Skip to main content
Top
Published in: Translational Neurodegeneration 1/2015

Open Access 01-12-2015 | Review

Neuroinflammation in Parkinson’s disease and its potential as therapeutic target

Authors: Qinqin Wang, Yingjun Liu, Jiawei Zhou

Published in: Translational Neurodegeneration | Issue 1/2015

Login to get access

Abstract

Parkinson’s disease (PD), the second most common age-associated neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons and the presence of α-synuclein-containing aggregates in the substantia nigra pars compacta (SNpc). Chronic neuroinflammation is one of the hallmarks of PD pathophysiology. Post-mortem analyses of human PD patients and experimental animal studies indicate that activation of glial cells and increases in pro-inflammatory factor levels are common features of the PD brain. Chronic release of pro-inflammatory cytokines by activated astrocytes and microglia leads to the exacerbation of DA neuron degeneration in the SNpc. Besides, peripheral immune system is also implicated in the pathogenesis of PD. Infiltration and accumulation of immune cells from the periphery are detected in and around the affected brain regions of PD patients. Moreover, inflammatory processes have been suggested as promising interventional targets for PD and even other neurodegenerative diseases. A better understanding of the role of inflammation in PD will provide new insights into the pathological processes and help to establish effective therapeutic strategies. In this review, we will summarize recent progresses in the neuroimmune aspects of PD and highlight the potential therapeutic interventions targeting neuroinflammation.
Literature
1.
go back to reference Fahn S. Description of Parkinson’s disease as a clinical syndrome. Ann N Y Acad Sci. 2003;991:1–14.PubMedCrossRef Fahn S. Description of Parkinson’s disease as a clinical syndrome. Ann N Y Acad Sci. 2003;991:1–14.PubMedCrossRef
2.
go back to reference von Campenhausen S, Bornschein B, Wick R, Botzel K, Sampaio C, Poewe W, et al. Prevalence and incidence of Parkinson’s disease in Europe. Eur Neuropsychopharmacol. 2005;15:473–90.CrossRef von Campenhausen S, Bornschein B, Wick R, Botzel K, Sampaio C, Poewe W, et al. Prevalence and incidence of Parkinson’s disease in Europe. Eur Neuropsychopharmacol. 2005;15:473–90.CrossRef
3.
go back to reference Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol. 2011;26 Suppl 1:S1–58.PubMedCrossRef Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol. 2011;26 Suppl 1:S1–58.PubMedCrossRef
4.
go back to reference Waak J, Weber SS, Waldenmaier A, Gorner K, Alunni-Fabbroni M, Schell H, et al. Regulation of astrocyte inflammatory responses by the Parkinson’s disease-associated gene DJ-1. FASEB J. 2009;23:2478–89.PubMedCrossRef Waak J, Weber SS, Waldenmaier A, Gorner K, Alunni-Fabbroni M, Schell H, et al. Regulation of astrocyte inflammatory responses by the Parkinson’s disease-associated gene DJ-1. FASEB J. 2009;23:2478–89.PubMedCrossRef
5.
go back to reference Mori F, Piao YS, Hayashi S, Fujiwara H, Hasegawa M, Yoshimoto M, et al. Alpha-synuclein accumulates in Purkinje cells in Lewy body disease but not in multiple system atrophy. J Neuropathol Exp Neurol. 2003;62:812–9.PubMed Mori F, Piao YS, Hayashi S, Fujiwara H, Hasegawa M, Yoshimoto M, et al. Alpha-synuclein accumulates in Purkinje cells in Lewy body disease but not in multiple system atrophy. J Neuropathol Exp Neurol. 2003;62:812–9.PubMed
6.
go back to reference Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29:1583–90.PubMedCrossRef Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29:1583–90.PubMedCrossRef
7.
8.
go back to reference Block ML, Hong JS. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol. 2005;76:77–98.PubMedCrossRef Block ML, Hong JS. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol. 2005;76:77–98.PubMedCrossRef
9.
go back to reference Hirsch EC, Vyas S, Hunot S. Neuroinflammation in Parkinson’s disease. Parkinsonism Relat Disord. 2012;18:S210–S2.PubMedCrossRef Hirsch EC, Vyas S, Hunot S. Neuroinflammation in Parkinson’s disease. Parkinsonism Relat Disord. 2012;18:S210–S2.PubMedCrossRef
10.
go back to reference Lv Y, Zhang Z, Hou L, Zhang L, Zhang J, Wang Y, et al. Phytic acid attenuates inflammatory responses and the levels of NF-kappaB and p-ERK in MPTP-induced Parkinson’s disease model of mice. Neurosci Lett. 2015;597:132–6.PubMedCrossRef Lv Y, Zhang Z, Hou L, Zhang L, Zhang J, Wang Y, et al. Phytic acid attenuates inflammatory responses and the levels of NF-kappaB and p-ERK in MPTP-induced Parkinson’s disease model of mice. Neurosci Lett. 2015;597:132–6.PubMedCrossRef
11.
go back to reference Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, et al. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell. 2009;137:47–59.PubMedCentralPubMedCrossRef Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, et al. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell. 2009;137:47–59.PubMedCentralPubMedCrossRef
12.
go back to reference McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology. 1988;38:1285–91.PubMedCrossRef McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology. 1988;38:1285–91.PubMedCrossRef
13.
go back to reference Bartels AL, Willemsen AT, Doorduin J, de Vries EF, Dierckx RA, Leenders KL. [11C]-PK11195 PET: quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson’s disease? Parkinsonism Relat Disord. 2010;16:57–9.PubMedCrossRef Bartels AL, Willemsen AT, Doorduin J, de Vries EF, Dierckx RA, Leenders KL. [11C]-PK11195 PET: quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson’s disease? Parkinsonism Relat Disord. 2010;16:57–9.PubMedCrossRef
14.
go back to reference Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis. 2006;21:404–12.PubMedCrossRef Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis. 2006;21:404–12.PubMedCrossRef
15.
go back to reference Leal MC, Casabona JC, Puntel M, Pitossi FJ. Interleukin-1beta and tumor necrosis factor-alpha: reliable targets for protective therapies in Parkinson’s Disease? Front Cell Neurosci. 2013;7:53.PubMedCentralPubMedCrossRef Leal MC, Casabona JC, Puntel M, Pitossi FJ. Interleukin-1beta and tumor necrosis factor-alpha: reliable targets for protective therapies in Parkinson’s Disease? Front Cell Neurosci. 2013;7:53.PubMedCentralPubMedCrossRef
16.
