Insights into neuroinflammation in Parkinson's disease: From biomarkers to anti-inflammatory based therapies

BioMed Research International

Volumn 2015, Issue , 2015, Pages

  Rocha, Natália Pessoa ^a   De Miranda, Aline Silva ^a   Teixeira, Antônio Lúcio ^a  

^a FEDERAL UNIVERSITY OF MINAS GERAIS   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; ANTIINFLAMMATORY AGENT; ANTIPARKINSON AGENT; BCG VACCINE; BIOLOGICAL MARKER; CD4 ANTIGEN; CD8 ANTIGEN; EOTAXIN; EOTAXIN 2; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 15; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 8; LEUCINE RICH REPEAT KINASE 2; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE MIGRATION INHIBITION FACTOR; MONOCYTE CHEMOTACTIC PROTEIN 1; NONSTEROID ANTIINFLAMMATORY AGENT; RANTES; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR 2;

AUTOIMMUNITY; AUTOPSY; BCG VACCINATION; CD4+ T LYMPHOCYTE; CELL ACTIVATION; CENTRAL NERVOUS SYSTEM; DRUG USE; GENETIC ASSOCIATION; HUMAN; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IMMUNOSTIMULATION; IMMUNOTHERAPY; MICROGLIA; NERVOUS SYSTEM INFLAMMATION; NEUROIMAGING; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PERIPHERAL NERVOUS SYSTEM; POSITRON EMISSION TOMOGRAPHY; PROGNOSIS; REVIEW; ANIMAL; COMPLICATION; DRUG EFFECTS; GENETICS; GENOME-WIDE ASSOCIATION STUDY; IMMUNOLOGY; INFLAMMATION; METABOLISM; NERVOUS SYSTEM; PATHOLOGY;

ANIMALS; ANTI-INFLAMMATORY AGENTS; BIOMARKERS; GENOME-WIDE ASSOCIATION STUDY; HUMANS; INFLAMMATION; NERVOUS SYSTEM; PARKINSON DISEASE;

EID: 84939208750     PISSN: 23146133     EISSN: 23146141     Source Type: Journal    
DOI: 10.1155/2015/628192     Document Type: Review

References (114)

1. A. Samii, J. G. Nutt, and B. R. Ransom, "Parkinsons disease," The Lancet, vol. 363, no. 9423, pp. 1783-1793, 2004.
2. A. J. Hughes, S. E. Daniel, L. Kilford, and A. J. Lees, "Accuracy of clinical diagnosis of idiopathic Parkinsons disease: a clinicopathological study of 100 cases," Journal of Neurology Neurosurgery and Psychiatry, vol. 55, no. 3, pp. 181-184, 1992.
3. M. B. Stern, A. Lang, and W. Poewe, "Toward a redefinition of Parkinsons disease," Movement Disorders, vol. 27, no. 1, pp. 54-60, 2012.
4. J. Parkinson, "An essay on the shaking palsy," The Journal of Neuropsychiatry and Clinical Neurosciences, vol. 14, no. 2, pp. 223-236, 2002.
5. K. A. Jellinger, "Neuropathology of sporadic Parkinsons disease: evaluation and changes of concepts," Movement Disorders, vol. 27, no. 1, pp. 8-30, 2012.
6. T. Pringsheim, N. Jette, A. Frolkis, and T. D. L. Steeves, "The prevalence of Parkinsons disease: a systematic reviewandmetaanalysis," Movement Disorders, vol. 29, no. 13, pp. 1583-1590, 2014.
7. T. Pringsheim, K. Fiest, and N. Jette, "The international incidence and prevalence of neurologic conditions: how common are they?" Neurology, vol. 83, no. 18, pp. 1661-1664, 2014.
8. B. S. Connolly and A. E. Lang, "Pharmacological treatment of Parkinson disease: a review," Journal of the American Medical Association, vol. 311, no. 16, pp. 1670-1683, 2014.
9. P. L. McGeer, S. Itagaki, B. E. Boyes, and E. G. McGeer, "Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinsons and Alzheimers disease brains," Neurology, vol. 38, no. 8, pp. 1285-1291, 1988.
10. H.-M. Gao and J.-S. Hong, "Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression," Trends in Immunology, vol. 29, no. 8, pp. 357-365, 2008.
