Parkinson’s disease (PD) is the first and second most prevalent motor and neurodegenerative disease, respectively. The clinical symptoms of PD result from a loss of midbrain dopaminergic (DA) neurons. However, the molecular cause of DA neuron loss remains elusive. Mounting evidence implicates enhanced inflammatory response in the development and progression of PD pathology. This review examines current research connecting PD and inflammatory response.
de LauLMBretelerMM. Epidemiology of Parkinson’s disease. Lancet Neurol2006; 5: 525–35.
2.
JankovicJStacyM. Medical management of levodopa-associated motor complications in patients with Parkinson’s disease. CNS Drugs2007; 21: 677–92.
3.
KastenMChadeATannerCM. Epidemiology of Parkinson’s disease. Handb Clin Neurol2007; 83: 129–51.
4.
McGeerPLItagakiSBoyesBEMcGeerEG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology1988; 38: 1285–91.
5.
TaylorJMMainBSCrackPJ. Neuroinflammation and oxidative stress: co-conspirators in the pathology of Parkinson’s disease. Neurochem Int2013; 62: 803–19.
6.
DukeDCMoranLBPearceRKGraeberMB. The medial and lateral substantia nigra in Parkinson’s disease: mRNA profiles associated with higher brain tissue vulnerability. Neurogenetics2007; 8: 83–94.
7.
ChenHZhangSMHernánMASchwarzschildMAWillettWCColditzGASpeizerFEAscherioA. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch Neurol2003; 60: 1059–64.
8.
ReesKStoweRPatelSIvesNBreenKClarkeCEBen-ShlomoY. Non-steroidal anti-inflammatory drugs as disease-modifying agents for Parkinson’s disease: evidence from observational studies. Cochrane Database Syst Rev2011, pp. CD008454–CD008454.
9.
WahnerADBronsteinJMBordelonYMRitzB. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology2007; 69: 1836–42.
10.
GaoXChenHSchwarzschildMAAscherioA. Use of ibuprofen and risk of Parkinson disease. Neurology2011; 76: 863–9.
11.
HancockDBMartinERStajichJMJewettRStacyMAScottBLVanceJMScottWK. Smoking, caffeine, and nonsteroidal anti-inflammatory drugs in families with Parkinson disease. Arch Neurol2007; 64: 576–80.
12.
HernánMALogroscinoGGarcía RodríguezLA. Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease. Neurology2006; 66: 1097–9.
13.
GoldmanSMTannerCMOakesDBhudhikanokGSGuptaALangstonJW. Head injury and Parkinson’s disease risk in twins. Ann Neurol2006; 60: 65–72.
14.
BowerJHMaraganoreDMPetersonBJAhlskogJERoccaWA. Immunologic diseases, anti-inflammatory drugs, and Parkinson disease: a case-control study. Neurology2006; 67: 494–6.
15.
LeopoldNABara-JimenezWHallettM. Parkinsonism after a wasp sting. Mov Disord1999; 14: 122–7.
16.
MinaultPMadigandMSabouraudO. Pallidostriatal necrosis after Hymenoptera sting. Parkinsonian syndrome. La Nouvelle presse medicale1981; 10: 3725–6.
HeQYuWWuJChenCLouZZhangQZhaoJWangJXiaoB. Intranasal LPS-mediated Parkinson’s model challenges the pathogenesis of nasal cavity and environmental toxins. PLoS One2013; 8: e78418–e78418.
RamseyCPTanseyMG. A survey from 2012 of evidence for the role of neuroinflammation in neurotoxin animal models of Parkinson’s disease and potential molecular targets. Exp Neurol2014; 256: 126–32.
21.
GaoHMKotzbauerPTUryuKLeightSTrojanowskiJQLeeVM. Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J Neurosci2008; 28: 7687–98.
22.
TanseyMGMcCoyMKFrank-CannonTC. Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol2007; 208: 1–25.
23.
BrochardVCombadièreBPrigentALaouarYPerrinABeray-BerthatVBonduelleOAlvarez-FischerDCallebertJLaunayJMDuyckaertsCFlavellRAHirschECHunotS. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest2009; 119: 182–92.
