Inflammation in Parkinson’s disease: Causative or epiphenomenal?

Subcellular Biochemistry

Volumn 42, Issue , 2007, Pages 249-279

  Hald, Andreas ^a   van Beek, Johan ^b   Lotharius, Julie ^b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b H LUNDBECK A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; DOPAMINE; NONSTEROID ANTIINFLAMMATORY AGENT;

CHEMICALLY INDUCED DISORDER; CHRONIC DISEASE; DRUG EFFECT; HUMAN; INFLAMMATION; INTOXICATION; METABOLISM; MICROGLIA; OXIDATIVE STRESS; PATHOLOGY; REVIEW; RISK FACTOR; SUBSTANTIA NIGRA;

1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CHRONIC DISEASE; DOPAMINE; HUMANS; INFLAMMATION; MICROGLIA; MPTP POISONING; OXIDATIVE STRESS; RISK FACTORS; SUBSTANTIA NIGRA;

EID: 34547593070     PISSN: 03060225     EISSN: None     Source Type: Book Series    
DOI: 10.1007/1-4020-5688-5_12     Document Type: Article

References (202)

1. Abou-Sleiman PM, Muqit MM, Wood NW (2006) Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci 7: 207-219.
2. Ahsan H, Ali A, Ali R (2003) Oxygen free radicals and systemic autoimmunity. Clin Exp Immunol 131: 398-404.
3. Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ (2003) Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 289: 2819-2826.
4. Akaneya Y, Takahashi M, Hatanaka H (1995) Interleukin-1 beta enhances survival and interleukin-6 protects against MPP+ neurotoxicity in cultures of fetal rat dopaminergic neurons. Exp Neurol 136: 44-52.
5. Allan SM, Rothwell NJ (2001) Cytokines and acute neurodegeneration. Nat Rev Neurosci 2: 734-744.
6. Aloisi F (1999) The role of microglia and astrocytes in CNS immune surveillance and immunopathology. Adv Exp Med Biol 468: 123-133.
7. Arimoto T, Bing G (2003) Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration. Neurobiol Dis 12: 35-45.
8. Asano T, Mori T, Shimoda T, Shinagawa R, Satoh S, Yada N, Katsumata S, Matsuda S, Kagamiishi Y, Tateishi N (2005) Arundic acid (ONO-2506) ameliorates delayed ischemic brain damage by preventing astrocytic overproduction of S100B. Curr Drug Targets CNS Neurol Disord 4: 127-142.
9. Barbeito LH, Pehar M, Cassina P, Vargas MR, Peluffo H, Viera L, Estevez AG, Beckman JS (2004) A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis. Brain Res Brain Res Rev 47: 263-274.
10. Barger SW, Horster D, Furukawa K, Goodman Y, Krieglstein J, Mattson MP (1995) Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and Ca2+ accumulation. Proc Natl Acad Sci U S A 92: 9328-9332.
11. Barnum SR (2002) Complement in central nervous system inflammation. Immunol Res 26: 7-13.
12. Batchelor PE, Liberatore GT, Wong JY, Porritt MJ, Frerichs F, Donnan GA, Howells DW (1999) Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J Neurosci 19: 1708-1716.
13. Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271: C1424-C1437.
14. Benveniste EN, Sparacio SM, Bethea JR (1989) Tumor necrosis factor-alpha enhances interferongamma-mediated class II antigen expression on astrocytes. J Neuroimmunol 25: 209-219.
15. Benveniste EN, Sparacio SM, Norris JG, Grenett HE, Fuller GM (1990) Induction and regulation of interleukin-6 gene expression in rat astrocytes. J Neuroimmunol 30: 201-212.
16. Berman SB, Hastings TG (1999) Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson's disease. J Neurochem 73: 1127-1137.
17. Berman SB, Hastings TG (1997) Inhibition of glutamate transport in synaptosomes by dopamine oxidation and reactive oxygen species. J Neurochem 69: 1185-1195.
18. Berman SB, Zigmond MJ, Hastings TG (1996) Modification of dopamine transporter function: effect of reactive oxygen species and dopamine. J Neurochem 67: 593-600.
19. Betarbet R, Sherer TB, Greenamyre JT (2005) Ubiquitin-proteasome system and Parkinson's diseases. Exp Neurol 191(1): S17-S27.
20. Blum-Degen D, Muller T, Kuhn W, Gerlach M, Przuntek H, Riederer P (1995) Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci Lett 202: 17-20.
21. Boka G, Anglade P, Wallach D, Javoy-Agid F, Agid Y, Hirsch EC (1994) Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease. Neurosci Lett 172: 151-154.
22. Bonifati V, Oostra BA, Heutink P (2004) Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson's disease. J Mol Med 82: 163-174.
