Emerging roles of microglial activation and non-motor symptoms in Parkinson's disease

Progress in Neurobiology

Volumn 98, Issue 2, 2012, Pages 222-238

  Doorn, Karlijn J ^a,b   Lucassen, Paul J ^a   Boddeke, Hendrikus W ^c   Prins, Marloes ^b   Berendse, Henk W ^b   Drukarch, Benjamin ^b   van Dam, Anne Marie ^b  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^c UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

Alpha synuclein; Microglia; Neurodegeneration; Neuroinflammation; Non motor symptoms; Parkinson's disease

Indexed keywords

(3 IODOBENZYL)GUANIDINE; ALPHA SYNUCLEIN; ANTIINFLAMMATORY AGENT; B7 ANTIGEN; CD11B ANTIGEN; CD45 ANTIGEN; CD68 ANTIGEN; CD86 ANTIGEN; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR7; CHEMOKINE RECEPTOR CCR9; CHEMOKINE RECEPTOR CXCR1; CHEMOKINE RECEPTOR CXCR3; GAMMA INTERFERON; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 13; INTERLEUKIN 1BETA; INTERLEUKIN 4; INTERLEUKIN 6; LEVODOPA; NEURTURIN; TUMOR NECROSIS FACTOR ALPHA;

AUTONOMIC DYSFUNCTION; BRADYKINESIA; BRAIN DEPTH STIMULATION; CELL ACTIVATION; CELL AGING; CELL INTERACTION; CINGULATE GYRUS; COGNITION; CONSTIPATION; CYTOTOXICITY; DISEASE SEVERITY; GENE EXPRESSION; GENITAL PAIN; HIPPOCAMPUS; HUMAN; HYPOSMIA; LIMBIC SYSTEM; LOCUS CERULEUS; LOSS OF FUNCTION MUTATION; MACROPHAGE; MICROGLIA; MOUTH PAIN; MUSCLE RIGIDITY; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NOCICEPTION; OLFACTORY BULB; ORTHOSTATIC HYPOTENSION; PARASOMNIA; PARKINSON DISEASE; PATHOPHYSIOLOGY; POLARIZATION; PRIORITY JOURNAL; REVIEW; SUBSTANTIA NIGRA; TEMPORAL CORTEX; TREMOR;

ANIMALS; HUMANS; MICROGLIA; PARKINSON DISEASE;

EID: 84863487503     PISSN: 03010082     EISSN: 18735118     Source Type: Journal    
DOI: 10.1016/j.pneurobio.2012.06.005     Document Type: Review

References (242)