MiyazakiIAsanumaM. Dopaminergic neuron-specific oxidative stress caused by dopamine itself. Acta Med Okayama2008; 62: 141–50.
26.
GiordanoSDarley-UsmarVZhangJ. Autophagy as an essential cellular antioxidant pathway in neurodegenerative disease. Redox Biol2014; 2: 82–90.
27.
RameshGMacLeanAGPhilippMT. Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain. Mediators Inflamm2013; 2013: 480739–480739.
28.
TanseyMGGoldbergMS. Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis2010; 37: 510–8.
29.
PoltorakAHeXSmirnovaILiuMYVan HuffelCDuXBirdwellDAlejosESilvaMGalanosCFreudenbergMRicciardi-CastagnoliPLaytonBBeutlerB. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science1998; 282: 2085–8.
30.
LuYCYehWCOhashiPS. LPS/TLR4 signal transduction pathway. Cytokine2008; 42: 145–51.
31.
CastañoAHerreraAJCanoJMachadoA. Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J Neurochem1998; 70: 1584–92.
32.
HerreraAJCastañoAVeneroJLCanoJMachadoA. The single intranigral injection of LPS as a new model for studying the selective effects of inflammatory reactions on dopaminergic system. Neurobiol Dis2000; 7: 429–47.
33.
LuXBingGHaggT. Naloxone prevents microglia-induced degeneration of dopaminergic substantia nigra neurons in adult rats. Neuroscience2000; 97: 285–91.
34.
Hernández-RomeroMCArgüellesSVillaránRFde PablosRMDelgado-CortésMJSantiagoMHerreraAJCanoJMachadoA. Simvastatin prevents the inflammatory process and the dopaminergic degeneration induced by the intranigral injection of lipopolysaccharide. J Neurochem2008; 105: 445–59.
35.
IravaniMMSadeghianMLeungCCJennerPRoseS. Lipopolysaccharide-induced nigral inflammation leads to increased IL-1β tissue content and expression of astrocytic glial cell line-derived neurotrophic factor. Neurosci Lett2012; 510: 138–42.
36.
BradleyLHFuquaJRichardsonATurchan-CholewoJAiYKelpsKAGlassJDHeXZhangZGrondinRLittrellOMHuettlPPomerleauFGashDMGerhardtGA. Dopamine neuron stimulating actions of a GDNF propeptide. PLoS One2010; 5: e9752–e9752.
37.
ChenSSYangCHaoFLiCLuTZhaoLRDuanWM. Intrastriatal GDNF gene transfer by inducible lentivirus vectors protects dopaminergic neurons in a rat model of parkinsonism. Exp Neurol2014; 261C: 87–96.
HunterRLDragicevicNSeifertKChoiDYLiuMKimHCCassWASullivanPGBingG. Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J Neurochem2007; 100: 1375–86.
41.
ZhouYZhangYLiJLvFZhaoYDuanDXuQ. A comprehensive study on long-term injury to nigral dopaminergic neurons following intracerebroventricular injection of lipopolysaccharide in rats. J Neurochem2012; 123: 771–80.
42.
BickelUGraveBKangYSdel ReyAVoigtK. No increase in blood-brain barrier permeability after intraperitoneal injection of endotoxin in the rat. J Neuroimmunol1998; 85: 131–6.
43.
PanWKastinAJ. TNF-α transport across the blood-brain barrier is abolished in receptor knockout mice. Exp Neurol2002; 174: 193–200.
44.
BanksWA. Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des2005; 11: 973–84.
45.
MorrisonBEMarcondesMCNomuraDKSanchez-AlavezMSanchez-GonzalezASaarIKimKSBartfaiTMaherPSugamaSContiB. Cutting edge: IL-13Rα1 expression in dopaminergic neurons contributes to their oxidative stress-mediated loss following chronic peripheral treatment with lipopolysaccharide. J Immunol2012; 189: 5498–502.
46.
BraakHDel TrediciKRübUde VosRAJansen SteurENBraakE. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging2003; 24: 197–211.
LangstonJWBallardPTetrudJWIrwinI. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science1983; 219: 979–80.