11. L. M. Collins, A. Toulouse, T. J. Connor, and Y. M. Nolan, "Contributions of central and systemic inflammation to the pathophysiology of Parkinsons disease," Neuropharmacology, vol. 62, no. 7, pp. 2154-2168, 2012.
12. R. B. Banati, S. E. Daniel, and S. B. Blunt, "Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinsons disease," Movement Disorders, vol. 13, no. 2, pp. 221-227, 1998.
13. K. Imamura, N. Hishikawa, M. Sawada, T. Nagatsu, M. Yoshida, and Y. Hashizume, "Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinsons disease brains," Acta Neuropathologica, vol. 106, no. 6, pp. 518-526, 2003.
14. B. Mirza, H. Hadberg, P. Thomsen, and T. Moos, "The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinsons disease," Neuroscience, vol. 95, no. 2, pp. 425-432, 1999.
15. A. D. Reynolds, J. G. Glanzer, I. Kadiu et al., "Nitrated alphasynuclein- activated microglial profiling for Parkinsons disease," Journal of Neurochemistry, vol. 104, no. 6, pp. 1504-1525, 2008.
16. C. Knott, G. Stern, and G. P. Wilkin, "Inflammatory regulators in Parkinsons disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2,"Molecular and CellularNeuroscience, vol. 16, no. 6, pp. 724-739, 2000.
17. M. K. McCoy, T. N. Martinez, K. A. Ruhn et al., "Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinsons disease," Journal of Neuroscience, vol. 26, no. 37, pp. 9365-9375, 2006.
18. M. Shimoji, F. Pagan, E. B. Healton, and I. Mocchetti, "CXCR4 and CXCL12 expression is increased in the nigro-striatal system of Parkinsons disease," Neurotoxicity Research, vol. 16, no. 3, pp. 318-328, 2009.
19. A. Bachis, S. A. Aden, R. L. Nosheny, P. M. Andrews, and I. Mocchetti, "Axonal transport of human immunodeficiency virus type 1 envelope protein glycoprotein 120 is found in association with neuronal apoptosis," Journal of Neuroscience, vol. 26, no. 25, pp. 6771-6780, 2006.
20. S. Hunot, F. Boissiere, B. Faucheux et al., "Nitric oxide synthase and neuronal vulnerability in Parkinsons disease," Neuroscience, vol. 72, no. 2, pp. 355-363, 1996.
21. P. L. McGeer, K. Yasojima, and E. G. McGeer, "Association of interleukin-1β polymorphisms with idiopathic Parkinsons disease," Neuroscience Letters, vol. 326, no. 1, pp. 67-69, 2002.
22. R. Kruger, C. Hardt, F. Tschentscher et al., "Genetic analysis of immunomodulating factors in sporadic Parkinsons disease," Journal ofNeural Transmission, vol. 107, no. 5, pp. 553-562, 2000.
23. A. Hakansson, L. Westberg, S. Nilsson et al., "Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinsons disease," The American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, vol. 133, no. 1, pp. 88-92, 2005.
24. A. D. Wahner, J. S. Sinsheimer, J. M. Bronstein, and B. Ritz, "Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease," Archives of Neurology, vol. 64, no. 6, pp. 836-840, 2007.
25. M. Mogi, A. Togari, T. Kondo et al., "Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra fromParkinsonian brain," Journal of Neural Transmission, vol. 107, no. 3, pp. 335-341, 2000.
26. A. L. D. L. Ezcurra, M. Chertoff, C. Ferrari, M. Graciarena, and F. Pitossi, "Chronic expression of low levels of tumor necrosis factor-α in the substantia nigra elicits progressive neurodegeneration, delayed motor symptoms and microglia/macrophage activation," Neurobiology of Disease, vol. 37, no. 3, pp. 630-640, 2010.
27. C. C. Ferrari, M. C. Pott Godoy, R. Tarelli, M. Chertoff, A. M. Depino, and F. J. Pitossi, "Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra," Neurobiology of Disease, vol. 24, no. 1, pp. 183-193, 2006.
28. P. Garcia-Esparcia, F. Llorens, M. Carmona, and I. Ferrer, "Complex deregulation and expression of cytokines and mediators of the immune response in parkinsons disease brain is region dependent," Brain Pathology, vol. 24, no. 6, pp. 584-598, 2014.
29. M. Shi, J. Bradner, A. M. Hancock et al., "Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression," Annals of Neurology, vol. 69, no. 3, pp. 570-580, 2011.