23. Breidert T, Callebert J, Heneka MT, Landreth G, Launay JM, Hirsch EC (2002) Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson's disease. J Neurochem 82: 615-624.
24. Cacquevel M, Lebeurrier N, Cheenne S, Vivien D (2004) Cytokines in neuroinflammation and Alzheimer's disease. Curr Drug Targets 5: 529-534.
25. Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MB, Mucke L (1993) Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci U S A 90: 10061-10065.
26. Carrasco E, Casper D, Werner P (2005) Dopaminergic neurotoxicity by 6-OHDA and MPP+: differential requirement for neuronal cyclooxygenase activity. J Neurosci Res 81: 121-131.
27. Castano A, Herrera AJ, Cano J, Machado A (1998) Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J Neurochem 70: 1584-1592.
28. Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A (2005) Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann Neurol 58: 963-967.
29. Chen H, Zhang SM, Hernan MA, Schwarzschild MA, Willett WC, Colditz GA, Speizer FE, Ascherio A (2003) Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch Neurol 60: 1059-1064.
30. Chen LW, Wei LC, Qiu Y, Liu HL, Rao ZR, Ju G, Chan YS (2002) Significant up-regulation of nestin protein in the neostriatum of MPTP-treated mice. Are the striatal astrocytes regionally activated after systemic MPTP administration? Brain Res 925: 9-17.
31. Chun KS, Surh YJ (2004) Signal transduction pathways regulating cyclooxygenase-2 expression: potential molecular targets for chemoprevention. Biochem Pharmacol 68: 1089-1100.
32. Chung IY, Benveniste EN (1990) Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta. J Immunol 144: 2999-3007.
33. Cicchetti F, Brownell AL, Williams K, Chen YI, Livni E, Isacson O (2002) Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci 15: 991-998.
34. Ciesielska A, Joniec I, Przybylkowski A, Gromadzka G, Kurkowska-Jastrzebska I, Czlonkowska A, Czlonkowski A (2003) Dynamics of expression of the mRNA for cytokines and inducible nitric synthase in a murine model of the Parkinson's disease. Acta Neurobiol Exp (Wars) 63: 117-126.
35. Clarke DJ, Branton RL (2002) A role for tumor necrosis factor alpha in death of dopaminergic neurons following neural transplantation. Exp Neurol 176: 154-162.
36. Consilvio C, Vincent AM, Feldman EL (2004) Neuroinflammation, COX-2, and ALS-a dual role? Exp Neurol 187: 1-10.
37. Cookson MR, Xiromerisiou G, Singleton A (2005) How genetics research in Parkinson's disease is enhancing understanding of the common idiopathic forms of the disease. Curr Opin Neurol 18: 706-711.
38. Czlonkowska A, Kohutnicka M, Kurkowska-Jastrzebska I, Czlonkowski A (1996) Microglial reaction in MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) induced Parkinson's disease mice model. Neurodegeneration 5: 137-143.
39. Damier P, Hirsch EC, Zhang P, Agid Y, Javoy-Agid F (1993) Glutathione peroxidase, glial cells and Parkinson's disease. Neuroscience 52: 1-6.
40. Dauer W, Przedborski S (2003) Parkinson's disease: mechanisms and models. Neuron 39: 889-909.
41. Defazio G, Dal TR, Benvegnu D, Minozzi MC, Cananzi AR, Leon A (1994) Parkinsonian serum carries complement-dependent toxicity for rat mesencephalic dopaminergic neurons in culture. Brain Res 633: 206-212.
42. Delgado M, Ganea D (2003) Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson's disease by blocking microglial activation. FASEB J 17: 944-946.
43. Dexter DT, Wells FR, Lees AJ, Agid F, Agid Y, Jenner P, Marsden CD (1989) Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease. J Neurochem 52: 1830-1836.
44. Diguet E, Fernagut PO, Wei X, Du Y, Rouland R, Gross C, Bezard E, Tison F (2004) Deleterious effects of minocycline in animal models of Parkinson's disease and Huntington's disease. Eur J Neurosci 19: 3266-3276.
45. Dringen R, Hirrlinger J (2003) Glutathione pathways in the brain. Biol Chem 384: 505-516.
46. Estevez AG, Jordan J (2002) Nitric oxide and superoxide, a deadly cocktail. Ann N Y Acad Sci 962: 207-211.
47. Fahrig T, Gerlach I, Horvath E (2005) A synthetic derivative of the natural product rocaglaol is a potent inhibitor of cytokine-mediated signaling and shows neuroprotective activity in vitro and in animal models of Parkinson's disease and traumatic brain injury. Mol Pharmacol 67: 1544-1555.
48. Falsig J, Latta M, Leist M (2004) Defined inflammatory states in astrocyte cultures: correlation with susceptibility towards CD95-driven apoptosis. J Neurochem 88: 181-193.