go back to reference Benner EJ, Banerjee R, Reynolds AD, Sherman S, Pisarev VM, Tsiperson V, et al. Nitrated alpha-synuclein immunity accelerates degeneration of nigral dopaminergic neurons. PLoS One. 2008;3:e1376.PubMedCentralPubMedCrossRef Benner EJ, Banerjee R, Reynolds AD, Sherman S, Pisarev VM, Tsiperson V, et al. Nitrated alpha-synuclein immunity accelerates degeneration of nigral dopaminergic neurons. PLoS One. 2008;3:e1376.PubMedCentralPubMedCrossRef
17.
go back to reference Tansey MG, McCoy MK, Frank-Cannon TC. Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol. 2007;208:1–25.PubMedCentralPubMedCrossRef Tansey MG, McCoy MK, Frank-Cannon TC. Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol. 2007;208:1–25.PubMedCentralPubMedCrossRef
19.
go back to reference Wright GJ, Puklavec MJ, Willis AC, Hoek RM, Sedgwick JD, Brown MH, et al. Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Immunity. 2000;13:233–42.PubMedCrossRef Wright GJ, Puklavec MJ, Willis AC, Hoek RM, Sedgwick JD, Brown MH, et al. Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Immunity. 2000;13:233–42.PubMedCrossRef
20.
go back to reference Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM, et al. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science. 2000;290:1768–71.PubMedCrossRef Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM, et al. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science. 2000;290:1768–71.PubMedCrossRef
21.
go back to reference Mott RT, Ait-Ghezala G, Town T, Mori T, Vendrame M, Zeng J, et al. Neuronal expression of CD22: novel mechanism for inhibiting microglial proinflammatory cytokine production. Glia. 2004;46:369–79.PubMedCrossRef Mott RT, Ait-Ghezala G, Town T, Mori T, Vendrame M, Zeng J, et al. Neuronal expression of CD22: novel mechanism for inhibiting microglial proinflammatory cytokine production. Glia. 2004;46:369–79.PubMedCrossRef
22.
go back to reference Numakawa T, Ishimoto T, Suzuki S, Numakawa Y, Adachi N, Matsumoto T, et al. Neuronal roles of the integrin-associated protein (IAP/CD47) in developing cortical neurons. J Biol Chem. 2004;279:43245–53.PubMedCrossRef Numakawa T, Ishimoto T, Suzuki S, Numakawa Y, Adachi N, Matsumoto T, et al. Neuronal roles of the integrin-associated protein (IAP/CD47) in developing cortical neurons. J Biol Chem. 2004;279:43245–53.PubMedCrossRef
23.
go back to reference Smith RE, Patel V, Seatter SD, Deehan MR, Brown MH, Brooke GP, et al. A novel MyD-1 (SIRP-1alpha) signaling pathway that inhibits LPS-induced TNFalpha production by monocytes. Blood. 2003;102:2532–40.PubMedCrossRef Smith RE, Patel V, Seatter SD, Deehan MR, Brown MH, Brooke GP, et al. A novel MyD-1 (SIRP-1alpha) signaling pathway that inhibits LPS-induced TNFalpha production by monocytes. Blood. 2003;102:2532–40.PubMedCrossRef
24.
go back to reference Chang RC, Hudson P, Wilson B, Liu B, Abel H, Hemperly J, et al. Immune modulatory effects of neural cell adhesion molecules on lipopolysaccharide-induced nitric oxide production by cultured glia. Brain Res Mol Brain Res. 2000;81:197–201.PubMedCrossRef Chang RC, Hudson P, Wilson B, Liu B, Abel H, Hemperly J, et al. Immune modulatory effects of neural cell adhesion molecules on lipopolysaccharide-induced nitric oxide production by cultured glia. Brain Res Mol Brain Res. 2000;81:197–201.PubMedCrossRef
25.
go back to reference Vernet-der Garabedian B, Derer P, Bailly Y, Mariani J. Innate immunity in the Grid2Lc/+ mouse model of cerebellar neurodegeneration: glial CD95/CD95L plays a non-apoptotic role in persistent neuron loss-associated inflammatory reactions in the cerebellum. J Neuroinflammation. 2013;10:65.PubMedCentralPubMedCrossRef Vernet-der Garabedian B, Derer P, Bailly Y, Mariani J. Innate immunity in the Grid2Lc/+ mouse model of cerebellar neurodegeneration: glial CD95/CD95L plays a non-apoptotic role in persistent neuron loss-associated inflammatory reactions in the cerebellum. J Neuroinflammation. 2013;10:65.PubMedCentralPubMedCrossRef
26.
go back to reference Chang RC, Hudson P, Wilson B, Haddon L, Hong JS. Influence of neurons on lipopolysaccharide-stimulated production of nitric oxide and tumor necrosis factor-alpha by cultured glia. Brain Res. 2000;853:236–44.PubMedCrossRef Chang RC, Hudson P, Wilson B, Haddon L, Hong JS. Influence of neurons on lipopolysaccharide-stimulated production of nitric oxide and tumor necrosis factor-alpha by cultured glia. Brain Res. 2000;853:236–44.PubMedCrossRef
27.
go back to reference Morganti JM, Nash KR, Grimmig BA, Ranjit S, Small B, Bickford PC, et al. The soluble isoform of CX3CL1 is necessary for neuroprotection in a mouse model of Parkinson’s disease. J Neurosci. 2012;32:14592–601.PubMedCentralPubMedCrossRef Morganti JM, Nash KR, Grimmig BA, Ranjit S, Small B, Bickford PC, et al. The soluble isoform of CX3CL1 is necessary for neuroprotection in a mouse model of Parkinson’s disease. J Neurosci. 2012;32:14592–601.PubMedCentralPubMedCrossRef
28.
go back to reference Pabon MM, Bachstetter AD, Hudson CE, Gemma C, Bickford PC. CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson’s disease. J Neuroinflammation. 2011;8:9.PubMedCentralPubMedCrossRef Pabon MM, Bachstetter AD, Hudson CE, Gemma C, Bickford PC. CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson’s disease. J Neuroinflammation. 2011;8:9.PubMedCentralPubMedCrossRef
29.
go back to reference Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, et al. Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci. 2006;9:917–24.PubMedCrossRef Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, et al. Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci. 2006;9:917–24.PubMedCrossRef
30.
go back to reference Zhang S, Wang XJ, Tian LP, Pan J, Lu GQ, Zhang YJ, et al. CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson’s disease. J Neuroinflammation. 2011;8:154.PubMedCentralPubMedCrossRef Zhang S, Wang XJ, Tian LP, Pan J, Lu GQ, Zhang YJ, et al. CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson’s disease. J Neuroinflammation. 2011;8:154.PubMedCentralPubMedCrossRef
31.