30. D. Blum-Degena, T. Muller, W. Kuhn, M. Gerlach, H. Przuntek, and P. Riederer, "Interleukin-1β and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimers and de novo Parkinsons disease patients," Neuroscience Letters, vol. 202, no. 1-2, pp. 17-20, 1995.
31. M. Mogi, M. Harada, H. Narabayashi, H. Inagaki, M. Minami, and T. Nagatsu, "Interleukin (IL)-1β, IL-2, IL-4, IL-6 and transforming growth factor-α levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinsons disease," Neuroscience Letters, vol. 211, no. 1, pp. 13-16, 1996.
32. M. P. Vawter, O. Dillon-Carter, W. W. Tourtellotte, P. Carvey, and W. J. Freed, "TGFβ1 andTGFβ2 concentrations are elevated in Parkinsons disease in ventricular cerebrospinal fluid," Experimental Neurology, vol. 142, no. 2, pp. 313-322, 1996.
33. D. Lindqvist, S. Hall, Y. Surova et al., "Cerebrospinal fluid inflammatory markers in Parkinsons disease-associations with depression, fatigue, and cognitive impairment," Brain, Behavior, and Immunity, vol. 33, pp. 183-189, 2013.
34. E. Bezard, Z. Yue, D. Kirik, and M. G. Spillantini, "Animal models of Parkinsons disease: limits and relevance to neuroprotection studies," Movement Disorders, vol. 28, no. 1, pp. 61-70, 2013.
35. F. M. Ribeiro, E. R. D. S. Camargos, L. C. de Souza, and A. L. Teixeira, "Animal models of neurodegenerative diseases," Revista Brasileira de Psiquiatria, vol. 35, supplement 2, pp. S82- S91, 2013.
36. D. Trabzuni, M. Ryten, W. Emmett et al., "Fine-mapping, gene expression and splicing analysis of the disease associated LRRK2 locus," PLoS ONE, vol. 8, no. 8, Article ID e70724, 2013.
37. J. Thevenet, R. Gobert, R. H. van Huijsduijnen, C. Wiessner, and Y. J. Sagot, "Regulation of LRRK2 expression points to a functional role in human monocyte maturation," PLoS ONE, vol. 6, no. 6, Article ID e21519, 2011.
38. M. S. Moehle, P. J. Webber, T. Tse et al., "LRRK2 inhibition attenuates microglial inflammatory responses," The Journal of Neuroscience, vol. 32, no. 5, pp. 1602-1611, 2012.
39. J. P. Daher, L. A. Volpicelli-Daley, J. P. Blackburn, M. S. Moehle, and A. B. West, "Abrogation of α-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats," Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 25, pp. 9289-9294, 2014.
40. R. B. Banati, J. Newcombe, R. N. Gunn et al., "The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as ameasure of disease activity," Brain, vol. 123, no. 11, pp. 2321-2337, 2000.
41. F. Dolle, C. Luus, A. Reynolds, and M. Kassiou, "Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography," Current Medicinal Chemistry, vol. 16, no. 22, pp. 2899-2923, 2009.
42. Y. Ouchi, E. Yoshikawa, Y. Sekine et al., "Microglial activation and dopamine terminal loss in early Parkinsons disease," Annals of Neurology, vol. 57, no. 2, pp. 168-175, 2005.
43. A. Gerhard, N. Pavese, G. Hotton et al., "In vivo imaging of microglial activation with 11C](R)-PK11195 PET in idiopathic Parkinsons disease," Neurobiology of Disease, vol. 21, no. 2, pp. 404-412, 2006.
44. Y. Ouchi, S. Yagi, M. Yokokura, and M. Sakamoto, "Neuroinflammation in the living brain of Parkinsons disease," Parkinsonism and Related Disorders, vol. 15, supplement 3, pp. S200-S204, 2009.
45. A. L. Bartels, A. T. M. Willemsen, J. Doorduin, E. F. J. de Vries, R. A. Dierckx, and K. L. Leenders, "11C]-PK11195 PET: quantification of neuroinflammation and a monitor of antiinflammatory treatment in Parkinsons disease?" Parkinsonism and Related Disorders, vol. 16, no. 1, pp. 57-59, 2010.
46. R. Sanchez-Pernaute, A. Ferree, O. Cooper, M. Yu, A.-L. Brownell, and O. Isacson, "Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinsons disease," Journal ofNeuroinflammation, vol. 1, article 6, 2004.