49.
PrzedborskiSJackson-LewisV. Mechanisms of MPTP toxicity. Mov Disord1998; 13: 35–8.
50.
RiachiNJLaMannaJCHarikSI. Entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into the rat brain. J Pharmacol Exp Ther1989; 249: 744–8.
51.
MariesEDassBCollierTJKordowerJHSteece-CollierK. The role of alpha-synuclein in Parkinson's disease: insights from animal models. Nat Rev Neurosci2003; 4: 727–38.
52.
JohannessenJNChiuehCCBurnsRSMarkeySP. Differences in the metabolism of MPTP in the rodent and primate parallel differences in sensitivity to its neurotoxic effects. Life Sci1985; 36: 219–24.
53.
SmeyneRJJackson-LewisV. The MPTP model of Parkinson's disease. Brain Res Mol Brain Res2005; 134: 57–66.
MountMPLiraAGrimesDSmithPDFaucherSSlackRAnismanHHayleySParkDS. Involvement of interferon-gamma in microglial-mediated loss of dopaminergic neurons. J Neurosci2007; 27: 3328–37.
56.
SriramKMathesonJMBenkovicSAMillerDBLusterMIO’CallaghanJP. Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity: implications for Parkinson’s disease. FASEB J2002; 16: 1474–6.
57.
BarciaCRosCMAnneseVGómezARos-BernalFAguado-YeraDMartínez-PagánMEde PablosVFernandez-VillalbaEHerreroMT. IFN-γ signaling, with the synergistic contribution of TNF-α, mediates cell specific microglial and astroglial activation in experimental models of Parkinson’s disease. Cell Death Dis2011; 2: e142–e142.
GiulianiFHaderWYongVW. Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction. J Leukoc Biol2005; 78: 135–43.
60.
DuYMaZLinSDodelRCGaoFBalesKRTriarhouLCChernetEPerryKWNelsonDLLueckeSPhebusLABymasterFPPaulSM. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Proc Natl Acad Sci USA2001; 98: 14669–74.
61.
SwiątkiewiczMZarembaMJoniecICzłonkowskiAKurkowska-JastrzębskaI. Potential neuroprotective effect of ibuprofen, insights from the mice model of Parkinson’s disease. Pharmacol Rep2013; 65: 1227–36.
62.
KhanMMKempurajDThangavelRZaheerA. Protection of MPTP-induced neuroinflammation and neurodegeneration by Pycnogenol. Neurochem Int2013; 62: 379–88.
63.
GeedMGarabaduDAhmadAKrishnamurthyS. Silibinin pretreatment attenuates biochemical and behavioral changes induced by intrastriatal MPP+ injection in rats. Pharmacol Biochem Behav2014; 117: 92–103.
64.
TsaiSJKuoWWLiuWHYinMC. Antioxidative and anti-inflammatory protection from carnosine in the striatum of MPTP-treated mice. J Agric Food Chem2010; 58: 11510–6.
65.
BerryCLa VecchiaCNicoteraP. Paraquat and Parkinson’s disease. Cell Death Differ2010; 17: 1115–25.
66.
PurisaiMGMcCormackALCumineSLiJIslaMZDi MonteDA. Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration. Neurobiol Dis2007; 25: 392–400.
67.
SrivastavaGDixitAYadavSPatelDKPrakashOSinghMP. Resveratrol potentiates cytochrome P450 2 d22-mediated neuroprotection in maneb- and paraquat-induced parkinsonism in the mouse. Free Radic Biol Med2012; 52: 1294–306.
68.
CohenGHeikkilaRE. The generation of hydrogen peroxide, superoxide radical, and hydroxyl radical by 6-hydroxydopamine, dialuric acid, and related cytotoxic agents. J Biol Chem1974; 249: 2447–52.
69.
SadeghianMMarinova-MutafchievaLBroomLDavisJBVirleyDMedhurstADDexterDT. Full and partial peroxisome proliferation-activated receptor-γ agonists, but not δ agonist, rescue of dopaminergic neurons in the 6-OHDA parkinsonian model is associated with inhibition of microglial activation and MMP expression. J Neuroimmunol2012; 246: 69–77.