go back to reference Wang XJ, Zhang S, Yan ZQ, Zhao YX, Zhou HY, Wang Y, et al. Impaired CD200-CD200R-mediated microglia silencing enhances midbrain dopaminergic neurodegeneration: roles of aging, superoxide, NADPH oxidase, and p38 MAPK. Free Radic Biol Med. 2011;50:1094–106.PubMedCrossRef Wang XJ, Zhang S, Yan ZQ, Zhao YX, Zhou HY, Wang Y, et al. Impaired CD200-CD200R-mediated microglia silencing enhances midbrain dopaminergic neurodegeneration: roles of aging, superoxide, NADPH oxidase, and p38 MAPK. Free Radic Biol Med. 2011;50:1094–106.PubMedCrossRef
32.
go back to reference Hu X, Li P, Guo Y, Wang H, Leak RK, Chen S, et al. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke. 2012;43:3063–70.PubMedCrossRef Hu X, Li P, Guo Y, Wang H, Leak RK, Chen S, et al. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke. 2012;43:3063–70.PubMedCrossRef
33.
go back to reference Wang G, Zhang J, Hu X, Zhang L, Mao L, Jiang X, et al. Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. J Cereb Blood Flow Metab. 2013;33:1864–74.PubMedCentralPubMedCrossRef Wang G, Zhang J, Hu X, Zhang L, Mao L, Jiang X, et al. Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. J Cereb Blood Flow Metab. 2013;33:1864–74.PubMedCentralPubMedCrossRef
34.
go back to reference Cagnin A, Kassiou M, Meikle SR, Banati RB. In vivo evidence for microglial activation in neurodegenerative dementia. Acta Neurol Scand Suppl. 2006;185:107–14.PubMedCrossRef Cagnin A, Kassiou M, Meikle SR, Banati RB. In vivo evidence for microglial activation in neurodegenerative dementia. Acta Neurol Scand Suppl. 2006;185:107–14.PubMedCrossRef
35.
go back to reference Tang Y, Li T, Li J, Yang J, Liu H, Zhang XJ, et al. Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease. Cell Death Differ. 2014;21:369–80.PubMedCentralPubMedCrossRef Tang Y, Li T, Li J, Yang J, Liu H, Zhang XJ, et al. Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease. Cell Death Differ. 2014;21:369–80.PubMedCentralPubMedCrossRef
36.
go back to reference Ferrari CC, Pott Godoy MC, Tarelli R, Chertoff M, Depino AM, Pitossi FJ. Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1beta in the substantia nigra. Neurobiol Dis. 2006;24:183–93.PubMedCrossRef Ferrari CC, Pott Godoy MC, Tarelli R, Chertoff M, Depino AM, Pitossi FJ. Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1beta in the substantia nigra. Neurobiol Dis. 2006;24:183–93.PubMedCrossRef
37.
go back to reference McCoy MK, Martinez TN, Ruhn KA, Szymkowski DE, Smith CG, Botterman BR, et al. Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson’s disease. J Neurosci. 2006;26:9365–75.PubMedCentralPubMedCrossRef McCoy MK, Martinez TN, Ruhn KA, Szymkowski DE, Smith CG, Botterman BR, et al. Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson’s disease. J Neurosci. 2006;26:9365–75.PubMedCentralPubMedCrossRef
38.
go back to reference Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML, et al. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J. 2005;19:533–42.PubMedCrossRef Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML, et al. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J. 2005;19:533–42.PubMedCrossRef
39.
go back to reference Yamada T. Lewy bodies in Parkinson’s disease are recognized by antibodies to complement proteins. Acta Neuropathol. 1992;84:5. Yamada T. Lewy bodies in Parkinson’s disease are recognized by antibodies to complement proteins. Acta Neuropathol. 1992;84:5.
40.
go back to reference Theodore S, Cao S, McLean PJ, Standaert DG. Targeted overexpression of human alpha-synuclein triggers microglial activation and an adaptive immune response in a mouse model of Parkinson disease. J Neuropathol Exp Neurol. 2008;67:1149–58.PubMedCentralPubMedCrossRef Theodore S, Cao S, McLean PJ, Standaert DG. Targeted overexpression of human alpha-synuclein triggers microglial activation and an adaptive immune response in a mouse model of Parkinson disease. J Neuropathol Exp Neurol. 2008;67:1149–58.PubMedCentralPubMedCrossRef
41.
go back to reference Beraud D, Maguire-Zeiss KA. Misfolded alpha-synuclein and Toll-like receptors: therapeutic targets for Parkinson’s disease. Parkinsonism Relat Disord. 2012;18 Suppl 1:S17–20.PubMedCentralPubMedCrossRef Beraud D, Maguire-Zeiss KA. Misfolded alpha-synuclein and Toll-like receptors: therapeutic targets for Parkinson’s disease. Parkinsonism Relat Disord. 2012;18 Suppl 1:S17–20.PubMedCentralPubMedCrossRef
42.
43.
go back to reference Koizumi S, Ohsawa K, Inoue K, Kohsaka S. Purinergic receptors in microglia: functional modal shifts of microglia mediated by P2 and P1 receptors. Glia. 2013;61:47–54.PubMedCrossRef Koizumi S, Ohsawa K, Inoue K, Kohsaka S. Purinergic receptors in microglia: functional modal shifts of microglia mediated by P2 and P1 receptors. Glia. 2013;61:47–54.PubMedCrossRef
44.
go back to reference George J, Goncalves FQ, Cristovao G, Rodrigues L, Meyer Fernandes JR, Goncalves T, et al. Different danger signals differently impact on microglial proliferation through alterations of ATP release and extracellular metabolism. Glia. 2015. George J, Goncalves FQ, Cristovao G, Rodrigues L, Meyer Fernandes JR, Goncalves T, et al. Different danger signals differently impact on microglial proliferation through alterations of ATP release and extracellular metabolism. Glia. 2015.