49. Fearnley JM, Lees AJ (1991) Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain 114 (Pt 5): 2283-2301.
50. Feng Z, Li D, Fung PC, Pei Z, Ramsden DB, Ho SL (2003) COX-2-deficient mice are less prone to MPTP-neurotoxicity than wild-type mice. Neuroreport 14: 1927-1929.
51. Feng ZH, Wang TG, Li DD, Fung P, Wilson BC, Liu B, Ali SF, Langenbach R, Hong JS (2002) Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridineinduced damage of dopaminergic neurons in the substantia nigra. Neurosci Lett 329: 354-358.
52. Fisher J, Mizrahi T, Schori H, Yoles E, Levkovitch-Verbin H, Haggiag S, Revel M, Schwartz M (2001) Increased post-traumatic survival of neurons in IL-6-knockout mice on a background of EAE susceptibility. J Neuroimmunol 119: 1-9.
53. Floor E, Wetzel MG (1998) Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay. J Neurochem 70: 268-275.
54. Fontaine V, Mohand-Said S, Hanoteau N, Fuchs C, Pfizenmaier K, Eisel U (2002) Neurodegenerative and neuroprotective effects of tumor Necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2. J Neurosci 22: RC216.
55. Frank MM, Fries LF (1991) The role of complement in inflammation and phagocytosis. Immunol Today 12: 322-326.
56. Gao HM, Hong JS, Zhang W, Liu B (2003a) Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson's disease. J Neurosci 23: 1228-1236.
57. Gao HM, Jiang J, Wilson B, Zhang W, Hong JS, Liu B (2002) Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. J Neurochem 81: 1285-1297.
58. Gao HM, Liu B, Zhang W, Hong JS (2003b) Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson's disease. FASEB J 17: 1954-1956.
59. Gayle DA, Ling Z, Tong C, Landers T, Lipton JW, Carvey PM (2002) Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factor-alpha, interleukin-1beta, and nitric oxide. Brain Res Dev Brain Res 133: 27-35.
60. Gerlach M, Ben-Shachar D, Riederer P, Youdim MB (1994) Altered brain metabolism of iron as a cause of neurodegenerative diseases? J Neurochem 63: 793-807.
61. Gesi M, Santinami A, Ruffoli R, Conti G, Fornai F (2001) Novel aspects of dopamine oxidative metabolism (confounding outcomes take place of certainties). Pharmacol Toxicol 89: 217-224.
62. Gierse JK, McDonald JJ, Hauser SD, Rangwala SH, Koboldt CM, Seibert K (1996) A single amino acid difference between cyclooxygenase-1 (COX-1) and-2 (COX-2) reverses the selectivity of COX-2 specific inhibitors. J Biol Chem 271: 15810-15814.
63. Giulian D, Woodward J, Young DG, Krebs JF, Lachman LB (1988) Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J Neurosci 8: 2485-2490.
64. Gotz ME, Kunig G, Riederer P, Youdim MB (1994) Oxidative stress: free radical production in neural degeneration. Pharmacol Ther 63: 37-122.
65. Graham DG (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14: 633-643.
66. Graham DY, Chan FK (2004) Is the use of COX-2 inhibitors in gastroenterology cost-effective? Nat Clin Pract Gastroenterol Hepatol 1: 60-61.
67. Greenamyre JT, Hastings TG (2004) Biomedicine. Parkinson's-divergent causes, convergent mechanisms. Science 304: 1120-1122.
68. Guan Z, Buckman SY, Miller BW, Springer LD, Morrison AR (1998) Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells. J Biol Chem 273: 28670-28676.
69. Hald A, Lotharius J (2005) Oxidative stress and inflammation in Parkinson's disease: is there a causal link? Exp Neurol 193: 279-290.
70. Hanisch UK (2002) Microglia as a source and target of cytokines. Glia 40: 140-155.
71. Hastings TG (1995) Enzymatic oxidation of dopamine: the role of prostaglandin H synthase. J Neurochem 64: 919-924.
72. Haussermann P, Kuhn W, Przuntek H, Muller T (2001) Integrity of the blood-cerebrospinal fluid barrier in early Parkinson's disease. Neurosci Lett 300: 182-184.
73. Hemmer K, Fransen L, Vanderstichele H, Vanmechelen E, Heuschling P (2001) An in vitro model for the study of microglia-induced neurodegeneration: involvement of nitric oxide and tumor necrosis factor-alpha. Neurochem Int 38: 557-565.
74. Herrera AJ, Castano A, Venero JL, Cano J, Machado A (2000) The single intranigral injection of LPS as a new model for studying the selective effects of inflammatory reactions on dopaminergic system. Neurobiol Dis 7: 429-447.
75. Hertz L (2004) The astrocyte-neuron lactate shuttle: a challenge of a challenge. J Cereb Blood Flow Metab 24: 1241-1248.