1. Aarsland D., Andersen K., Larsen J.P., Lolk A., Nielsen H., Kragh-Sorensen P. Risk of dementia in Parkinson's disease. Neurology 2001, 56:730-736.
2. Aarsland D., Kurz M.W. The epidemiology of dementia associated with Parkinson's disease. Brain Pathology 2010, 20:633-639.
3. Ajmone-Cat M.A., Cacci E., Minghetti L. Non steroidal anti-inflammatory drugs and neurogenesis in the adult mammalian brain. Current Pharmaceutical Design 2008, 14:1435-1442.
4. Akiyama H. Inflammatory response in Alzheimer's disease. The Tohoku Journal of Experimental Medicine 1994, 174:295-303.
5. Alafuzoff I., Ince P.G., Arzberger T., Al-Sarraj S., Bell J., Bodi I., Bogdanovic N., Bugiani O., Ferrer I., Gelpi E. Staging/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium. Acta Neuropathologica 2009, 117:635-652.
6. Allan L.E., Petit G.H., Brundin P. Cell transplantation in Parkinson's disease: problems and perspectives. Current Opinion in Neurology 2010, 23:426-432.
7. Alves G., Forsaa E.B., Pedersen K.F., Dreetz Gjerstad M., Larsen J.P. Epidemiology of Parkinson's disease. Journal of Neurology 2008, 255:18-32.
8. Amino T., Orimo S., Itoh Y., Takahashi A., Uchihara T., Mizusawa H. Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Pathology 2005, 15:29-34.
9. Antony J.M., Paquin A., Nutt S.L., Kaplan D.R., Miller F.D. Endogenous microglia regulate development of embryonic cortical precursor cells. Journal of Neuroscience Research 2011, 89:286-298.
10. Arimoto T., Bing G. Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration. Neurobiology of Disease 2003, 12:35-45.
11. Baker S.A., Baker K.A., Hagg T. Dopaminergic nigrostriatal projections regulate neural precursor proliferation in the adult mouse subventricular zone. European Journal of Neuroscience 2004, 20:575-579.
12. Baloyannis S.J., Costa V., Baloyannis I.S. Morphological alterations of the synapses in the locus coeruleus in Parkinson's disease. Journal of the Neurological Sciences 2006, 248:35-41.
13. Baron R., Nemirovsky A., Harpaz I., Cohen H., Owens T., Monsonego A. IFN-y enhances neurogenesis in wild-type mice and in a mouse model of Alzheimer's disease. The FASEB Journal 2008, 22:2843-2852.
14. Battista D., Ferrari C.C., Gage F.H., Pitossi F.J. Neurogenic niche modulation by activated microglia: transforming growth factor increases neurogenesis in the adult dentate gyrus. European Journal of Neuroscience 2006, 23:83-93.
15. Beraud D., Twomey M., Bloom B., Mittereder A., Ton V., Neitzke K., Chasovskikh S., Mhyre T.R., Maguire-Zeiss K.A. alpha-Synuclein alters toll-like receptor expression. Frontiers in Neuroscience 2011, 5:1-11.
16. Beric A., Kelly P.J., Rezai A., Sterio D., Mogilner A., Zonenshayn M., Kopell B. Complications of deep brain stimulation surgery. Stereotactic and Functional Neurosurgery 2000, 77:73-78.
17. Bernardino L., Agasse F., Silva B., Ferreira R., Grade S., Malva J.O. Tumor Necrosis Factor Modulates Survival, Proliferation, and Neuronal Differentiation in Neonatal Subventricular Zone Cell Cultures. Stem Cells 2008, 26:2361-2371.
18. Bertolotto A., Agresti C., Castello A., Manzardo E., Riccio A. 5D4 keratan sulfate epitope identifies a subset of ramified microglia in normal central nervous system parenchyma. Journal of Neuroimmunology 1998, 85:69-77.
19. Biber K., Neumann H., Inoue K., Boddeke H.W.G.M. Neuronal 'On'and 'Off' signals control microglia. Trends in Neurosciences 2007, 30:596-602.
20. Björklund A., Dunnett S.B. Dopamine neuron systems in the brain: an update. Trends in Neurosciences 2007, 30:194-202.
21. Björklund A., Schmidt R.H., Stenevi U. Functional reinnervation of the neostriatum in the adult rat by use of intraparenchymal grafting of dissociated cell suspensions from the substantia nigra. Cell and Tissue Research 1980, 212:39-45.
22. Björklund A., Stenevi U. Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Research 1979, 177:555-560.
23. Block M.L., Hong J.S. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Progress in Neurobiology 2005, 76:77-98.
24. Blum-Degena D., Müller T., Kuhn W., Gerlach M., Przuntek H., Riederer P. Interleukin-1 [beta] and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neuroscience Letters 1995, 202:17-20.
25. Boekhoorn K., Joels M., Lucassen P.J. Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus. Neurobiology of Disease 2006, 24:1-14.
26. Bohnen N.I., Albin R.L. The cholinergic system and Parkinson disease. Behavioural Brain Research 2011, 221:564-573.
27. Bosboom J.L.W., Stoffers D., Wolters E.C. Cognitive dysfunction and dementia in Parkinson's disease. Journal of Neural Transmission 2004, 111:1303-1315.