45.
go back to reference Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 2005;8:752–8.PubMedCrossRef Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 2005;8:752–8.PubMedCrossRef
46.
go back to reference Kim YS, Choi DH, Block ML, Lorenzl S, Yang L, Kim YJ, et al. A pivotal role of matrix metalloproteinase-3 activity in dopaminergic neuronal degeneration via microglial activation. FASEB J. 2007;21:179–87.PubMedCrossRef Kim YS, Choi DH, Block ML, Lorenzl S, Yang L, Kim YJ, et al. A pivotal role of matrix metalloproteinase-3 activity in dopaminergic neuronal degeneration via microglial activation. FASEB J. 2007;21:179–87.PubMedCrossRef
47.
go back to reference Pisanu A, Lecca D, Mulas G, Wardas J, Simbula G, Spiga S, et al. Dynamic changes in pro- and anti-inflammatory cytokines in microglia after PPAR-gamma agonist neuroprotective treatment in the MPTPp mouse model of progressive Parkinson’s disease. Neurobiol Dis. 2014;71:280–91.PubMedCrossRef Pisanu A, Lecca D, Mulas G, Wardas J, Simbula G, Spiga S, et al. Dynamic changes in pro- and anti-inflammatory cytokines in microglia after PPAR-gamma agonist neuroprotective treatment in the MPTPp mouse model of progressive Parkinson’s disease. Neurobiol Dis. 2014;71:280–91.PubMedCrossRef
48.
go back to reference Tang Y, Le W. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases. Mol Neurobiol. 2015. Tang Y, Le W. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases. Mol Neurobiol. 2015.
49.
go back to reference Pepe G, Calderazzi G, De Maglie M, Villa A, Vegeto E. Heterogeneous induction of microglia M2a phenotype by central administration of interleukin-4. J Neuroinflammation. 2014;11:1031.CrossRef Pepe G, Calderazzi G, De Maglie M, Villa A, Vegeto E. Heterogeneous induction of microglia M2a phenotype by central administration of interleukin-4. J Neuroinflammation. 2014;11:1031.CrossRef
50.
go back to reference Kim HG, Ju MS, Ha SK, Lee H, Kim SY, Oh MS. Acacetin protects dopaminergic cells against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neuroinflammation in vitro and in vivo. Biol Pharm Bull. 2012;35:1287–94.PubMedCrossRef Kim HG, Ju MS, Ha SK, Lee H, Kim SY, Oh MS. Acacetin protects dopaminergic cells against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neuroinflammation in vitro and in vivo. Biol Pharm Bull. 2012;35:1287–94.PubMedCrossRef
51.
go back to reference Ha SK, Moon E, Lee P, Ryu JH, Oh MS, Kim SY. Acacetin attenuates neuroinflammation via regulation the response to LPS stimuli in vitro and in vivo. Neurochem Res. 2012;37:1560–7.PubMedCrossRef Ha SK, Moon E, Lee P, Ryu JH, Oh MS, Kim SY. Acacetin attenuates neuroinflammation via regulation the response to LPS stimuli in vitro and in vivo. Neurochem Res. 2012;37:1560–7.PubMedCrossRef
52.
go back to reference Tanaka T, Kai S, Matsuyama T, Adachi T, Fukuda K, Hirota K. General anesthetics inhibit LPS-induced IL-1beta expression in glial cells. PLoS One. 2013;8:e82930.PubMedCentralPubMedCrossRef Tanaka T, Kai S, Matsuyama T, Adachi T, Fukuda K, Hirota K. General anesthetics inhibit LPS-induced IL-1beta expression in glial cells. PLoS One. 2013;8:e82930.PubMedCentralPubMedCrossRef
53.
go back to reference Yamada T, Kawamata T, Walker DG, McGeer PL. Vimentin immunoreactivity in normal and pathological human brain tissue. Acta Neuropathol. 1992;84:157–62.PubMedCrossRef Yamada T, Kawamata T, Walker DG, McGeer PL. Vimentin immunoreactivity in normal and pathological human brain tissue. Acta Neuropathol. 1992;84:157–62.PubMedCrossRef
55.
go back to reference Fellner L, Irschick R, Schanda K, Reindl M, Klimaschewski L, Poewe W, et al. Toll-like receptor 4 is required for alpha-synuclein dependent activation of microglia and astroglia. Glia. 2013;61:349–60.PubMedCentralPubMedCrossRef Fellner L, Irschick R, Schanda K, Reindl M, Klimaschewski L, Poewe W, et al. Toll-like receptor 4 is required for alpha-synuclein dependent activation of microglia and astroglia. Glia. 2013;61:349–60.PubMedCentralPubMedCrossRef
56.
go back to reference Gu XL, Long CX, Sun L, Xie C, Lin X, Cai H. Astrocytic expression of Parkinson’s disease-related A53T alpha-synuclein causes neurodegeneration in mice. Mol Brain. 2010;3:12.PubMedCentralPubMedCrossRef Gu XL, Long CX, Sun L, Xie C, Lin X, Cai H. Astrocytic expression of Parkinson’s disease-related A53T alpha-synuclein causes neurodegeneration in mice. Mol Brain. 2010;3:12.PubMedCentralPubMedCrossRef
57.
go back to reference Antonini A, Leenders KL. Dopamine D2 receptors in normal human brain: effect of age measured by positron emission tomography (PET) and [11C]-raclopride. Ann N Y Acad Sci. 1993;695:81–5.PubMedCrossRef Antonini A, Leenders KL. Dopamine D2 receptors in normal human brain: effect of age measured by positron emission tomography (PET) and [11C]-raclopride. Ann N Y Acad Sci. 1993;695:81–5.PubMedCrossRef
58.
go back to reference Shao W, Zhang SZ, Tang M, Zhang XH, Zhou Z, Yin YQ, et al. Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alphaB-crystallin. Nature. 2013;494:90–4.PubMedCrossRef Shao W, Zhang SZ, Tang M, Zhang XH, Zhou Z, Yin YQ, et al. Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alphaB-crystallin. Nature. 2013;494:90–4.PubMedCrossRef
59.
go back to reference Liu Y, Zhou Q, Tang M, Fu N, Shao W, Zhang S, et al. Upregulation of alphaB-crystallin expression in the substantia nigra of patients with Parkinson’s disease. Neurobiol Aging. 2015;36:1686–91.PubMedCrossRef Liu Y, Zhou Q, Tang M, Fu N, Shao W, Zhang S, et al. Upregulation of alphaB-crystallin expression in the substantia nigra of patients with Parkinson’s disease. Neurobiol Aging. 2015;36:1686–91.PubMedCrossRef
60.
go back to reference Zhang Y, Chen Y, Wu J, Manaenko A, Yang P, Tang J, et al. Activation of Dopamine D2 Receptor Suppresses Neuroinflammation Through alphaB-Crystalline by Inhibition of NF-kappaB Nuclear Translocation in Experimental ICH Mice Model. Stroke. 2015;46:2637–46.PubMedCrossRef Zhang Y, Chen Y, Wu J, Manaenko A, Yang P, Tang J, et al. Activation of Dopamine D2 Receptor Suppresses Neuroinflammation Through alphaB-Crystalline by Inhibition of NF-kappaB Nuclear Translocation in Experimental ICH Mice Model. Stroke. 2015;46:2637–46.PubMedCrossRef
61.