47. P. Edison, I. Ahmed, Z. Fan et al., "Microglia, amyloid, and glucose metabolism in Parkinsons disease with and without dementia," Neuropsychopharmacology, vol. 38, no. 6, pp. 938-949, 2013.
48. D. Koziorowski, R. Tomasiuk, S. Szlufik, and A. Friedman, "Inflammatory cytokines and NT-proCNP in Parkinsons disease patients," Cytokine, vol. 60, no. 3, pp. 762-766, 2012.
49. R. J. Dobbs, A. Charlett, A. G. Purkiss, S. M. Dobbs, C. Weller, and D. W. Peterson, "Association of circulating TNF-α and IL-6 with ageing and parkinsonism," Acta Neurologica Scandinavica, vol. 100, no. 1, pp. 34-41, 1999.
50. P. Scalzo, A. Kummer, F. Cardoso, and A. L. Teixeira, "Increased serum levels of soluble tumor necrosis factor-α receptor-1 in patients with Parkinsons disease," Journal of Neuroimmunology, vol. 216, no. 1-2, pp. 122-125, 2009.
51. N. P. Rocha, A. L. Teixeira, P. L. Scalzo et al., "Plasma levels of soluble tumor necrosis factor receptors are associated with cognitive performance in Parkinsons disease," Movement Disorders, vol. 29, no. 4, pp. 527-531, 2014.
52. Z. Katsarou, S. Bostantjopoulou, O. Hatzizisi, E. Giza, A. Soler- Cardona, and G. Kyriazis, "Immune factors or depression? Fatigue correlates in Parkinsons disease," Revista de Neurologia, vol. 45, no. 12, pp. 725-728, 2007.
53. A. Nicoletti, P. Fagone, G. Donzuso et al., "Parkinsons disease is associated with increased serum levels of macrophage migration inhibitory factor," Cytokine, vol. 55, no. 2, pp. 165-167, 2011.
54. B. Brodacki, J. Staszewski, B. Toczylowska et al., "Serum interleukin (IL-2, IL-10, IL-6, IL-4), TNFα, and INFγ concentrations are elevated in patients with atypical and idiopathic parkinsonism," Neuroscience Letters, vol. 441, no. 2, pp. 158-162, 2008.
55. G. Stypula, J. Kunert-Radek, H. Stepien, K. Zylinska, and M. Pawlikowski, "Evaluation of interleukins, ACTH, cortisol and prolactin concentrations in the blood of patients with Parkinsons disease," NeuroImmunoModulation, vol. 3, no. 2-3, pp. 131-134, 1996.
56. D. Lindqvist, E. Kaufman, L. Brundin, S. Hall, Y. Surova, and O. Hansson, "Non-motor symptoms in patients with Parkinsons disease-correlations with inflammatory cytokines in serum," PLoS ONE, vol. 7, no. 10, Article IDe47387, 2012.
57. P. Scalzo, A. Kummer, F. Cardoso, and A. L. Teixeira, "Serum levels of interleukin-6 are elevated in patients with Parkinsons disease and correlate with physical performance," Neuroscience Letters, vol. 468, no. 1, pp. 56-58, 2010.
58. H. Chen, E. J. OReilly, M. A. Schwarzschild, and A. Ascherio, "Peripheral inflammatory biomarkers and risk of Parkinsons disease," American Journal of Epidemiology, vol. 167, no. 1, pp. 90-95, 2008.
59. K. W. Hofmann, A. F. S. Schuh, J. Saute et al., "Interleukin-6 serum levels in patients with parkinsons disease," Neurochemical Research, vol. 34, no. 8, pp. 1401-1404, 2009.
60. M. Dufek, M. Hamanova, J. Lokaj et al., "Serum inflammatory biomarkers in Parkinsons disease," Parkinsonism and Related Disorders, vol. 15, no. 4, pp. 318-320, 2009.
61. T. Mihara, M. Nakashima, A. Kuroiwa et al., "Natural killer cells of Parkinsons disease patients are set up for activation: a possible role for innate immunity in the pathogenesis of this disease," Parkinsonism and Related Disorders, vol. 14, no. 1, pp. 46-51, 2008.