28. Braak H., Braak E. Pathoanatomy of Parkinson's disease. Journal of Neurology 2000, 247:3-10.
29. Braak H., Ghebremedhin E., Rüb U., Bratzke H., Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell and Tissue Research 2004, 318:121-134.
30. Braak H., Tredici K.D., Rüb U., de Vos R.A.I., Jansen Steur E.N.H., Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiology of Aging 2003, 24:197-211.
31. Brundin P., Li J.Y., Holton J.L., Lindvall O., Revesz T. Research in motion: the enigma of Parkinson's disease pathology spread. Nature Reviews Neuroscience 2008, 9:741-745.
32. Butovsky O., Talpalar A.E., Ben-Yaakov K., Schwartz M. Activation of microglia by aggregated [beta]-amyloid or lipopolysaccharide impairs MHC-II expression and renders them cytotoxic whereas IFN-[gamma] and IL-4 render them protective. Molecular and Cellular Neuroscience 2005, 29:381-393.
33. Cacci E., Ajmone Cat M.A., Anelli T., Biagioni S., Minghetti L. In vitro neuronal and glial differentiation from embryonic or adult neural precursor cells are differently affected by chronic or acute activation of microglia. Glia 2008, 56:412-425.
34. Carpentier P.A., Palmer T.D. Immune influence on adult neural stem cell regulation and function. Neuron. 2009, 64:79-92.
35. Cersosimo M.G., Benarroch E.E. Pathological correlates of gastrointestinal dysfunction in Parkinson's disease. Neurobiology of Disease 2011, 10.1016/j.nbd.2011.10.014.
36. Chaudhuri K., Healy D.G., Schapira A.H.V. Non-motor symptoms of Parkinson's disease: diagnosis and management. The Lancet Neurology 2006, 5:235-245.
37. Chen H., Jacobs E., Schwarzschild M.A., McCullough M.L., Calle E.E., Thun M.J., Ascherio A. Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Annals of Neurology 2005, 58:963-967.
38. Choi D.Y., Zhang J., Bing G. Aging enhances the neuroinflammatory response and [alpha]-synuclein nitration in rats. Neurobiology of Aging 2010, 31:1649-1653.
39. Clausen B.H., Lambertsen K.L., Babcock A.A., Holm T.H., gnaes-Hansen F., Finsen B. Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice. Journal of Neuroinflammation 2008, 5:46-56.
40. Colton C., Mott R., Sharpe H., Xu Q., Van Nostrand W., Vitek M. Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. Journal of Neuroinflammation 2006, 3:27.
41. Colton C.A. Heterogeneity of microglial activation in the innate immune response in the brain. Journal of Neuroimmune Pharmacology 2009, 4:399-418.
42. Colton C.A., Wilcock D.M. Assessing activation states in microglia. CNS &# 38. Neurological Disorders-Drug Targets (Formerly Current Drug Targets) 2010, 9:174-191.
43. Conway K.A., Harper J.D., Lansbury P.T. Accelerated in vitro fibril formation by a mutant -synuclein linked to early-onset Parkinson disease. Nature Medicine 1998, 4:1318-1320.
44. Croisier E., Moran L.B., Dexter D.T., Pearce R.K.B., Graeber M.B. Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition. Journal of Neuroinflammation 2005, 2:14-22.
45. Cunningham C., Wilcockson D.C., Campion S., Lunnon K., Perry V.H. Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. The Journal of Neuroscience 2005, 25:9275-9284.
46. Czeh M., Gressens P., Kaindl A.M. The Yin and Yang of Microglia. Developmental Neuroscience 2011, 33:199-209.
47. Danzer K.M., Haasen D., Karow A.R., Moussaud S., Habeck M., Giese A., Kretzschmar H., Hengerer B., Kostka M. Different species of alpha-synuclein oligomers induce calcium influx and seeding. The Journal of Neuroscience 2007, 27:9220-9232.
48. Danzer K.M., McLean P.J. Drug Targets from Genetics: Alpha-Synuclein. CNS & Neurological Disorders Drug Targets 2011, 10:712-723.
49. Dauer W., Przedborski S. Parkinson's Disease: Mechanisms and Models. Neuron 2003, 39:889-909.
50. David S., Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nature Reviews Neuroscience 2011, 12:388-399.
51. De Haas A.H., Boddeke H.W.G.M., Biber K. Region specific expression of immunoregulatory proteins on microglia in the healthy CNS. Glia 2008, 56:888-894.
52. de Lau L.M.L., Schipper C.M.A., Hofman A., Koudstaal P.J., Breteler M. Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam Study. Archives of Neurology 2005, 62:1265-1269.
53. DeBoy C.A., Xin J., Byram S.C., Serpe C.J., Sanders V.M., Jones K.J. Immune-mediated neuroprotection of axotomized mouse facial motoneurons is dependent on the IL-4/STAT6 signaling pathway in CD4+ T cells. Experimental Neurology 2006, 201:212-224.
