P2X7R介导的神经炎症在神经精神疾病中的作用
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摘要
嘌呤能P2X7受体(P2X7R)是腺苷三磷酸门控阳离子通道受体,作为嘌呤受体P2X家族受体亚型之一,主要由各种免疫细胞表达。P2X7R及其介导的信号通路可触发炎症反应的激活,具有介导先天免疫反应的重要作用。中枢神经系统的炎症反应能激活小胶质细胞,从而导致白细胞介素1β等炎性因子的释放,这些炎性因子促使组织变性、损伤及细胞的死亡。目前认为,神经炎症是神经退行性疾病、精神疾病和各种脑损伤的病理进程中的重要一环,也就成为人们试图干预这些疾病落脚点。
The P2X7 receptor( P2X7 R) is an adenosine triphosphate-gated cation channel receptor,which is one of the subtypes of the purinergic P2X receptor family,and is mainly expressed by various immune cells. P2X7 R and its mediated signaling pathway trigger the activation of inflammatory responses and have an important role in mediating innate immune responses. The inflammatory response of the central nervous system activates microglia,which leads to the release of inflammatory factors such as interleukin-1β,promoting tissue degeneration,damage and cell death. It is currently believed that neuroinflammation is an important part of the pathological process of neurodegenerative diseases,mental diseases and various brain injuries,and it has become a target in the attempt to intervene in these diseases.
The P2X7 receptor( P2X7 R) is an adenosine triphosphate-gated cation channel receptor,which is one of the subtypes of the purinergic P2X receptor family,and is mainly expressed by various immune cells. P2X7 R and its mediated signaling pathway trigger the activation of inflammatory responses and have an important role in mediating innate immune responses. The inflammatory response of the central nervous system activates microglia,which leads to the release of inflammatory factors such as interleukin-1β,promoting tissue degeneration,damage and cell death. It is currently believed that neuroinflammation is an important part of the pathological process of neurodegenerative diseases,mental diseases and various brain injuries,and it has become a target in the attempt to intervene in these diseases.
引文
[1]Northoff G,Stanghellini G.How to Link Brain and Experience?Spatiotemporal Psychopathology of the Lived Body[J].Front Hum Neurosci,2016,10:76.
[2]Radtke FA,Chapman G,Hall J,et al.Modulating Neuroinflammation to Treat Neuropsychiatric Disorders[J].Biomed Res Int,2017,2017:5071786.
[3]Jones KA,Thomsen C.The role of the innate immune system in psychiatric disorders[J].Mol Cell Neurosci,2013,53(3):52-62.
[4]Réus GZ,Fries GR,Stertz L,et al.The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders[J].Neurosci,2015,300:141-154.
[5]Bhattacharya A,Derecki NC,Lovenberg TW,et al.Role of neuroimmunological factors in the pathophysiology of mood disorders[J].Curr Top Behav Neurosci,2016,233(9):1623-1636.
[6]Bhattacharya A,Biber K.The microglial ATP-gated ion channel P2X7 as a CNS drug target[J].Glia,2016,64(10):1772-1787.
[7]Giuliani AL,Sarti AC,Falzoni S,et al.The P2X7 Receptor-Interleukin-1 Liaison[J].Front Pharmacol,2017,8(524):123.
[8]Chrovian CC,Rech JC,Bhattacharya A,et al.P2X7 Antagonists as Potential Therapeutic Agents for the Treatment of CNS Disorders[J].Prog Med Chem,2014,53(53):65-100.
[9]Pippel A,Stolz M,Woltersdorf R,et al.Localization of the gate and selectivity filter of the full-length P2X7 receptor[J].Proc Natl Acad Sci U S A,2017,114(11):E2156.
[10]Burnstock G.P2X ion channel receptors and inflammation[J].Purinergic Signal,2016,12(1):59-67.
[11]Chen Z,He L,Li L,et al.The P2X7 purinergic receptor:An emerging therapeutic target in cardiovascular diseases[J].Clin Chim Acta,2018,479:196-207.