62. M. Rentzos, C. Nikolaou, E. Andreadou et al., "Circulating interleukin-10 and interleukin-12 in Parkinsons disease," Acta Neurologica Scandinavica, vol. 119, no. 5, pp. 332-337, 2009.
63. P. Scalzo, A. S. De Miranda, D. C. Guerra Amaral, M. De Carvalho Vilela, F. Cardoso, and A. L. Teixeira, "Serumlevels of chemokines in Parkinsons disease," NeuroImmunoModulation, vol. 18, no. 4, pp. 240-244, 2011.
64. N. P. Rocha, P. L. Scalzo, I. G. Barbosa et al., "Cognitive status correlates with CXCL10/IP-10 levels in Parkinsons disease," Parkinsons Disease, vol. 2014, Article ID 903796, 7 pages, 2014.
65. M. Reale, C. Iarlori, A. Thomas et al., "Peripheral cytokines profile in Parkinsons disease," Brain, Behavior, and Immunity, vol. 23, no. 1, pp. 55-63, 2009.
66. H. Kluter, P. Vieregge, H. Stolze, and H. Kirchner, "Defective production of interleukin-2 in patients with idiopathic Parkinsons disease," Journal of the Neurological Sciences, vol. 133, no. 1-2, pp. 134-139, 1995.
67. M. Malaguarnera, A. Laurino, I. di Fazio et al., "Neuropsychiatric effects and type of IFN-α in chronic hepatitis C," Journal of Interferon and Cytokine Research, vol. 21, no. 5, pp. 273-278, 2001.
68. N. Atasoy, Y. Ustundag, N. Konuk, and L. Atik, "Acute dystonia during pegylated interferon alpha therapy in a casewith chronic hepatitis B infection," ClinicalNeuropharmacology, vol. 27, no. 3, pp. 105-107, 2004.
69. M. Kajihara, S. Montagnese, P. Khanna et al., "Parkinsonism in patients with chronic hepatitis C treated with interferon-α2b: a report of two cases," European Journal of Gastroenterology and Hepatology, vol. 22, no. 5, pp. 628-631, 2010.
70. M. A. Harris, J. K. Tsui, S. A. Marion, H. Shen, and K. Teschke, "Association of Parkinsons disease with infections and occupational exposure to possible vectors," Movement Disorders, vol. 27, no. 9, pp. 1111-1117, 2012.
71. J. Bas, M. Calopa, M. Mestre et al., "Lymphocyte populations in Parkinsons disease and in rat models of parkinsonism," Journal of Neuroimmunology, vol. 113, no. 1, pp. 146-152, 2001.
72. Y. Baba, A. Kuroiwa, R. J. Uitti, Z. K. Wszolek, and T. Yamada, "Alterations of T-lymphocyte populations in Parkinson disease," Parkinsonism and Related Disorders, vol. 11, no. 8, pp. 493-498, 2005.
73. J. A. H. Saunders, K. A. Estes, L. M. Kosloski et al., "CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinsons disease," Journal of Neuroimmune Pharmacology, vol. 7, no. 4, pp. 927-938, 2012.
74. C. H. Stevens, D. Rowe, M.-C. Morel-Kopp et al., "Reduced T helper and B lymphocytes in Parkinsons disease," Journal of Neuroimmunology, vol. 252, no. 1-2, pp. 95-99, 2012.
75. M. Calopa, J. Bas, A. Callen, and M. Mestre, "Apoptosis of peripheral blood lymphocytes in Parkinson patients," Neurobiology of Disease, vol. 38, no. 1, pp. 1-7, 2010.
76. A. Prigione, I. U. Isaias, A. Galbussera et al., "Increased oxidative stress in lymphocytes from untreated Parkinsons disease patients," Parkinsonism and Related Disorders, vol. 15, no. 4, pp. 327-328, 2009.
77. F. Niwa, N. Kuriyama, M. Nakagawa, and J. Imanishi, "Effects of peripheral lymphocyte subpopulations and the clinical correlation with Parkinsons disease," Geriatrics and Gerontology International, vol. 12, no. 1, pp. 102-107, 2012.
78. P. L. McGeer and E. G. McGeer, "Inflammation and the degenerative diseases of aging," Annals of theNewYork Academy of Sciences, vol. 1035, pp. 104-116, 2004.
79. T. H. Hamza, C. P. Zabetian, A. Tenesa et al., "Common genetic variation in the HLA region is associated with late-onset sporadic Parkinsons disease," Nature Genetics, vol. 42, no. 9, pp. 781-785, 2010.
