: Many Proteins Are Needed To Make Acetylcholine Receptorsmentioning

confidence: 99%

Cholinergic transmission in C. elegans: Functions, diversity, and maturation of ACh‐activated ion channels

Treinin¹,

Jin

2020

Journal of Neurochemistry

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Acetylcholine is an abundant neurotransmitter in all animals. Effects of acetylcholine are excitatory, inhibitory, or modulatory depending on the receptor and cell type. Research using the nematode C. elegans has made ground‐breaking contributions to the mechanistic understanding of cholinergic transmission. Powerful genetic screens for behavioral mutants or for responses to pharmacological reagents identified the core cellular machinery for synaptic transmission. Pharmacological reagents that perturb acetylcholine‐mediated processes led to the discovery and also uncovered the composition and regulators of acetylcholine‐activated channels and receptors. From a combination of electrophysiological and molecular cellular studies, we have gained a profound understanding of cholinergic signaling at the levels of synapses, neural circuits, and animal behaviors. This review will begin with a historical overview, then cover in‐depth current knowledge on acetylcholine‐activated ionotropic receptors, mechanisms regulating their functional expression and their functions in regulating locomotion.

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“…It could encode a member of the resistance to inhibitors of the cholinesterase 3‐like family, which may have functions including inflammation control. In human lymphocytes and macrophages, immune activation could lead to dynamic changes in RIC3 expression and RIC3 was found to show a strong correction with inflammatory processes [ 32 ]. In another study, RIC3‐TCRBC2 fusion was identified by RNA‐Seq in T‐cell lymphoblastic lymphoma, which might be a strong driver for neoplasia‐associated mutations [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic biomarker identification and tumor classification in breast cancer patients by methylation and transcriptome analysis

Zhong

2021

FEBS Open Bio

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Breast cancer (BC) is one of the most common and heterogeneous malignancies. Although prognosis of breast cancer has improved with the development of early screening, the mechanisms underlying tumorigenesis and progression remain incompletely understood. DNA methylation has been implicated in tumorigenesis and tumor development, and so here we screened methylation-driven genes and explored their prognostic values in breast cancer. RNA-Seq transcriptome data and DNA methylation data of the TCGA-BRCA dataset were obtained from The Cancer Genome Atlas. Differentially-expressed genes and differentially-methylated genes were identified separately. The intersected 783 samples with both RNA-Seq data and DNA methylation data were selected for further analysis. Fifty-six methylation-driven genes were identified using the MethylMix R package and ten prognosis methylation-driven genes (CDO1, CELF2, ITPAIPL1, KCNH8, PTK6, RAB25, RIC3, USP44, ZSCAN1, and ZSCAN23) were further screened by combined methylation and gene expression analysis. Based on the methylation data of the screened ten methylation-driven genes, six subgroups were identified with the ConsensusClusterPlus R package. The protein levels of the ten prognostic methylation-driven genes were detected by immunohistochemical experiments. Moreover, based on the RNA-Seq data, a signature calculating the risk score of each patient was developed with stepwise regression. The risk score and other clinical features (age and stage) were confirmed to be independent prognostic factors by univariate and multivariate Cox regression analyses. Finally, a prognostic nomogram incorporating all the significant factors was integrated to predict the 3-, 5-, and 7-year overall survival. Taken together, the methylation-driven genes identified here may be potential biomarkers of breast cancer.

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RIC3, the cholinergic anti-inflammatory pathway, and neuroinflammation

Cited by 14 publications

References 35 publications

Possible Correlation between Cholinergic System Alterations and Neuro/Inflammation in Multiple Sclerosis

Possible Correlation between Cholinergic System Alterations and Neuro/Inflammation in Multiple Sclerosis

Cholinergic transmission in C. elegans: Functions, diversity, and maturation of ACh‐activated ion channels

Prognostic biomarker identification and tumor classification in breast cancer patients by methylation and transcriptome analysis

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