[12]Wei L,Mortadza S,Yan J,et al.ATP-activated P2X7 receptor in the pathophysiology of mood disorders and as an emerging target for the development of novel antidepressant therapeutics[J].Neurosci Biobehav Rev,2018,87:192-205.
[13]Bartlett R,Stokes L,Sluyter R.The P2X7 Receptor Channel:Recent Developments and the Use of P2X7 Antagonists in Models of Disease[J].Pharmacol Rev,2014,66(3):638.
[14]Virgilio FD,Giuliani AL,Vultaggio-Poma V,et al.Non-nucleotide Agonists Triggering P2X7 Receptor Activation and Pore Formation[J].Front Pharmacol,2018,9:39.
[15]Beamer E,G9l9ncsér F,Horváth G,et al.Purinergic mechanisms in neuroinflammation:An update from molecules to behavior[J].Neuropharmacology,2016,104:94-104.
[16]He Y,Taylor N,Fourgeaud L,et al.The role of microglial P2X7:Modulation of cell death and cytokine release[J].J Neuroinflammation,2017,14(1):135.
[17]Di VF,Dal BD,Sarti AC,et al.The P2X7 Receptor in Infection and Inflammation[J].Immunity,2017,47(1):15.
[18]Mu1oz-Planillo R,Kuffa P,Martínez-Colón G,et al.K+,Efflux Is the Common Trigger of NLRP3 Inflammasome Activation by Bacterial Toxins and Particulate Matter[J].Immunity,2013,38(6):1142-1153.
[19]Ferrari D,Pizzirani CE,Lemoli RM,et al.The P2X7 receptor:Akey player in IL-1 processing and release[J].J Immunol,2006,176(7):3877-3883.
[20]Karmakar M,Katsnelson MA,Dubyak GR,et al.Neutrophil P2X7receptors mediate NLRP3 inflammasome-dependent IL-1βsecretion in response to ATP[J].Nat Commun,2016,7:10555.
[21]Burnstock G,Boeynaems JM.Purinergic signalling and immune cells[J].Purinergic Signal,2014,10(4):529-564.
[22]Stokes L,Spencer SJ,Jenkins TA.Understanding the role of P2X7in affective disorders-are glial cells the major players[J].Front Cell Neurosci,2015,9:258.
[23]Fiebich BL,Akter S,Akundi RS.The two-hit hypothesis for neuroinflammation:Role of exogenous ATP in modulating inflammation in the brain[J].Front Cell Neurosci,2014,8(8):260.
[24]张紫萱,田绍文,游咏.神经炎症在神经退行性疾病和精神疾病中的病理生理作用[J].中南医学科学杂志,2017,45(3):312-314.
[25]Burnstock G.Introduction to purinergic signalling in the brain[J].Adv Exp Med Biol,2013,986:1-12.
[26]Burnstock G,Knight GE.The potential of P2X7 receptors as a therapeutic target,including inflammation and tumour progression[J].Purinergic Signal,2017,14(1):1-18.
[27]Pfau ML,Russo SJ.Neuroinflammation regulates cognitive impairment in socially defeated mice[J].Trends Neurosci,2016,39(6):353-355.
[28]Cisnerosmejorado A,Pérezsamartín A,Gottlieb M,et al.ATP signaling in brain:Release,excitotoxicity and potential therapeutic targets[J].Cell Mol Neurobiol,2015,35(1):1-6.
[29]Koványi B,Cs9lle C,Calovi S,et al.The role of P2X7 receptors in a rodent PCP-induced schizophrenia model[J].Sci Rep,2016,6:36680.
[30]Laskaris LE,Di BM,Everall I,et al.Microglial activation and progressive brain changes in schizophrenia[J].Br J Pharmacol,2016,173(4):666-680.
[31]Tan S,Wang Y,Chen K,et al.Ketamine Alleviates DepressiveLike Behaviors via Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice[J].Biol Pharm Bull,2017,40(8):1260-1267.