go back to reference Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276:2045–7.PubMedCrossRef Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276:2045–7.PubMedCrossRef
62.
go back to reference Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997;388:839–40.PubMedCrossRef Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997;388:839–40.PubMedCrossRef
63.
go back to reference Su X, Maguire-Zeiss KA, Giuliano R, Prifti L, Venkatesh K, Federoff HJ. Synuclein activates microglia in a model of Parkinson’s disease. Neurobiol Aging. 2008;29:1690–701.PubMedCentralPubMedCrossRef Su X, Maguire-Zeiss KA, Giuliano R, Prifti L, Venkatesh K, Federoff HJ. Synuclein activates microglia in a model of Parkinson’s disease. Neurobiol Aging. 2008;29:1690–701.PubMedCentralPubMedCrossRef
64.
go back to reference Codolo G, Plotegher N, Pozzobon T, Brucale M, Tessari I, Bubacco L, et al. Triggering of inflammasome by aggregated alpha-synuclein, an inflammatory response in synucleinopathies. PLoS One. 2013;8:e55375.PubMedCentralPubMedCrossRef Codolo G, Plotegher N, Pozzobon T, Brucale M, Tessari I, Bubacco L, et al. Triggering of inflammasome by aggregated alpha-synuclein, an inflammatory response in synucleinopathies. PLoS One. 2013;8:e55375.PubMedCentralPubMedCrossRef
65.
go back to reference Chesselet MF, Richter F, Zhu C, Magen I, Watson MB, Subramaniam SR. A progressive mouse model of Parkinson’s disease: the Thy1-aSyn (“Line 61”) mice. Neurotherapeutics. 2012;9:297–314.PubMedCentralPubMedCrossRef Chesselet MF, Richter F, Zhu C, Magen I, Watson MB, Subramaniam SR. A progressive mouse model of Parkinson’s disease: the Thy1-aSyn (“Line 61”) mice. Neurotherapeutics. 2012;9:297–314.PubMedCentralPubMedCrossRef
66.
go back to reference Watson MB, Richter F, Lee SK, Gabby L, Wu J, Masliah E, et al. Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein. Exp Neurol. 2012;237:318–34.PubMedCentralPubMedCrossRef Watson MB, Richter F, Lee SK, Gabby L, Wu J, Masliah E, et al. Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein. Exp Neurol. 2012;237:318–34.PubMedCentralPubMedCrossRef
67.
go back to reference Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44:595–600.PubMedCrossRef Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44:595–600.PubMedCrossRef
68.
go back to reference Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004;44:601–7.PubMedCrossRef Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004;44:601–7.PubMedCrossRef
69.
go back to reference Simon-Sanchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet. 2009;41:1308–12.PubMedCentralPubMedCrossRef Simon-Sanchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet. 2009;41:1308–12.PubMedCentralPubMedCrossRef
70.
go back to reference Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C, Kubo M, et al. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson’s disease. Nat Genet. 2009;41:1303–7.PubMedCrossRef Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C, Kubo M, et al. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson’s disease. Nat Genet. 2009;41:1303–7.PubMedCrossRef
71.
go back to reference Moehle MS, Webber PJ, Tse T, Sukar N, Standaert DG, DeSilva TM, et al. LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci. 2012;32:1602–11.PubMedCentralPubMedCrossRef Moehle MS, Webber PJ, Tse T, Sukar N, Standaert DG, DeSilva TM, et al. LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci. 2012;32:1602–11.PubMedCentralPubMedCrossRef
72.
go back to reference Kim B, Yang MS, Choi D, Kim JH, Kim HS, Seol W, et al. Impaired inflammatory responses in murine Lrrk2-knockdown brain microglia. PLoS One. 2012;7:e34693.PubMedCentralPubMedCrossRef Kim B, Yang MS, Choi D, Kim JH, Kim HS, Seol W, et al. Impaired inflammatory responses in murine Lrrk2-knockdown brain microglia. PLoS One. 2012;7:e34693.PubMedCentralPubMedCrossRef
73.
go back to reference Gillardon F, Schmid R, Draheim H. Parkinson’s disease-linked leucine-rich repeat kinase 2(R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicity. Neuroscience. 2012;208:41–8.PubMedCrossRef Gillardon F, Schmid R, Draheim H. Parkinson’s disease-linked leucine-rich repeat kinase 2(R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicity. Neuroscience. 2012;208:41–8.PubMedCrossRef
74.
go back to reference Gardet A, Benita Y, Li C, Sands BE, Ballester I, Stevens C, et al. LRRK2 is involved in the IFN-gamma response and host response to pathogens. J Immunol. 2010;185:5577–85.PubMedCentralPubMedCrossRef Gardet A, Benita Y, Li C, Sands BE, Ballester I, Stevens C, et al. LRRK2 is involved in the IFN-gamma response and host response to pathogens. J Immunol. 2010;185:5577–85.PubMedCentralPubMedCrossRef
75.
go back to reference Hakimi M, Selvanantham T, Swinton E, Padmore RF, Tong Y, Kabbach G, et al. Parkinson’s disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures. J Neural Transm. 2011;118:795–808.PubMedCentralPubMedCrossRef Hakimi M, Selvanantham T, Swinton E, Padmore RF, Tong Y, Kabbach G, et al. Parkinson’s disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures. J Neural Transm. 2011;118:795–808.PubMedCentralPubMedCrossRef
76.
go back to reference Liu Z, Lee J, Krummey S, Lu W, Cai H, Lenardo MJ. The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. Nat Immunol. 2011;12:1063–70.PubMedCentralPubMedCrossRef Liu Z, Lee J, Krummey S, Lu W, Cai H, Lenardo MJ. The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. Nat Immunol. 2011;12:1063–70.PubMedCentralPubMedCrossRef
77.
go back to reference Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–8.PubMedCrossRef Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–8.PubMedCrossRef
78.
go back to reference Frank-Cannon TC, Tran T, Ruhn KA, Martinez TN, Hong J, Marvin M, et al. Parkin deficiency increases vulnerability to inflammation-related nigral degeneration. J Neurosci. 2008;28:10825–34.PubMedCentralPubMedCrossRef Frank-Cannon TC, Tran T, Ruhn KA, Martinez TN, Hong J, Marvin M, et al. Parkin deficiency increases vulnerability to inflammation-related nigral degeneration. J Neurosci. 2008;28:10825–34.PubMedCentralPubMedCrossRef
79.