70.
HeYAppelSLeW. Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res2001; 909: 187–93.
71.
Sánchez-PernauteRFerreeACooperOYuMBrownellALIsacsonO. Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson’s disease. J Neuroinflammation2004; 1: 6–6.
72.
MogiMTogariATanakaKOgawaNIchinoseHNagatsuT. Increase in level of tumor necrosis factor-alpha in 6-hydroxydopamine-lesioned striatum in rats is suppressed by immunosuppressant FK506. Neurosci Lett2000; 289: 165–8.
73.
McCoyMKMartinezTNRuhnKASzymkowskiDESmithCGBottermanBRTanseyKETanseyMG. 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 Neurosci2006; 26: 9365–75.
74.
ShrivastavaPVaibhavKTabassumRKhanAIshratTKhanMMAhmadAIslamFSafhiMM. Anti-apoptotic and anti-inflammatory effect of Piperine on 6-OHDA induced Parkinson's rat model. J Nutr Biochem2013; 24: 680–7.
75.
KumarASharmaNGuptaAKaloniaHMishraJ. Neuroprotective potential of atorvastatin and simvastatin (HMG-CoA reductase inhibitors) against 6-hydroxydopamine (6-OHDA) induced Parkinson-like symptoms. Brain Res2012; 1471: 13–22.
76.
LeeYCLinCHWuRMLinMSLinJWChangCHLaiMS. Discontinuation of statin therapy associates with Parkinson disease: a population-based study. Neurology2013; 81: 410–6.
77.
FriedmanBLahadADresnerYVinkerS. Long-term statin use and the risk of Parkinson’s disease. Am J Managed Care2013; 19: 626–32.
78.
SekiyamaKSugamaSFujitaMSekigawaATakamatsuYWaragaiMTakenouchiTHashimotoM. Neuroinflammation in Parkinson’s disease and related disorders: a lesson from genetically manipulated mouse models of α-synucleinopathies. Parkinsons Dis2012; 2012: 271732–271732.
79.
WilhelmusMMNijlandPGDrukarchBde VriesHEvan HorssenJ. Involvement and interplay of Parkin, PINK1, and DJ1 in neurodegenerative and neuroinflammatory disorders. Free Radic Biol Med2012; 53: 983–92.
80.
PolymeropoulosMHHigginsJJGolbeLIJohnsonWGIdeSEDi IorioGSangesGStenroosESPhoLTSchafferAALazzariniAMNussbaumRLDuvoisinRC. Mapping of a gene for Parkinson’s disease to chromosome 4q21–q23. Science1996; 274: 1197–9.
81.
ChandraSChenXRizoJJahnRSudhofTC. A broken alpha-helix in folded alpha-Synuclein. J Biol Chem2003; 278: 15313–8.
82.
ConwayKALeeSJRochetJCDingTTHarperJDWilliamsonRELansburyPT. Accelerated oligomerization by Parkinson’s disease linked alpha-synuclein mutants. Ann NY Acad Sci2000; 920: 42–5.
83.
IbáñezPBonnetAMDébargesBLohmannETisonFPollakPAgidYDürrABriceA. Causal relation between alpha-synuclein gene duplication and familial Parkinson’s disease. Lancet2004; 364: 1169–71.
84.
KimHJ. Alpha-synuclein expression in patients with Parkinson’s disease: a clinician’s perspective. Exp Neurobiol2013; 22: 77–83.
85.
CouchYAlvarez-ErvitiLSibsonNRWoodMJAnthonyDC. The acute inflammatory response to intranigral α-synuclein differs significantly from intranigral lipopolysaccharide and is exacerbated by peripheral inflammation. J Neuroinflammation2011; 8: 166–166.
86.
GaoHMZhangFZhouHKamWWilsonBHongJS. Neuroinflammation and α-synuclein dysfunction potentiate each other, driving chronic progression of neurodegeneration in a mouse model of Parkinson's disease. Environ Health Perspect2011; 119: 807–14.