[32]Zhang K,Liu J,You X,et al.P2X7 as a new target for chrysophanol to treat lipopolysaccharide-induced depression in mice[J].Neurosci Lett,2016,613:60-65.
[33]Rassendren F,Audinat E.Purinergic signaling in epilepsy[J].J Neurosci Res,2016,94(9):781-793.
[34]Beamer E,Fischer W,Engel T.The ATP-Gated P2X7 Receptor As a Target for the Treatment of Drug-Resistant Epilepsy[J].Front Neurosci,2017,11:21.
[35]Cie lak M,Wojtczak A,Komoszyński M.Role of the purinergic signaling in epilepsy[J].Pharmacol Rep,2017,69(1):130-138.
[36]Rodriguez-Alvarez N,Jimenez-Mateos EM,Engel T,et al.Effects of P2X7 receptor antagonists on hypoxia-induced neonatal seizures in mice[J].Neuropharmacology,2017,116:351-363.
[37]Jorg M,Scammells PJ,Capuano B.The Dopamine D2 and Adenosine A2A Receptors:Past,Present and Future Trends for the Treatment of Parkinson's Disease[J].Curr Med Chem,2014,21(27):3188-3210.
[38]Wang XH,Xie X,Luo XG,et al.Inhibiting purinergic P2X7receptors with the antagonist brilliant blue G is neuroprotective in an intranigral lipopolysaccharide animal model of Parkinson's disease[J].Mol Med Rep,2017,15(2):768-776.
[39]Wilkaniec A,Gssowska M,Czapski GA,et al.P2X7 receptorpannexin 1 interaction mediates extracellular alpha-synucleininduced ATP release in neuroblastoma SH-SY5Y cells[J].Purinergic Signal,2017,13(3):1-15.
[40]Jiang T,Hoekstra J,Heng X,et al.P2X7 receptor is critical inα-synuclein-mediated microglial NADPH oxidase activation[J].Neurobiol Aging,2015,36(7):2304-2318.
[41]Hoang QQ.Pathway for Parkinson disease[J].Proc Natl Acad Sci U S A,2014,111(7):2402-2403.
[42]Ross CA,Tabrizi SJ.Huntington's disease:From molecular pathogenesis to clinical treatment[J].Lancet Neurol,2011,10(1):83-98.
[43]Zheng Z,Diamond MI.Huntington disease and the huntingtin protein[J].Prog Mol Biol Transl Sci,2012,107:189-214.
[44]Luo C,Jian C,Liao Y,et al.The role of microglia in multiple sclerosis[J].Neuropsych Dis Treat,2017,13:1661-1667.
[45]Gu BJ,Field J,Dutertre S,et al.A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis[J].Hum Mol Genet,2015,24(19):5644-5654.
[46]Yiangou Y,Facer P,Durrenberger P,et al.COX-2,CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord[J].BMC Neurology,2006,6(1):12.
[47]Dendrou CA,Fugger L,Friese MA.Immunopathology of multiple sclerosis[J].Nat Rev Immunol,2015,15(9):545-558.
[2]Radtke FA,Chapman G,Hall J,et al.Modulating Neuroinflammation to Treat Neuropsychiatric Disorders[J].Biomed Res Int,2017,2017:5071786.
[3]Jones KA,Thomsen C.The role of the innate immune system in psychiatric disorders[J].Mol Cell Neurosci,2013,53(3):52-62.
[4]Réus GZ,Fries GR,Stertz L,et al.The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders[J].Neurosci,2015,300:141-154.
[5]Bhattacharya A,Derecki NC,Lovenberg TW,et al.Role of neuroimmunological factors in the pathophysiology of mood disorders[J].Curr Top Behav Neurosci,2016,233(9):1623-1636.
[6]Bhattacharya A,Biber K.The microglial ATP-gated ion channel P2X7 as a CNS drug target[J].Glia,2016,64(10):1772-1787.