80. J. Simon-Sanchez, J. J. van Hilten, B. van de Warrenburg et al., "Genome-wide association study confirms extant PD risk loci among the Dutch," European Journal of Human Genetics, vol. 19, no. 6, pp. 655-661, 2011.
81. S. J. Chung, S. M. Armasu, J. M. Biernacka et al., "Genomic determinants of motor and cognitive outcomes in Parkinsons disease," Parkinsonism and Related Disorders, vol. 18, no. 7, pp. 881-886, 2012.
82. M. A. Nalls, N. Pankratz, C. M. Lill et al., "Large-scale metaanalysis of genome-wide association data identifies six new risk loci for Parkinsons disease," Nature Genetics, vol. 46, no. 9, pp. 989-993, 2014.
83. E. K. Tan, "Genetic marker linking inflammation with sporadic Parkinsons disease," Annals of the Academy of Medicine Singapore, vol. 40, no. 2, pp. 111-112, 2011.
84. G. G. Tribl, C. Wober, V. Schonborn, T. Brucke, L. Deecke, and S. Panzer, "Amantadine in Parkinsons disease: lymphocyte subsets and IL-2 secreting T cell precursor frequencies," Experimental Gerontology, vol. 36, no. 10, pp. 1761-1771, 2001.
85. H. Kluter, P. Vieregge, H. Stolze, and H. Kirchner, "Defective production of interleukin-2 in patients with idiopathic Parkinsons disease," Journal of the Neurological Sciences, vol. 133, no. 1-2, pp. 134-139, 1995.
86. K. P. Wandinger, J. M. Hagenah, H. Kluter, M. Rothermundt, M. Peters, and P. Vieregge, "Effects of amantadine treatment on in vitro production of interleukin-2 in de-novo patients with idiopathic Parkinsons disease," Journal of Neuroimmunology, vol. 98, no. 2, pp. 214-220, 1999.
87. T. Alberio, A. C. Pippione, C. Comi et al., "Dopaminergic therapies modulate the T-CELL proteome of patients with Parkinsons disease," IUBMB Life, vol. 64, no. 10, pp. 846-852, 2012.
88. S. Gangemi, G. Basile, R. A. Merendino et al., "Effect of levodopa on interleukin-15 and RANTES circulating levels in patients affected by Parkinsons disease," Mediators of Inflammation, vol. 12, no. 4, pp. 251-253, 2003.
89. H. Bessler, R. Djaldetti, H. Salman, M. Bergman, and M. Djaldetti, "IL-1β, IL-2, IL-6 and TNF-α production by peripheral blood mononuclear cells from patients with Parkinsons disease," Biomedicine and Pharmacotherapy, vol. 53, no. 3, pp. 141-145, 1999.
90. H. Chen, S. M. Zhang, M. A. Hernan et al., "Nonsteroidal antiinflammatory drugs and the risk of Parkinson disease," Archives of Neurology, vol. 60, no. 8, pp. 1059-1064, 2003.
91. H. Chen, E. Jacobs, M. A. Schwarzschild et al., "Nonsteroidal antiinflammatory drug use and the risk for Parkinsons disease," Annals of Neurology, vol. 58, no. 6, pp. 963-967, 2005.
92. X. Gao, H. Chen, M. A. Schwarzschild, and A. Ascherio, "Use of ibuprofen and risk of Parkinson disease," Neurology, vol. 76, no. 10, pp. 863-869, 2011.
93. D. Casper, U. Yaparpalvi, N. Rempel, and P. Werner, "Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro," Neuroscience Letters, vol. 289, no. 3, pp. 201-204, 2000.
94. A. D. Wahner, J. M. Bronstein, Y. M. Bordelon, and B. Ritz, "Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease," Neurology, vol. 69, no. 19, pp. 1836-1842, 2007.
95. K. M. Powers, D. M. Kay, S. A. Factor et al., "Combined effects of smoking, coffee, and NSAIDs on Parkinsons disease risk," Movement Disorders, vol. 23, no. 1, pp. 88-95, 2008.
96. T. G. Ton, S. R. Heckbert, W. T. Longstreth Jr. et al., "Nonsteroidal anti-inflammatory drugs and risk of Parkinsons disease," Movement Disorders, vol. 21, no. 7, pp. 964-969, 2006.