PoonHFFrasierMShreveNCalabreseVWolozinBButterfieldDA. Mitochondrial associated metabolic proteins are selectively oxidized in A30P alpha-synuclein transgenic mice—a model of familial Parkinson’s disease. Neurobiol Dis2005; 18: 492–8.
89.
LeeMHyunDHalliwellBJennerP. Effect of the overexpression of wild-type or mutant alpha-synuclein on cell susceptibility to insult. J Neurochem2001; 76: 998–1009.
90.
WatsonMBRichterFLeeSKGabbyLWuJMasliahEEffrosRBChesseletMF. Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein. Exp Neurol2012; 237: 318–34.
91.
PapachroniKKNinkinaNPapapanagiotouAHadjigeorgiouGMXiromerisiouGPapadimitriouAKalofoutisABuchmanVL. Autoantibodies to alpha-synuclein in inherited Parkinson's disease. J Neurochem2007; 101: 749–56.
92.
MasliahERockensteinEAdameAAlfordMCrewsLHashimotoMSeubertPLeeMGoldsteinJChilcoteTGamesDSchenkD. Effects of alpha-synuclein immunization in a mouse model of Parkinson’s disease. Neuron2005; 46: 857–68.
93.
DesplatsPLeeHJBaeEJPatrickCRockensteinECrewsLSpencerBMasliahELeeSJ. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci USA2009; 106: 13010–5.
94.
Paisán-RuízCJainSEvansEWGilksWPSimónJvan der BrugMLópez de MunainAAparicioSGilAMKhanNJohnsonJMartinezJRNichollDCarreraIMPenaASde SilvaRLeesAMartí-MassóJFPérez-TurJWoodNWSingletonAB. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron2004; 44: 595–600.
95.
ZimprichABiskupSLeitnerPLichtnerPFarrerMLincolnSKachergusJHulihanMUittiRJCalneDBStoesslAJPfeifferRFPatengeNCarbajalICViereggePAsmusFMüller-MyhsokBDicksonDWMeitingerTStromTMWszolekZKGasserT. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron2004; 44: 601–7.
96.
GoldwurmSDi FonzoASimonsEJRohéCFZiniMCanesiMTeseiSZecchinelliAAntoniniAMarianiCMeucciNSacilottoGSironiFSalaniGFerreiraJChienHFFabrizioEVanacoreNDalla LiberaAStocchiFDiromaCLambertiPSampaioCMecoGBarbosaEBertoli-AvellaAMBreedveldGJOostraBAPezzoliGBonifatiV. The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor. J Med Genet2005; 42: e65–e65.
RussoIBubaccoLGreggioE. LRRK2 and neuroinflammation: partners in crime in Parkinson's disease?J Neuroinflammation2014; 11: 52–52.
99.
ZhangFRHuangWChenSMSunLDLiuHLiYCuiYYanXXYangHTYangRDChuTSZhangCZhangLHanJWYuGQQuanCYuYXZhangZShiBQZhangLHChengHWangCYLinYZhengHFFuXAZuoXBWangQLongHSunYPChengYLTianHQZhouFSLiuHXLuWSHeSMDuWLShenMJinQYWangYLowHQErwinTYangNHLiJYZhaoXJiaoYLMaoLGYinGJiangZXWangXDYuJPHuZHGongCHLiuYQLiuRYWangDMWeiDLiuJXCaoWKCaoHZLiYPYanWGWeiSYWangKJHibberdMLYangSZhangXJLiuJJ. Genomewide association study of leprosy. N Engl J Med2009; 361: 2609–18.
100.