go back to reference Rodriguez-Navarro JA, Casarejos MJ, Menendez J, Solano RM, Rodal I, Gomez A, et al. Mortality, oxidative stress and tau accumulation during ageing in parkin null mice. J Neurochem. 2007;103:98–114.PubMed Rodriguez-Navarro JA, Casarejos MJ, Menendez J, Solano RM, Rodal I, Gomez A, et al. Mortality, oxidative stress and tau accumulation during ageing in parkin null mice. J Neurochem. 2007;103:98–114.PubMed
80.
go back to reference Casarejos MJ, Menendez J, Solano RM, Rodriguez-Navarro JA, Garcia de Yebenes J, Mena MA. Susceptibility to rotenone is increased in neurons from parkin null mice and is reduced by minocycline. J Neurochem. 2006;97:934–46.PubMedCrossRef Casarejos MJ, Menendez J, Solano RM, Rodriguez-Navarro JA, Garcia de Yebenes J, Mena MA. Susceptibility to rotenone is increased in neurons from parkin null mice and is reduced by minocycline. J Neurochem. 2006;97:934–46.PubMedCrossRef
81.
go back to reference Tran TA, Nguyen AD, Chang J, Goldberg MS, Lee JK, Tansey MG. Lipopolysaccharide and tumor necrosis factor regulate Parkin expression via nuclear factor-kappa B. PLoS One. 2011;6:e23660.PubMedCentralPubMedCrossRef Tran TA, Nguyen AD, Chang J, Goldberg MS, Lee JK, Tansey MG. Lipopolysaccharide and tumor necrosis factor regulate Parkin expression via nuclear factor-kappa B. PLoS One. 2011;6:e23660.PubMedCentralPubMedCrossRef
82.
go back to reference Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science. 2004;304:1158–60.PubMedCrossRef Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science. 2004;304:1158–60.PubMedCrossRef
83.
go back to reference Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010;189:211–21.PubMedCentralPubMedCrossRef Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010;189:211–21.PubMedCentralPubMedCrossRef
84.
go back to reference Akundi RS, Huang Z, Eason J, Pandya JD, Zhi L, Cass WA, et al. Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PLoS One. 2011;6:e16038.PubMedCentralPubMedCrossRef Akundi RS, Huang Z, Eason J, Pandya JD, Zhi L, Cass WA, et al. Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PLoS One. 2011;6:e16038.PubMedCentralPubMedCrossRef
85.
go back to reference Kim J, Byun JW, Choi I, Kim B, Jeong HK, Jou I, et al. PINK1 deficiency enhances inflammatory cytokine release from acutely prepared brain slices. Exp Neurobiol. 2013;22:38–44.PubMedCentralPubMedCrossRef Kim J, Byun JW, Choi I, Kim B, Jeong HK, Jou I, et al. PINK1 deficiency enhances inflammatory cytokine release from acutely prepared brain slices. Exp Neurobiol. 2013;22:38–44.PubMedCentralPubMedCrossRef
86.
87.
go back to reference Bandopadhyay R, Kingsbury AE, Cookson MR, Reid AR, Evans IM, Hope AD, et al. The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease. Brain. 2004;127:420–30.PubMedCrossRef Bandopadhyay R, Kingsbury AE, Cookson MR, Reid AR, Evans IM, Hope AD, et al. The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease. Brain. 2004;127:420–30.PubMedCrossRef
88.
go back to reference Trudler D, Weinreb O, Mandel SA, Youdim MB, Frenkel D. DJ-1 deficiency triggers microglia sensitivity to dopamine toward a pro-inflammatory phenotype that is attenuated by rasagiline. J Neurochem. 2014;129:434–47.PubMedCrossRef Trudler D, Weinreb O, Mandel SA, Youdim MB, Frenkel D. DJ-1 deficiency triggers microglia sensitivity to dopamine toward a pro-inflammatory phenotype that is attenuated by rasagiline. J Neurochem. 2014;129:434–47.PubMedCrossRef
89.
go back to reference Blatteis CM. Role of the OVLT in the febrile response to circulating pyrogens. Prog Brain Res. 1992;91:409–12.PubMedCrossRef Blatteis CM. Role of the OVLT in the febrile response to circulating pyrogens. Prog Brain Res. 1992;91:409–12.PubMedCrossRef
90.
go back to reference Hirsch EC, Hunot S. Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol. 2009;8:382–97.PubMedCrossRef Hirsch EC, Hunot S. Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol. 2009;8:382–97.PubMedCrossRef
91.
go back to reference Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, et al. Blood–brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol. 2005;57:176–9.PubMedCrossRef Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, et al. Blood–brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol. 2005;57:176–9.PubMedCrossRef
92.
go back to reference Faucheux BA, Bonnet AM, Agid Y, Hirsch EC. Blood vessels change in the mesencephalon of patients with Parkinson’s disease. Lancet. 1999;353:981–2.PubMedCrossRef Faucheux BA, Bonnet AM, Agid Y, Hirsch EC. Blood vessels change in the mesencephalon of patients with Parkinson’s disease. Lancet. 1999;353:981–2.PubMedCrossRef
93.
go back to reference Guan J, Pavlovic D, Dalkie N, Waldvogel HJ, O’Carroll SJ, Green CR, et al. Vascular degeneration in Parkinson’s disease. Brain Pathol. 2013;23:154–64.PubMedCrossRef Guan J, Pavlovic D, Dalkie N, Waldvogel HJ, O’Carroll SJ, Green CR, et al. Vascular degeneration in Parkinson’s disease. Brain Pathol. 2013;23:154–64.PubMedCrossRef
94.
go back to reference Yasuda T, Fukuda-Tani M, Nihira T, Wada K, Hattori N, Mizuno Y, et al. Correlation between levels of pigment epithelium-derived factor and vascular endothelial growth factor in the striatum of patients with Parkinson’s disease. Exp Neurol. 2007;206:308–17.PubMedCrossRef Yasuda T, Fukuda-Tani M, Nihira T, Wada K, Hattori N, Mizuno Y, et al. Correlation between levels of pigment epithelium-derived factor and vascular endothelial growth factor in the striatum of patients with Parkinson’s disease. Exp Neurol. 2007;206:308–17.PubMedCrossRef
95.
go back to reference Rite I, Machado A, Cano J, Venero JL. Blood–brain barrier disruption induces in vivo degeneration of nigral dopaminergic neurons. J Neurochem. 2007;101:1567–82.PubMedCrossRef Rite I, Machado A, Cano J, Venero JL. Blood–brain barrier disruption induces in vivo degeneration of nigral dopaminergic neurons. J Neurochem. 2007;101:1567–82.PubMedCrossRef
96.
go back to reference Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest. 2009;119:182–92.PubMedCentralPubMed Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest. 2009;119:182–92.PubMedCentralPubMed
97.