76. Hertz L, Dringen R, Schousboe A, Robinson SR (1999) Astrocytes: glutamate producers for neurons. J Neurosci Res 57: 417-428.
77. Hirsch E, Graybiel AM, Agid YA (1988) Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature 334: 345-348.
78. Hirsch EC, Brandel JP, Galle P, Javoy-Agid F, Agid Y (1991) Iron and aluminum increase in the substantia nigra of patients with Parkinson's disease: an X-ray microanalysis. J Neurochem 56: 446-451.
79. Hirsch EC, Breidert T, Rousselet E, Hunot S, Hartmann A, Michel PP (2003) The role of glial reaction and inflammation in Parkinson's disease. Ann N Y Acad Sci 991: 214-228.
80. Hla T, Neilson K (1992) Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci U S A 89: 7384-7388.
81. Hoglinger GU, Carrard G, Michel PP, Medja F, Lombes A, Ruberg M, Friguet B, Hirsch EC (2003) Dysfunction of mitochondrial complex I and the proteasome: interactions between two biochemical deficits in a cellular model of Parkinson's disease. J Neurochem 86: 1297-1307.
82. Hoozemans JJ, Veerhuis R, Janssen I, van Elk EJ, Rozemuller AJ, Eikelenboom P (2002) The role of cyclo-oxygenase 1 and 2 activity in prostaglandin E(2) secretion by cultured human adult microglia: implications for Alzheimer's disease. Brain Res 951: 218-226.
83. Hornykiewicz O (1998) Biochemical aspects of Parkinson's disease. Neurology 51: S2-S9.
84. Hunot S, Dugas N, Faucheux B, Hartmann A, Tardieu M, Debre P, Agid Y, Dugas B, Hirsch EC (1999) FcepsilonRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J Neurosci 19: 3440-3447.
85. Hunot S, Vila M, Teismann P, Davis RJ, Hirsch EC, Przedborski S, Rakic P, Flavell RA (2004) JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A 101: 665-670.
86. Ikeda-Matsuo Y, Ikegaya Y, Matsuki N, Uematsu S, Akira S, Sasaki Y (2005) Microglia-specific expression of microsomal prostaglandin E2 synthase-1 contributes to lipopolysaccharide-induced prostaglandin E2 production. J Neurochem 94: 1546-1558.
87. Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y (2003) Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson's disease brains. Acta Neuropathol (Berl) 106: 518-526.
88. In t' Veld, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, Breteler MM, Stricker BH (2001) Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med 345: 1515-1521.
89. Iravani MM, Kashefi K, Mander P, Rose S, Jenner P (2002) Involvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegeneration. Neuroscience 110: 49-58.
90. Jellinger KA (1999) Post mortem studies in Parkinson's disease-is it possible to detect brain areas for specific symptoms? J Neural Transm Suppl 56: 1-29.
91. Kassiotis G, Kollias G (2001) Uncoupling the proinflammatory from the immunosuppressive properties of tumor necrosis factor (TNF) at the p55 TNF receptor level: implications for pathogenesis and therapy of autoimmune demyelination. J Exp Med 193: 427-434.
92. Kato H, Araki T, Imai Y, Takahashi A, Itoyama Y (2003) Protection of dopaminergic neurons with a novel astrocyte modulating agent (R)-α-β-2-propyloctanoic acid (ONO-2506) in an MPTP-mouse model of Parkinson's disease. J Neurol Sci 208: 9-15.
93. Kato H, Kurosaki R, Oki C, Araki T (2004) Arundic acid, an astrocyte-modulating agent, protects dopaminergic neurons against MPTP neurotoxicity in mice. Brain Res 1030: 66-73.
94. Kennedy LJ, Moore K Jr, Caulfield JL, Tannenbaum SR, Dedon PC (1997) Quantitation of 8-oxoguanine and strand breaks produced by four oxidizing agents. Chem Res Toxicol 10: 386-392.
95. Khan FH, Saha M, Chakrabarti S (2001) Dopamine induced protein damage in mitochondrialsynaptosomal fraction of rat brain. Brain Res 895: 245-249.
96. Kish SJ, Shannak K, Hornykiewicz O (1988) Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. N Engl J Med 318: 876-880.
97. Knott C, Stern G, Wilkin GP (2000) Inflammatory regulators in Parkinson's disease: iNOS, lipocortin-1, and cyclooxygenases-1 and-2. Mol Cell Neurosci 16: 724-739.
98. Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, Hendrikse NH (2005) Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol 57: 176-179.
99. Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19: 312-318.
100. Kuhn DM, Arthur RE Jr, Thomas DM, Elferink LA (1999) Tyrosine hydroxylase is inactivated by catechol-quinones and converted to a redox-cycling quinoprotein: possible relevance to Parkinson's disease. J Neurochem 73: 1309-1317.