FrankeAMcGovernDPBarrettJCWangKRadford-SmithGLAhmadTLeesCWBalschunTLeeJRobertsRAndersonCABisJCBumpsteadSEllinghausDFestenEMGeorgesMGreenTHarituniansTJostinsLLatianoAMathewCGMontgomeryGWPrescottNJRaychaudhuriSRotterJISchummPSharmaYSimmsLATaylorKDWhitemanDWijmengaCBaldassanoRNBarclayMBaylessTMBrandSBüningCCohenAColombelJFCottoneMStronatiLDensonTDe VosMD'IncaRDubinskyMEdwardsCFlorinTFranchimontDGearryRGlasJVan GossumAGutherySLHalfvarsonJVerspagetHWHugotJPKarbanALaukensDLawranceILemannMLevineALibioulleCLouisEMowatCNewmanWPanésJPhillipsAProctorDDRegueiroMRussellRRutgeertsPSandersonJSansMSeiboldFSteinhartAHStokkersPCTorkvistLKullak-UblickGWilsonDWaltersTTarganSRBrantSRRiouxJDD'AmatoMWeersmaRKKugathasanSGriffithsAMMansfieldJCVermeireSDuerrRHSilverbergMSSatsangiJSchreiberSChoJHAnneseVHakonarsonHDalyMJParkesM. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet2010; 42: 1118–25.
101.
GardetABenitaYLiCSandsBEBallesterIStevensCKorzenikJRRiouxJDDalyMJXavierRJPodolskyDK. LRRK2 is involved in the IFN-gamma response and host response to pathogens. J Immunol2010; 185: 5577–85.
ParkJLeeSBLeeSKimYSongSKimSBaeEKimJShongMKimJMChungJ. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature2006; 441: 1157–61.
104.
GreeneJCWhitworthAJKuoIAndrewsLAFeanyMBPallanckLJ. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci USA2003; 100: 4078–83.
105.
ChungKKThomasBLiXPletnikovaOTroncosoJCMarshLDawsonVLDawsonTM. S-nitrosylation of parkin regulates ubiquitination and compromises parkin’s protective function. Science2004; 304: 1328–31.
106.
KurodaYMitsuiTKunishigeMMatsumotoT. Parkin affects mitochondrial function and apoptosis in neuronal and myogenic cells. Biochem Biophys Res Commun2006; 348: 787–93.
107.
TranTANguyenADChangJGoldbergMSLeeJKTanseyMG. Lipopolysaccharide and tumor necrosis factor regulate Parkin expression via nuclear factor-kappa B. PLoS One2011; 6: e23660–e23660.
108.
ShendelmanSJonasonAMartinatCLeeteTAbeliovichA. DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation. PLoS Biol2004; 2: e362–e362.
109.
BandopadhyayRKingsburyAECooksonMRReidAREvansIMHopeADPittmanAMLashleyTCanet-AvilesRMillerDWMcLendonCStrandCLeonardAJAbou-SleimanPMHealyDGArigaHWoodNWde SilvaRReveszTHardyJALeesAJ. The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease. Brain2004; 127: 420–30.
110.
KahlePJWaakJGasserT. DJ-1 and prevention of oxidative stress in Parkinson’s disease and other age-related disorders. Free Radic Biol Med2009; 47: 1354–61.
111.
WaakJWeberSSWaldenmaierAGörnerKAlunni-FabbroniMSchellHVogt-WeisenhornDPhamTTReumersVBaekelandtVWurstWKahlePJ. Regulation of astrocyte inflammatory responses by the Parkinson’s disease-associated gene DJ-1. FASEB J2009; 23: 2478–89.
112.
Manning-BoğABCaudleWMPerezXAReaneySHPaletzkiRIslaMZChouVPMcCormackALMillerGWLangstonJWGerfenCRDimonteDA. Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is mediated by the dopamine transporter. Neurobiol Dis2007; 27: 141–50.
113.
NguyenTAFrank-CannonTMartinezTNRuhnKAMarvinMCaseyBTreviñoIHongJJGoldbergMSTanseyMG. Analysis of inflammation-related nigral degeneration and locomotor function in DJ-1(-/-) mice. J Neuroinflammation2013; 10: 50–50.
114.
HaqueMEMountMPSafarpourFAbdel-MessihECallaghanSMazerolleCKitadaTSlackRSWallaceVShenJAnismanHParkDS. Inactivation of Pink1 gene in vivo sensitizes dopamine-producing neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and can be rescued by autosomal recessive Parkinson disease genes, Parkin or DJ-1. J Biol Chem2012; 287: 23162–70.
115.
AkundiRSHuangZEasonJPandyaJDZhiLCassWASullivanPGBüelerH. Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice. PLoS One2011; 6: e16038–e16038.