[7]Giuliani AL,Sarti AC,Falzoni S,et al.The P2X7 Receptor-Interleukin-1 Liaison[J].Front Pharmacol,2017,8(524):123.
[8]Chrovian CC,Rech JC,Bhattacharya A,et al.P2X7 Antagonists as Potential Therapeutic Agents for the Treatment of CNS Disorders[J].Prog Med Chem,2014,53(53):65-100.
[9]Pippel A,Stolz M,Woltersdorf R,et al.Localization of the gate and selectivity filter of the full-length P2X7 receptor[J].Proc Natl Acad Sci U S A,2017,114(11):E2156.
[10]Burnstock G.P2X ion channel receptors and inflammation[J].Purinergic Signal,2016,12(1):59-67.
[11]Chen Z,He L,Li L,et al.The P2X7 purinergic receptor:An emerging therapeutic target in cardiovascular diseases[J].Clin Chim Acta,2018,479:196-207.
[12]Wei L,Mortadza S,Yan J,et al.ATP-activated P2X7 receptor in the pathophysiology of mood disorders and as an emerging target for the development of novel antidepressant therapeutics[J].Neurosci Biobehav Rev,2018,87:192-205.
[13]Bartlett R,Stokes L,Sluyter R.The P2X7 Receptor Channel:Recent Developments and the Use of P2X7 Antagonists in Models of Disease[J].Pharmacol Rev,2014,66(3):638.
[14]Virgilio FD,Giuliani AL,Vultaggio-Poma V,et al.Non-nucleotide Agonists Triggering P2X7 Receptor Activation and Pore Formation[J].Front Pharmacol,2018,9:39.
[15]Beamer E,G9l9ncsér F,Horváth G,et al.Purinergic mechanisms in neuroinflammation:An update from molecules to behavior[J].Neuropharmacology,2016,104:94-104.
[16]He Y,Taylor N,Fourgeaud L,et al.The role of microglial P2X7:Modulation of cell death and cytokine release[J].J Neuroinflammation,2017,14(1):135.
[17]Di VF,Dal BD,Sarti AC,et al.The P2X7 Receptor in Infection and Inflammation[J].Immunity,2017,47(1):15.
[18]Mu1oz-Planillo R,Kuffa P,Martínez-Colón G,et al.K+,Efflux Is the Common Trigger of NLRP3 Inflammasome Activation by Bacterial Toxins and Particulate Matter[J].Immunity,2013,38(6):1142-1153.
[19]Ferrari D,Pizzirani CE,Lemoli RM,et al.The P2X7 receptor:Akey player in IL-1 processing and release[J].J Immunol,2006,176(7):3877-3883.
[20]Karmakar M,Katsnelson MA,Dubyak GR,et al.Neutrophil P2X7receptors mediate NLRP3 inflammasome-dependent IL-1βsecretion in response to ATP[J].Nat Commun,2016,7:10555.
[21]Burnstock G,Boeynaems JM.Purinergic signalling and immune cells[J].Purinergic Signal,2014,10(4):529-564.
[22]Stokes L,Spencer SJ,Jenkins TA.Understanding the role of P2X7in affective disorders-are glial cells the major players[J].Front Cell Neurosci,2015,9:258.
[23]Fiebich BL,Akter S,Akundi RS.The two-hit hypothesis for neuroinflammation:Role of exogenous ATP in modulating inflammation in the brain[J].Front Cell Neurosci,2014,8(8):260.
[24]张紫萱,田绍文,游咏.神经炎症在神经退行性疾病和精神疾病中的病理生理作用[J].中南医学科学杂志,2017,45(3):312-314.
[25]Burnstock G.Introduction to purinergic signalling in the brain[J].Adv Exp Med Biol,2013,986:1-12.
[26]Burnstock G,Knight GE.The potential of P2X7 receptors as a therapeutic target,including inflammation and tumour progression[J].Purinergic Signal,2017,14(1):1-18.
