Activating α7 nicotinic acetylcholine receptor inhibits <scp>NLRP</scp>3 inflammasome through regulation of β‐arrestin‐1

Peng, Ke; Shao, Bo-Zong; Xu, Zuojun; Chen, Xiongwen; Wei, Wei; Liu, Chong

doi:10.1111/cns.12758

Cited by 46 publications

(34 citation statements)

References 44 publications

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“…We found that the administration of cannabinoid receptor 2 (CB2R) agonist HU-308 significantly suppressed the activation of the NLRP3 inflammasome in microglia through the induction of autophagy process, thus producing an ameliorative effect on EAE ( Shao et al, 2014 ). Furthermore, it was also reported by us that the activation of α7 nicotinic acetylcholine receptor (α7nAChR) by PNU282987 largely suppressed the NLRP3 inflammasome in monocyte/macrophage system in EAE, thus leading to the alleviation of the severity of EAE ( Ke et al, 2017 ). Those effects were mainly through the downregulation of the interaction between the NLRP3 protein and β-arrestin-1 in microglia ( Ke et al, 2017 ).…”

Section: Nlrp3 Inflammasome In Cns Disordersmentioning

confidence: 92%

“…Furthermore, it was also reported by us that the activation of α7 nicotinic acetylcholine receptor (α7nAChR) by PNU282987 largely suppressed the NLRP3 inflammasome in monocyte/macrophage system in EAE, thus leading to the alleviation of the severity of EAE ( Ke et al, 2017 ). Those effects were mainly through the downregulation of the interaction between the NLRP3 protein and β-arrestin-1 in microglia ( Ke et al, 2017 ).…”

Section: Nlrp3 Inflammasome In Cns Disordersmentioning

confidence: 92%

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Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases

Shao

Cao

2018

Front. Mol. Neurosci.

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Central nervous system (CNS) is one of the largest killers of people’s health all over the world. The overactivation of the immune and inflammatory responses is considered as an important factor, contributing to the pathogenesis and progression of CNS disorders. Among all kinds of immune and inflammatory reaction, the inflammasome, a complex of proteins, has been drawn increasingly attention to by researchers. The initiation and activation of the inflammasome is involved in the onset of various kinds of diseases. The NLRP3 inflammasome, the most studied member of the inflammasome, is closely associated with many kinds of CNS disorders. Here in this review, the roles of the NLRP3 inflammasome in the pathogenesis and progression of several well-known CNS diseases would be discussed, including cerebrovascular diseases, neurodegenerative diseases, multiple sclerosis, depression as well as other CNS disorders. In addition, several therapeutic strategies targeting on the NLRP3 inflammasome for the treatment of CNS disorders would be described in this review.

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Section: Nlrp3 Inflammasome In Cns Disordersmentioning

confidence: 92%

Section: Nlrp3 Inflammasome In Cns Disordersmentioning

confidence: 92%

Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases

Shao

Cao

2018

Front. Mol. Neurosci.

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“…Western blot analysis of ARRB2 (A), NOD2 (C) and TRAF6 (D) protein levels in the penumbral cortex from WT mice after 2 h occlusion of the middle cerebral artery (MCAO) and 2, 6, 12, 24, 48 and 72 h reperfusion. 13 However, specific molecular mechanism involved in the regulation of ARRB2 in NOD2-induced inflammation in cerebral I/R injury remains poorly understood. *P < 0.05 compared with sham group.…”

Section: Introductionmentioning

confidence: 99%

“…11 Moreover, ARRB2 plays a prominent role in the negative regulation of TLR4-triggered inflammatory responses by regulating p38 MAPK function 12 and ARRB2 interacted with NLRP3 to inhibit inflammation after traumatic brain injury. 13 However, specific molecular mechanism involved in the regulation of ARRB2 in NOD2-induced inflammation in cerebral I/R injury remains poorly understood. Here, we demonstrated that ARRB2 negatively regulated NOD2 signalling pathway through the association with TRAF6 in microglia after cerebral I/R injury.…”

Section: Introductionmentioning

confidence: 99%

β‐arrestin 2 negatively regulates NOD2 signalling pathway through association with TRAF6 in microglia after cerebral ischaemia/reperfusion injury

Chen

Kong

Wei

et al. 2019

J Cellular Molecular Medi

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We previously reported that nucleotide‐binding oligomerization domain‐containing protein ( NOD ) 2 was involved in the inflammatory responses to cerebral ischaemia/reperfusion (I/R) insult. However, the mechanism by which NOD 2 participates in brain ischaemic injury and the regulation of NOD 2 in the process are still obscure. Increased β‐arrestin 2 ( ARRB 2) expression was observed in microglia following cerebral I/R in wild‐type mice besides the up‐regulation of NOD 2 and TRAF 6. Stimulation of NOD 2 by muramyl dipeptide ( MDP ) in BV 2 cells induced the activation of NF ‐κB by the phosphorylation of p65 subunit and the degradation of IκBα. Meanwhile, the protein level of Cyclooxygenase‐2 (COX‐2), the protein expression and activity of MMP ‐9 were significantly increased in BV 2 cells after administration of MDP . Furthermore, overexpression of ARRB 2 significantly suppressed the inflammation induced by MDP , silence of ARRB 2 significantly enhanced the inflammation induced by MDP in BV 2 cells. In addition, we observed endogenous interaction of TRAF 6 and ARRB 2 after stimulation of MDP or cerebral I/R insult, indicating ARRB 2 negatively regulates NOD 2‐triggered inflammatory signalling pathway by associating with TRAF 6 in microglia after cerebral I/R injury. Finally, the in vivo study clearly confirmed that ARRB 2 negatively regulated NOD 2‐induced inflammatory response, as ARRB 2 deficiency exacerbated stroke outcomes and aggravated the NF ‐κB signalling pathway induced by NOD 2 stimulation after cerebral I/R injury. These findings revealed ARRB 2 negatively regulated NOD 2 signalling pathway through the association with TRAF 6 in cerebral I/R injury.

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“…Interestingly the upregulated expression of M3 receptor subtype in these cells causes an increase of MHC-I and MHC-II expression, suggesting the pro-inflammatory microglia phenotype [83]. Microglia also display nicotinic receptors, with a prevalence of a7 subunit [84][85][86][87]. For these reasons, this nicotinic receptor subtype may be considered an interesting therapeutic target for several neurological disorders considering its ability to modulate the cholinergic anti-inflammatory pathway and the synaptic plasticity.…”

Section: Cholinergic Receptors In the Glial Cellsmentioning

confidence: 99%

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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Activating α7 nicotinic acetylcholine receptor inhibits NLRP3 inflammasome through regulation of β‐arrestin‐1

Abstract: The present study demonstrates that activating α7nAChR can lead to NLRP3 inflammasome inhibition via regulation of β-arrestin-1 in monocyte/microglia system.

Cited by 46 publications

References 44 publications

Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases

Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases

β‐arrestin 2 negatively regulates NOD2 signalling pathway through association with TRAF6 in microglia after cerebral ischaemia/reperfusion injury

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

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