97. D. B. Hancock, E. R. Martin, J. M. Stajich et al., "Smoking, caffeine, and nonsteroidal anti-inflammatory drugs in families with Parkinson disease," Archives of Neurology, vol. 64, no. 4, pp. 576-580, 2007.
98. M. Bornebroek, L. M. L. De Lau, M. D. M. Haag et al., "Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease," Neuroepidemiology, vol. 28, no. 4, pp. 193-196, 2007.
99. M. Etminan, B. C. Carleton, and A. Samii, "Non-steroidal antiinflammatory drug use and the risk of Parkinson disease: a retrospective cohort study," Journal of ClinicalNeuroscience, vol. 15, no. 5, pp. 576-577, 2008.
100. J. A. Driver, G. Logroscino, L. Lu, J. M. Gaziano, and T. Kurth, "Use of non-steroidal anti-inflammatory drugs and risk of Parkinsons disease: nested case-control study," British Medical Journal, vol. 342, no. 7791, article d198, p. 270, 2011.
101. A. D. Manthripragada, E. S. Schernhammer, J. Qiu et al., "Nonsteroidal anti-inflammatory drug use and the risk of Parkinsons disease," Neuroepidemiology, vol. 36, no. 3, pp. 155-161, 2011.
102. C. Becker, S. S. Jick, and C. R. Meier, "NSAID use and risk of Parkinson disease: a population-based case-control study," European Journal of Neurology, vol. 18, no. 11, pp. 1336-1342, 2011.
103. A. Samii, M. Etminan, M. O. Wiens, and S. Jafari, "NSAID use and the risk of parkinsons disease: systematic review andmetaanalysis of observational studies," Drugs and Aging, vol. 26, no. 9, pp. 769-779, 2009.
104. J. J. Gagne and M. C. Power, "Anti-inflammatory drugs and risk of Parkinson disease: ameta-analysis," Neurology, vol. 74, no. 12, pp. 995-1002, 2010.
105. F. LEpiscopo, C. Tirolo, S. Caniglia et al., "Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine model of Parkinsons disease," Journal of Neuroinflammation, vol. 7, article 83, 2010.
106. J. M. Garcia-Moreno and J. Chacon, "Juvenile parkinsonism as a manifestation of systemic lupus erythematosus: case report and review of the literature," Movement Disorders, vol. 17, no. 6, pp. 1329-1335, 2002.
107. M. A. Melikoglu, I. Sezer, and C. Kacar, "Rheumatoid-like hand deformities in Parkinson disease," Journal of Clinical Rheumatology, vol. 13, no. 4, pp. 236-237, 2007.
108. T. Kogure, T. Tatsumi, Y. Kaneko, and K. Okamoto, "Rheumatoid arthritis accompanied by Parkinson disease," Journal of Clinical Rheumatology, vol. 14, no. 3, pp. 192-193, 2008.
109. R. C. Kunas, A. McRae, J. Kesselring, and P. M. Villiger, "Antidopaminergic antibodies in a patient with a complex autoimmune disorder and rapidly progressing Parkinsons disease," Journal of Allergy and Clinical Immunology, vol. 96, no. 5, part 1, pp. 688-690, 1995.
110. K. Yanamandra, M. A. Gruden, V. Casaite, R. Meskys, L. Forsgren, and L. A. Morozova-Roche, "α-synuclein reactive antibodies as diagnostic biomarkers in blood sera of parkinsons disease patients," PLoSONE, vol. 6, no. 4, Article IDe18513, 2011.
111. E. Masliah, E. Rockenstein, A. Adame et al., "Effects of α- synuclein immunization in a mouse model of Parkinsons disease," Neuron, vol. 46, no. 6, pp. 857-868, 2005.
112. E. Masliah, E. Rockenstein, M. Mante et al., "Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease," PLoS ONE, vol. 6, no. 4, Article ID e19338, 2011.
113. A. Schneeberger, M. Mandler, F. Mattner, and W. Schmidt, "Vaccination for Parkinsons disease," Parkinsonism and Related Disorders, vol. 18, supplement 1, pp. S11-S13, 2012.
114. J. Yong, G. Lacan, H. Dang et al., "BCG vaccine-induced neuroprotection in amousemodel of ParkinsonsDisease," PLoS ONE, vol. 6, no. 1, Article ID e16610, 2011.