go back to reference Villaran RF, Espinosa-Oliva AM, Sarmiento M, De Pablos RM, Arguelles S, Delgado-Cortes MJ, et al. Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson’s disease. J Neurochem. 2010;114:1687–700.PubMedCrossRef Villaran RF, Espinosa-Oliva AM, Sarmiento M, De Pablos RM, Arguelles S, Delgado-Cortes MJ, et al. Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson’s disease. J Neurochem. 2010;114:1687–700.PubMedCrossRef
98.
go back to reference Beyer MK, Herlofson K, Arsland D, Larsen JP. Causes of death in a community-based study of Parkinson’s disease. Acta Neurol Scand. 2001;103:7–11.PubMedCrossRef Beyer MK, Herlofson K, Arsland D, Larsen JP. Causes of death in a community-based study of Parkinson’s disease. Acta Neurol Scand. 2001;103:7–11.PubMedCrossRef
99.
go back to reference Bu XL, Wang X, Xiang Y, Shen LL, Wang QH, Liu YH, et al. The association between infectious burden and Parkinson’s disease: a case–control study. Parkinsonism Relat Disord. 2015;21:877–81.PubMedCrossRef Bu XL, Wang X, Xiang Y, Shen LL, Wang QH, Liu YH, et al. The association between infectious burden and Parkinson’s disease: a case–control study. Parkinsonism Relat Disord. 2015;21:877–81.PubMedCrossRef
100.
go back to reference Weller C, Oxlade N, Dobbs SM, Dobbs RJ, Charlett A, Bjarnason IT. Role of inflammation in gastrointestinal tract in aetiology and pathogenesis of idiopathic parkinsonism. FEMS Immunol Med Microbiol. 2005;44:129–35.PubMedCrossRef Weller C, Oxlade N, Dobbs SM, Dobbs RJ, Charlett A, Bjarnason IT. Role of inflammation in gastrointestinal tract in aetiology and pathogenesis of idiopathic parkinsonism. FEMS Immunol Med Microbiol. 2005;44:129–35.PubMedCrossRef
101.
go back to reference Przuntek H, Muller T, Riederer P. Diagnostic staging of Parkinson’s disease: conceptual aspects. J Neural Transm. 2004;111:201–16.PubMedCrossRef Przuntek H, Muller T, Riederer P. Diagnostic staging of Parkinson’s disease: conceptual aspects. J Neural Transm. 2004;111:201–16.PubMedCrossRef
102.
go back to reference Nielsen HH, Qiu J, Friis S, Wermuth L, Ritz B. Treatment for Helicobacter pylori infection and risk of Parkinson’s disease in Denmark. Eur J Neurol. 2012;19:864–9.PubMedCentralPubMedCrossRef Nielsen HH, Qiu J, Friis S, Wermuth L, Ritz B. Treatment for Helicobacter pylori infection and risk of Parkinson’s disease in Denmark. Eur J Neurol. 2012;19:864–9.PubMedCentralPubMedCrossRef
103.
go back to reference Tan AH, Mahadeva S, Marras C, Thalha AM, Kiew CK, Yeat CM, et al. Helicobacter pylori infection is associated with worse severity of Parkinson’s disease. Parkinsonism Relat Disord. 2015;21:221–5.PubMedCrossRef Tan AH, Mahadeva S, Marras C, Thalha AM, Kiew CK, Yeat CM, et al. Helicobacter pylori infection is associated with worse severity of Parkinson’s disease. Parkinsonism Relat Disord. 2015;21:221–5.PubMedCrossRef
104.
go back to reference Harms AS, Barnum CJ, Ruhn KA, Varghese S, Trevino I, Blesch A, et al. Delayed dominant-negative TNF gene therapy halts progressive loss of nigral dopaminergic neurons in a rat model of Parkinson’s disease. Mol Ther. 2011;19:46–52.PubMedCentralPubMedCrossRef Harms AS, Barnum CJ, Ruhn KA, Varghese S, Trevino I, Blesch A, et al. Delayed dominant-negative TNF gene therapy halts progressive loss of nigral dopaminergic neurons in a rat model of Parkinson’s disease. Mol Ther. 2011;19:46–52.PubMedCentralPubMedCrossRef
105.
go back to reference McCoy MK, Ruhn KA, Martinez TN, McAlpine FE, Blesch A, Tansey MG. Intranigral lentiviral delivery of dominant-negative TNF attenuates neurodegeneration and behavioral deficits in hemiparkinsonian rats. Mol Ther. 2008;16:1572–9.PubMedCentralPubMedCrossRef McCoy MK, Ruhn KA, Martinez TN, McAlpine FE, Blesch A, Tansey MG. Intranigral lentiviral delivery of dominant-negative TNF attenuates neurodegeneration and behavioral deficits in hemiparkinsonian rats. Mol Ther. 2008;16:1572–9.PubMedCentralPubMedCrossRef
106.
go back to reference Cheng S, Hou J, Zhang C, Xu C, Wang L, Zou X, et al. Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration. Sci Rep. 2015;5:10535.PubMedCentralPubMedCrossRef Cheng S, Hou J, Zhang C, Xu C, Wang L, Zou X, et al. Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration. Sci Rep. 2015;5:10535.PubMedCentralPubMedCrossRef
107.
go back to reference Noble W, Garwood CJ, Hanger DP. Minocycline as a potential therapeutic agent in neurodegenerative disorders characterised by protein misfolding. Prion. 2009;3:78–83.PubMedCentralPubMedCrossRef Noble W, Garwood CJ, Hanger DP. Minocycline as a potential therapeutic agent in neurodegenerative disorders characterised by protein misfolding. Prion. 2009;3:78–83.PubMedCentralPubMedCrossRef
108.
go back to reference Tomas-Camardiel M, Rite I, Herrera AJ, de Pablos RM, Cano J, Machado A, et al. Minocycline reduces the lipopolysaccharide-induced inflammatory reaction, peroxynitrite-mediated nitration of proteins, disruption of the blood–brain barrier, and damage in the nigral dopaminergic system. Neurobiol Dis. 2004;16:190–201.PubMedCrossRef Tomas-Camardiel M, Rite I, Herrera AJ, de Pablos RM, Cano J, Machado A, et al. Minocycline reduces the lipopolysaccharide-induced inflammatory reaction, peroxynitrite-mediated nitration of proteins, disruption of the blood–brain barrier, and damage in the nigral dopaminergic system. Neurobiol Dis. 2004;16:190–201.PubMedCrossRef
109.