101. Kumagai T, Matsukawa N, Kaneko Y, Kusumi Y, Mitsumata M, Uchida K (2004) A lipid peroxidationderived inflammatory mediator: identification of 4-hydroxy-2-nonenal as a potential inducer of cyclooxygenase-2 in macrophages. J Biol Chem 279: 48389-48396.
102. Ladenheim B, Krasnova IN, Deng X, Oyler JM, Polettini A, Moran TH, Huestis MA, Cadet JL (2000) Methamphetamine-induced neurotoxicity is attenuated in transgenic mice with a null mutation for interleukin-6. Mol Pharmacol 58: 1247-1256.
103. Langston JW, Forno LS, Tetrud J, Reeves AG, Kaplan JA, Karluk D (1999) Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine exposure. Ann Neurol 46: 598-605.
104. Le W, Rowe D, Xie W, Ortiz I, He Y, Appel SH (2001) Microglial activation and dopaminergic cell injury: an in vitro model relevant to Parkinson's disease. J Neurosci 21: 8447-8455.
105. Lee SC, Dickson DW, Liu W, Brosnan CF (1993) Induction of nitric oxide synthase activity in human astrocytes by interleukin-1 beta and interferon-gamma. J Neuroimmunol 46: 19-24.
106. Lee SH, Soyoola E, Chanmugam P, Hart S, Sun W, Zhong H, Liou S, Simmons D, Hwang D (1992) Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. J Biol Chem 267: 25934-25938.
107. Leu CM, Wong FH, Chang C, Huang SF, Hu CP (2003) Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways. Oncogene 22: 7809-7818.
108. Liberatore GT, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WG, Dawson VL, Dawson TM, Przedborski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5: 1403-1409.
109. Liberto CM, Albrecht PJ, Herx LM, Yong VW, Levison SW (2004) Pro-regenerative properties of cytokine-activated astrocytes. J Neurochem 89: 1092-1100.
110. Lim GP, Yang F, Chu T, Chen P, Beech W, Teter B, Tran T, Ubeda O, Ashe KH, Frautschy SA, Cole GM (2000) Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J Neurosci 20: 5709-5714.
111. Liu B, Gao HM, Wang JY, Jeohn GH, Cooper CL, Hong JS (2002) Role of nitric oxide in inflammationmediated neurodegeneration. Ann N Y Acad Sci 962: 318-331.
112. Liu Y, Qin L, Li G, Zhang W, An L, Liu B, Hong JS (2003) Dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation. J Pharmacol Exp Ther 305: 212-218.
113. Lotharius J, Brundin P (2002a) Pathogenesis of Parkinson's disease: dopamine, vesicles and alphasynuclein. Nat Rev Neurosci 3: 932-942.
114. Lotharius J, Brundin P (2002b) Impaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson's disease. Hum Mol Genet 11: 2395-2407.
115. Ma XC, Gottschall PE, Chen LT, Wiranowska M, Phelps CP (2002) Role and mechanisms of interleukin-1 in the modulation of neurotoxicity. Neuroimmunomodulation 10: 199-207.
116. Magistretti PJ, Ransom BR (2002) Astrocytes. In: Neuropsychoparmacology: The Fifth Generation of Progress (Charney DMD, Coyle JT, Nemeroff C, eds), Lippincott Williams & Wilkins (LWW) 133-145.
117. Maker HS, Weiss C, Silides DJ, Cohen G (1981) Coupling of dopamine oxidation (monoamine oxidase activity) to glutathione oxidation via the generation of hydrogen peroxide in rat brain homogenates. J Neurochem 36: 589-593.
118. Mamdani M, Rochon PA, Juurlink DN, Kopp A, Anderson GM, Naglie G, Austin PC, Laupacis A (2002) Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs. BMJ 325: 624.
119. Martin MU, Wesche H (2002) Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochim Biophys Acta 1592: 265-280.
120. Maruyama W, Strolin-Benedetti M, Naoi M (2000) N-methyl(R)salsolinol and a neutral N-methyltransferase as pathogenic factors in Parkinson's disease. Neurobiology (Bp) 8: 55-68.
121. Maslinska D, Wozniak R, Kaliszek A, Modelska I (1999) Expression of cyclooxygenase-2 in astrocytes of human brain after global ischemia. Folia Neuropathol 37: 75-79.
122. Matyszak MK (1998) Inflammation in the CNS: balance between immunological privilege and immune responses. Prog Neurobiol 56: 19-35.
123. McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 38: 1285-1291.
124. McGeer PL, McGeer EG (2004) Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism Relat Disord 10 (1): S3-S7.
125. McGeer PL, Schwab C, Parent A, Doudet D (2003) Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine administration. Ann Neurol 54: 599-604.