[27]Pfau ML,Russo SJ.Neuroinflammation regulates cognitive impairment in socially defeated mice[J].Trends Neurosci,2016,39(6):353-355.
[28]Cisnerosmejorado A,Pérezsamartín A,Gottlieb M,et al.ATP signaling in brain:Release,excitotoxicity and potential therapeutic targets[J].Cell Mol Neurobiol,2015,35(1):1-6.
[29]Koványi B,Cs9lle C,Calovi S,et al.The role of P2X7 receptors in a rodent PCP-induced schizophrenia model[J].Sci Rep,2016,6:36680.
[30]Laskaris LE,Di BM,Everall I,et al.Microglial activation and progressive brain changes in schizophrenia[J].Br J Pharmacol,2016,173(4):666-680.
[31]Tan S,Wang Y,Chen K,et al.Ketamine Alleviates DepressiveLike Behaviors via Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice[J].Biol Pharm Bull,2017,40(8):1260-1267.
[32]Zhang K,Liu J,You X,et al.P2X7 as a new target for chrysophanol to treat lipopolysaccharide-induced depression in mice[J].Neurosci Lett,2016,613:60-65.
[33]Rassendren F,Audinat E.Purinergic signaling in epilepsy[J].J Neurosci Res,2016,94(9):781-793.
[34]Beamer E,Fischer W,Engel T.The ATP-Gated P2X7 Receptor As a Target for the Treatment of Drug-Resistant Epilepsy[J].Front Neurosci,2017,11:21.
[35]Cie lak M,Wojtczak A,Komoszyński M.Role of the purinergic signaling in epilepsy[J].Pharmacol Rep,2017,69(1):130-138.
[36]Rodriguez-Alvarez N,Jimenez-Mateos EM,Engel T,et al.Effects of P2X7 receptor antagonists on hypoxia-induced neonatal seizures in mice[J].Neuropharmacology,2017,116:351-363.
[37]Jorg M,Scammells PJ,Capuano B.The Dopamine D2 and Adenosine A2A Receptors:Past,Present and Future Trends for the Treatment of Parkinson's Disease[J].Curr Med Chem,2014,21(27):3188-3210.
[38]Wang XH,Xie X,Luo XG,et al.Inhibiting purinergic P2X7receptors with the antagonist brilliant blue G is neuroprotective in an intranigral lipopolysaccharide animal model of Parkinson's disease[J].Mol Med Rep,2017,15(2):768-776.
[39]Wilkaniec A,Gssowska M,Czapski GA,et al.P2X7 receptorpannexin 1 interaction mediates extracellular alpha-synucleininduced ATP release in neuroblastoma SH-SY5Y cells[J].Purinergic Signal,2017,13(3):1-15.
[40]Jiang T,Hoekstra J,Heng X,et al.P2X7 receptor is critical inα-synuclein-mediated microglial NADPH oxidase activation[J].Neurobiol Aging,2015,36(7):2304-2318.
[41]Hoang QQ.Pathway for Parkinson disease[J].Proc Natl Acad Sci U S A,2014,111(7):2402-2403.
[42]Ross CA,Tabrizi SJ.Huntington's disease:From molecular pathogenesis to clinical treatment[J].Lancet Neurol,2011,10(1):83-98.
[43]Zheng Z,Diamond MI.Huntington disease and the huntingtin protein[J].Prog Mol Biol Transl Sci,2012,107:189-214.
[44]Luo C,Jian C,Liao Y,et al.The role of microglia in multiple sclerosis[J].Neuropsych Dis Treat,2017,13:1661-1667.
[45]Gu BJ,Field J,Dutertre S,et al.A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis[J].Hum Mol Genet,2015,24(19):5644-5654.
[46]Yiangou Y,Facer P,Durrenberger P,et al.COX-2,CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord[J].BMC Neurology,2006,6(1):12.
[47]Dendrou CA,Fugger L,Friese MA.Immunopathology of multiple sclerosis[J].Nat Rev Immunol,2015,15(9):545-558.