go back to reference He Y, Appel S, Le W. Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res. 2001;909:187–93.PubMedCrossRef He Y, Appel S, Le W. Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res. 2001;909:187–93.PubMedCrossRef
110.
go back to reference Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, et al. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci. 2002;22:1763–71.PubMed Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, et al. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci. 2002;22:1763–71.PubMed
111.
go back to reference Diguet E, Fernagut PO, Wei X, Du Y, Rouland R, Gross C, et al. Deleterious effects of minocycline in animal models of Parkinson’s disease and Huntington’s disease. Eur J Neurosci. 2004;19:3266–76.PubMedCrossRef Diguet E, Fernagut PO, Wei X, Du Y, Rouland R, Gross C, et al. Deleterious effects of minocycline in animal models of Parkinson’s disease and Huntington’s disease. Eur J Neurosci. 2004;19:3266–76.PubMedCrossRef
112.
go back to reference Castano A, Herrera AJ, Cano J, Machado A. The degenerative effect of a single intranigral injection of LPS on the dopaminergic system is prevented by dexamethasone, and not mimicked by rh-TNF-alpha, IL-1beta and IFN-gamma. J Neurochem. 2002;81:150–7.PubMedCrossRef Castano A, Herrera AJ, Cano J, Machado A. The degenerative effect of a single intranigral injection of LPS on the dopaminergic system is prevented by dexamethasone, and not mimicked by rh-TNF-alpha, IL-1beta and IFN-gamma. J Neurochem. 2002;81:150–7.PubMedCrossRef
113.
go back to reference Scheinman RI, Gualberto A, Jewell CM, Cidlowski JA, Baldwin Jr AS. Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors. Mol Cell Biol. 1995;15:943–53.PubMedCentralPubMedCrossRef Scheinman RI, Gualberto A, Jewell CM, Cidlowski JA, Baldwin Jr AS. Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors. Mol Cell Biol. 1995;15:943–53.PubMedCentralPubMedCrossRef
114.
go back to reference Kurkowska-Jastrzebska I, Litwin T, Joniec I, Ciesielska A, Przybylkowski A, Czlonkowski A, et al. Dexamethasone protects against dopaminergic neurons damage in a mouse model of Parkinson’s disease. Int Immunopharmacol. 2004;4:1307–18.PubMedCrossRef Kurkowska-Jastrzebska I, Litwin T, Joniec I, Ciesielska A, Przybylkowski A, Czlonkowski A, et al. Dexamethasone protects against dopaminergic neurons damage in a mouse model of Parkinson’s disease. Int Immunopharmacol. 2004;4:1307–18.PubMedCrossRef
115.
go back to reference Iselin-Chaves IA, Grotzsch H, Besson M, Burkhard PR, Savoldelli GL. Naloxone-responsive acute dystonia and parkinsonism following general anaesthesia. Anaesthesia. 2009;64:1359–62.PubMedCrossRef Iselin-Chaves IA, Grotzsch H, Besson M, Burkhard PR, Savoldelli GL. Naloxone-responsive acute dystonia and parkinsonism following general anaesthesia. Anaesthesia. 2009;64:1359–62.PubMedCrossRef
116.
go back to reference Liu B, Du L, Hong JS. Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. J Pharmacol Exp Ther. 2000;293:607–17.PubMed Liu B, Du L, Hong JS. Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. J Pharmacol Exp Ther. 2000;293:607–17.PubMed
117.
go back to reference Di Matteo V, Pierucci M, Di Giovanni G, Di Santo A, Poggi A, Benigno A, et al. Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: an in vivo microdialysis study. Brain Res. 2006;1095:167–77.PubMedCrossRef Di Matteo V, Pierucci M, Di Giovanni G, Di Santo A, Poggi A, Benigno A, et al. Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: an in vivo microdialysis study. Brain Res. 2006;1095:167–77.PubMedCrossRef
118.
go back to reference Mohanakumar KP, Muralikrishnan D, Thomas B. Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced neurotoxicity. Brain Res. 2000;864:281–90.PubMedCrossRef Mohanakumar KP, Muralikrishnan D, Thomas B. Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced neurotoxicity. Brain Res. 2000;864:281–90.PubMedCrossRef
119.
go back to reference Sanchez-Pernaute R, Ferree A, Cooper O, Yu M, Brownell AL, Isacson O. Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson’s disease. J Neuroinflammation. 2004;1:6.PubMedCentralPubMedCrossRef Sanchez-Pernaute R, Ferree A, Cooper O, Yu M, Brownell AL, Isacson O. Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson’s disease. J Neuroinflammation. 2004;1:6.PubMedCentralPubMedCrossRef
121.
go back to reference Starke RM, Chalouhi N, Ding D, Hasan DM. Potential Role of Aspirin in the Prevention of Aneurysmal Subarachnoid Hemorrhage. Cerebrovasc Dis. 2015;39:332–42.PubMedCrossRef Starke RM, Chalouhi N, Ding D, Hasan DM. Potential Role of Aspirin in the Prevention of Aneurysmal Subarachnoid Hemorrhage. Cerebrovasc Dis. 2015;39:332–42.PubMedCrossRef
122.
go back to reference Claria J, Serhan CN. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci U S A. 1995;92:9475–9.PubMedCentralPubMedCrossRef Claria J, Serhan CN. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci U S A. 1995;92:9475–9.PubMedCentralPubMedCrossRef
123.
go back to reference Aubin N, Curet O, Deffois A, Carter C. Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice. J Neurochem. 1998;71:1635–42.PubMedCrossRef Aubin N, Curet O, Deffois A, Carter C. Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice. J Neurochem. 1998;71:1635–42.PubMedCrossRef
124.
go back to reference Manthripragada AD, Schernhammer ES, Qiu J, Friis S, Wermuth L, Olsen JH, et al. Non-steroidal anti-inflammatory drug use and the risk of Parkinson’s disease. Neuroepidemiology. 2011;36:155–61.PubMedCentralPubMedCrossRef Manthripragada AD, Schernhammer ES, Qiu J, Friis S, Wermuth L, Olsen JH, et al. Non-steroidal anti-inflammatory drug use and the risk of Parkinson’s disease. Neuroepidemiology. 2011;36:155–61.PubMedCentralPubMedCrossRef
Metadata
Title
Neuroinflammation in Parkinson’s disease and its potential as therapeutic target
Authors
Qinqin Wang
Yingjun Liu
Jiawei Zhou
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Translational Neurodegeneration / Issue 1/2015
Electronic ISSN: 2047-9158
DOI
https://doi.org/10.1186/s40035-015-0042-0

Other articles of this Issue 1/2015

Translational Neurodegeneration 1/2015 Go to the issue