126. McNaught KS, Jenner P (2000) Extracellular accumulation of nitric oxide, hydrogen peroxide, and glutamate in astrocytic cultures following glutathione depletion, complex I inhibition, and/or lipopolysaccharide-induced activation. Biochem Pharmacol 60: 979-988.
127. McNaught KS, Olanow CW (2003) Proteolytic stress: a unifying concept for the etiopathogenesis of Parkinson's disease. Ann Neurol 53 Suppl 3: S73-S84.
128. Miklossy J, Doudet DD, Schwab C, Yu S, McGeer EG, McGeer PL (2006) Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys. Exp Neurol 197: 275-283.
129. Minghetti L (2004) Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol 63: 901-910.
130. Mirza B, Hadberg H, Thomsen P, Moos T (2000) The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson's disease. Neuroscience 95: 425-432.
131. Mogi M, Harada M, Kondo T, Riederer P, Inagaki H, Minami M, Nagatsu T (1994a) Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett 180: 147-150.
132. Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T (1994b) Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett 165: 208-210.
133. Mohanakumar KP, Muralikrishnan D, Thomas B (2000) Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced neurotoxicity. Brain Res 864: 281-290.
134. Morgan BP, Gasque P (1996) Expression of complement in the brain: role in health and disease. Immunol Today 17: 461-466.
135. Muller T, Blum-Degen D, Przuntek H, Kuhn W (1998) Interleukin-6 levels in cerebrospinal fluid inversely correlate to severity of Parkinson's disease. Acta Neurol Scand 98: 142-144.
136. Nakamura Y (2002) Regulating factors for microglial activation. Biol Pharm Bull 25: 945-953.
137. Nakayama M, Uchimura K, Zhu RL, Nagayama T, Rose ME, Stetler RA, Isakson PC, Chen J, Graham SH (1998) Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia. Proc Natl Acad Sci U S A 95: 10954-10959.
138. Norgard B, Pedersen L, Johnsen SP, Tarone RE, McLaughlin JK, Friis S, Sorensen HT (2004) COX-2-selective inhibitors and the risk of upper gastrointestinal bleeding in high-risk patients with previous gastrointestinal diseases: a population-based case-control study. Aliment Pharmacol Ther 19: 817-825.
139. O'Callaghan JP, Seidler FJ (1992) 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced astrogliosis does not require activation of ornithine decarboxylase. Neurosci Lett 148: 105-108.
140. Okuno T, Nakatsuji Y, Kumanogoh A, Moriya M, Ichinose H, Sumi H, Fujimura H, Kikutani H, Sakoda S (2005) Loss of dopaminergic neurons by the induction of inducible nitric oxide synthase and cyclooxygenase-2 via CD 40: relevance to Parkinson's disease. J Neurosci Res 81: 874-882.
141. Orr CF, Rowe DB, Mizuno Y, Mori H, Halliday GM (2005) A possible role for humoral immunity in the pathogenesis of Parkinson's disease. Brain 128: 2665-2674.
142. Orth M, Schapira AH (2002) Mitochondrial involvement in Parkinson's disease. Neurochem Int 40: 533-541.
143. Osterud B, Bjorklid E (2003) Role of monocytes in atherogenesis. Physiol Rev 83: 1069-1112.
144. Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, Torizuka T (2005) Microglial activation and dopamine terminal loss in early Parkinson's disease. Ann Neurol 57: 168-175.
145. Pakkenberg B, Moller A, Gundersen HJ, Mouritzen DA, Pakkenberg H (1991) The absolute number of nerve cells in substantia nigra in normal subjects and in patients with Parkinson's disease estimated with an unbiased stereological method. J Neurol Neurosurg Psychiatry 54: 30-33.
146. Patrignani P, Tacconelli S, Sciulli MG, Capone ML (2005) New insights into COX-2 biology and inhibition. Brain Res Brain Res Rev 48: 352-359.
147. Pearce RK, Owen A, Daniel S, Jenner P, Marsden CD (1997) Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease. J Neural Transm 104: 661-677.
148. Pellerin L (2005) How astrocytes feed hungry neurons. Mol Neurobiol 32: 59-72.
149. Possel H, Noack H, Putzke J, Wolf G, Sies H (2000) Selective upregulation of inducible nitric oxide synthase (iNOS) by lipopolysaccharide (LPS) and cytokines in microglia: in vitro and in vivo studies. Glia 32: 51-59.
150. Przybylkowski A, Kurkowska-Jastrzebska I, Joniec I, Ciesielska A, Czlonkowska A, Czlonkowski A (2004) Cyclooxygenases mRNA and protein expression in striata in the experimental mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine administration to mouse. Brain Res 1019: 144-151.
151. Reinhard JF Jr, Miller DB, O'Callaghan JP (1988) The neurotoxicant MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) increases glial fibrillary acidic protein and decreases dopamine levels of the mouse striatum: evidence for glial response to injury. Neurosci Lett 95: 246-251.
152. Roth GJ, Stanford N, Majerus PW (1975) Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci U S A 72: 3073-3076.
153. Rousselet E, Callebert J, Parain K, Joubert C, Hunot S, Hartmann A, Jacque C, Perez-Diaz F, Cohen-Salmon C, Launay JM, Hirsch EC (2002) Role of TNF-alpha receptors in mice intoxicated with the parkinsonian toxin MPTP. Exp Neurol 177: 183-192.
154. Rowe DB, Le W, Smith RG, Appel SH (1998) Antibodies from patients with Parkinson's disease react with protein modified by dopamine oxidation. J Neurosci Res 53: 551-558.
155. Sanchez-Pernaute R, Ferree A, Cooper O, Yu M, Brownell AL, Isacson O (2004) Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease. J Neuroinflammation 1: 6.
156. Scali C, Giovannini MG, Prosperi C, Bellucci A, Pepeu G, Casamenti F (2003) The selective cyclooxygenase-2 inhibitor rofecoxib suppresses brain inflammation and protects cholinergic neurons from excitotoxic degeneration in vivo. Neuroscience 117: 909-919.
157. Scatton B, Rouquier L, Javoy-Agid F, Agid Y (1982) Dopamine deficiency in the cerebral cortex in Parkinson disease. Neurology 32: 1039-1040.
158. Schapira AH (1994) Evidence for mitochondrial dysfunction in Parkinson's disease-a critical appraisal. Mov Disord 9: 125-138.
159. Schipper HM, Liberman A, Stopa EG (1998) Neural heme oxygenase-1 expression in idiopathic Parkinson's disease. Exp Neurol 150: 60-68.
160. Schneider JS, Denaro FJ (1988) Astrocytic responses to the dopaminergic neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in cat and mouse brain. J Neuropathol Exp Neurol 47: 452-458.
161. Schnitzer TJ, Burmester GR, Mysler E, Hochberg MC, Doherty M, Ehrsam E, Gitton X, Krammer G, Mellein B, Matchaba P, Gimona A, Hawkey CJ (2004) Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet 364: 665-674.
162. Selmaj KW, Farooq M, Norton WT, Raine CS, Brosnan CF (1990) Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J Immunol 144: 129-135.
163. Sheng JG, Shirabe S, Nishiyama N, Schwartz JP (1993) Alterations in striatal glial fibrillary acidic protein expression in response to 6-hydroxydopamine-induced denervation. Exp Brain Res 95: 450-456.
164. Sherer TB, Betarbet R, Greenamyre JT (2002) Environment, mitochondria, and Parkinson's disease. Neuroscientist 8: 192-197.
165. Sherer TB, Betarbet R, Kim JH, Greenamyre JT (2003) Selective microglial activation in the rat rotenone model of Parkinson's disease. Neurosci Lett 341: 87-90.
166. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS (2000) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 284: 1247-1255.
167. Simard M, Nedergaard M (2004) The neurobiology of glia in the context of water and ion homeostasis. Neuroscience 129: 877-896.
168. Singhrao SK, Neal JW, Rushmere NK, Morgan BP, Gasque P (2000) Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis. Am J Pathol 157: 905-918.
169. Smith WL, Garavito RM, DeWittDL(1996) Prostaglandin endoperoxideHsynthases (cyclooxygenases)-1 and-2. J Biol Chem 271: 33157-33160.
170. Sofic E, Lange KW, Jellinger K, Riederer P (1992) Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. Neurosci Lett 142: 128-130.
171. Sofic E, Riederer P, Heinsen H, Beckmann H, Reynolds GP, Hebenstreit G, Youdim MB (1988) Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J Neural Transm 74: 199-205.
172. Sofroniew MV (2005) Reactive astrocytes in neural repair and protection. Neuroscientist 11: 400-407.
173. Spencer JP, Jenner P, Daniel SE, Lees AJ, Marsden DC, Halliwell B (1998) Conjugates of catecholamines with cysteine and GSH in Parkinson's disease: possible mechanisms of formation involving reactive oxygen species. J Neurochem 71: 2112-2122.
174. Sriram K, Miller DB, O'Callaghan JP (2006) Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-alpha. J Neurochem 96: 706-718.
175. Stokes AH, Hastings TG, Vrana KE (1999) Cytotoxic and genotoxic potential of dopamine. J Neurosci Res 55: 659-665.
176. Stromberg I, Bjorklund H, Dahl D, Jonsson G, Sundstrom E, Olson L (1986) Astrocyte responses to dopaminergic denervations by 6-hydroxydopamine and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine as evidenced by glial fibrillary acidic protein immunohistochemistry. Brain Res Bull 17: 225-236.
177. Sudo S, Tanaka J, Toku K, Desaki J, Matsuda S, Arai T, Sakanaka M, Maeda N (1998) Neurons induce the activation of microglial cells in vitro. Exp Neurol 154: 499-510.
178. Sulzer D, Zecca L (2000) Intraneuronal dopamine-quinone synthesis: a review. Neurotox Res 1: 181-195.
179. Taylor DL, Diemel LT, Pocock JM (2003) Activation of microglial group III metabotropic glutamate receptors protects neurons against microglial neurotoxicity. J Neurosci 23: 2150-2160.
180. Teismann P, Ferger B (2001) Inhibition of the cyclooxygenase isoenzymes COX-1 and COX-2 provide neuroprotection in the MPTP-mouse model of Parkinson's disease. Synapse 39: 167-174.
181. Teismann P, Tieu K, Choi DK, Wu DC, Naini A, Hunot S, Vila M, Jackson-Lewis V, Przedborski S (2003) Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc Natl Acad Sci U S A 100: 5473-5478.
182. Thomas M, Le WD (2004) Minocycline: neuroprotective mechanisms in Parkinson's disease. Curr Pharm Des 10: 679-686.
183. Tse DC, McCreery RL, Adams RN (1976) Potential oxidative pathways of brain catecholamines. J Med Chem 19: 37-40.
184. van Beek J, Elward K, Gasque P (2003) Activation of complement in the central nervous system: roles in neurodegeneration and neuroprotection. Ann N Y Acad Sci 992: 56-71.
185. van Beek J, van MM, 't Hart BA, Brok HP, Neal JW, Chatagner A, Harris CL, Omidvar N, Morgan BP, Laman JD, Gasque P (2005) Decay-accelerating factor (CD55) is expressed by neurons in response to chronic but not acute autoimmune central nervous system inflammation associated with complement activation. J Immunol 174: 2353-2365.
186. van der Goes A, Kortekaas M, Hoekstra K, Dijkstra CD, Amor S (1999) The role of anti-myelin (auto)-antibodies in the phagocytosis of myelin by macrophages. J Neuroimmunol 101: 61-67.
187. Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 231: 232-235.
188. Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6: 626-640.
189. Walker MC, Kurumbail RG, Kiefer JR, Moreland KT, Koboldt CM, Isakson PC, Seibert K, Gierse JK (2001) A three-step kinetic mechanism for selective inhibition of cyclo-oxygenase-2 by diarylheterocyclic inhibitors. Biochem J 357: 709-718.
190. Wang MJ, Lin WW, Chen HL, Chang YH, Ou HC, Kuo JS, Hong JS, Jeng KC (2002) Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation. Eur J Neurosci 16: 2103-2112.
191. Wang T, Pei Z, Zhang W, Liu B, Langenbach R, Lee C, Wilson B, Reece JM, Miller DS, Hong JS (2005) MPP+-induced COX-2 activation and subsequent dopaminergic neurodegeneration. FASEB J 19: 1134-1136.
192. Warner TD, Mitchell JA (2004) Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J 18: 790-804.
193. Willard LB, Hauss-Wegrzyniak B, Danysz W, Wenk GL (2000) The cytotoxicity of chronic neuroinflammation upon basal forebrain cholinergic neurons of rats can be attenuated by glutamatergic antagonism or cyclooxygenase-2 inhibition. Exp Brain Res 134: 58-65.
194. Wilms H, Rosenstiel P, Sievers J, Deuschl G, Zecca L, Lucius R (2003) Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson's disease. FASEB J 17: 500-502.
195. Xu J, Chalimoniuk M, Shu Y, Simonyi A, Sun AY, Gonzalez FA, Weisman GA, Wood WG, Sun GY (2003) Prostaglandin E2 production in astrocytes: regulation by cytokines, extracellular ATP, and oxidative agents. Prostaglandins Leukot Essent Fatty Acids 69: 437-448.
196. Yamada T, McGeer PL, McGeer EG (1992) Lewy bodies in Parkinson's disease are recognized by antibodies to complement proteins. Acta Neuropathol (Berl) 84: 100-104.
197. Yamamoto K, Arakawa T, Ueda N, Yamamoto S (1995) Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells. J Biol Chem 270: 31315-31320.
198. Yermakova AV, O'Banion MK (2001) Downregulation of neuronal cyclooxygenase-2 expression in end stage Alzheimer's disease. Neurobiol Aging 22: 823-836.
199. Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci U S A 93: 2696-2701.
200. Zassler B, Weis C, Humpel C (2003) Tumor necrosis factor-alpha triggers cell death of sensitized potassium chloride-stimulated cholinergic neurons. Brain Res Mol Brain Res 113: 78-85.
201. Zhang J, Perry G, Smith MA, Robertson D, Olson SJ, Graham DG, Montine TJ (1999) Parkinson's disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol 154: 1423-1429.
202. Zimprich A, et al. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44: 601-607.