54. Dickson D.W., Fujishiro H., Orr C., DelleDonne A., Josephs K.A., Frigerio R., Burnett M., Parisi J.E., Klos K.J., Ahlskog J.E. Neuropathology of non-motor features of Parkinson disease. Parkinsonism & Related Disorders 2009, 15:S1-S5.
55. Dilger R.N., Johnson R.W. Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system. Journal of Leukocyte Biology 2008, 84:932-939.
56. Dodel R.C., Lohmüller F., Du Y., Eastwood B., Gocke P., Oertel W.H., Gasser T. A polymorphism in the intronic region of the IL-1alpha gene and the risk for Parkinson's disease. Neurology 2001, 56:982-983.
57. Doty R.L. Olfaction in Parkinson's disease and related disorders. Neurobiology of Disease 2011, 10.1016/j.nbd.2011.10.026.
58. Doty R.L., Hawkes C.H., Berendse H.W. Olfactory dysfunction in Parkinson's disease and related disorders. Non-dopamine Lesions in Parkinson's Disease 2011, 65-91. G.M. Halliday, R.A. Barker, D.B. Rowe (Eds.).
59. Duarte E.P., Saavedra A., Baltazar G. GDNF: a key player in neuron-glia crosstalk and survival of nigrostriatal dopaminergic neurons. Interaction Between Neurons and Glia in Aging and Disease 2007, 173-192.
60. Ekdahl C.T., Claasen J.H., Bonde S., Kokaia Z., Lindvall O. Inflammation is detrimental for neurogenesis in adult brain. Proceedings of the National Academy of Sciences of the United States of America 2003, 100:13632-21363.
61. Evans J., Revesz T., Barker R.A. Lesions associated with cognitive impairment and dementia. Non-dopamine Lesions in Parkinson's Disease 2011, 261-287. G.M. Halliday, R.A. Barker, D.B. Rowe (Eds.).
62. Fahn S., Halliday A. Lesions associated with the classic triad of Parkinsonian motor features. Non-dopamine Lesions in Parkinson's Disease 2011, 3-17. G.M. Halliday, R.A. Barker, D.B. Rowe (Eds.).
63. Farfara D., Lifshitz V., Frenkel D. Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease. Journal of Cellular and Molecular Medicine 2008, 12:762-780.
64. Fenn A.M., Henry C.J., Huang Y., Dugan A., Godbout J.P. Lipopolysaccharide-induced interleukin (IL)-4 receptor-alpha expression and corresponding sensitivity to the M2 promoting effects of IL-4 are impaired in microglia of aged mice. Brain, Behavior, and Immunity 2011, 10.1016/j.bbi.2011.10.003.
65. Fleming S.M., Tetreault N.A., Mulligan C.K., Hutson C.B., Masliah E., Chesselet M.F. Olfactory deficits in mice overexpressing human wildtype alpha-synuclein. European Journal of Neuroscience 2008, 28:247-256.
66. Gaenslen A., Swid I., Liepelt Scarfone I., Godau J., Berg D. The patients' perception of prodromal symptoms before the initial diagnosis of Parkinson's disease. Movement Disorders 2011, 26:653-658.
67. Gagnon J.F., Postuma R.B., Mazza S., Doyon J., Montplaisir J. Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. The Lancet Neurology 2006, 5:424-432.
68. Gao H.M., Hong J.S. Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends in Immunology 2008, 29:357-365.
69. Gao H.M., Hong J.S., Zhang W., Liu B. Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson's disease. The Journal of Neuroscience 2003, 23:1228-1236.
70. Gao X., Chen H., Schwarzschild M.A., Ascherio A. Use of ibuprofen and risk of Parkinson disease. Neurology 2011, 76:863-869.
71. Gasser T. Molecular pathogenesis of Parkinson disease: insights from genetic studies. Expert Reviews in Molecular Medicine 2009, 11:1-20.
72. Gensel J.C., Nakamura S., Guan Z., van Rooijen N., Ankeny D.P., Popovich P.G. Macrophages promote axon regeneration with concurrent neurotoxicity. The Journal of Neuroscience 2009, 29:3956-3968.
73. Gerhard A., Pavese N., Hotton G., Turkheimer F., Es M., Hammers A., Eggert K., Oertel W., Banati R.B., Brooks D.J. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiology of Disease 2006, 21:404-412.
74. Giasson B.I., Duda J.E., Murray I.V.J., Chen Q., Souza J.M., Hurtig H.I., Ischiropoulos H., Trojanowski J.Q. Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 2000, 290:985-989.
75. Gill S.S., Patel N.K., Hotton G.R., O'Sullivan K., McCarter R., Bunnage M., Brooks D.J., Svendsen C.N., Heywood P. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nature Medicine 2003, 9:589-595.
76. Gjerstad M.D., Boeve B., Wentzel-Larsen T., Aarsland D., Larsen J.P. Occurrence and clinical correlates of REM sleep behaviour disorder in patients with Parkinson's disease over time. Journal of Neurology, Neurosurgery & Psychiatry 2008, 79:387-391.
77. Glass C.K., Saijo K., Winner B., Marchetto M.C., Gage F.H. Mechanisms underlying inflammation in neurodegeneration. Cell 2010, 140:918-934.
78. Glezer I., Simard A.R., Rivest S. Neuroprotective role of the innate immune system by microglia. Neuroscience 2007, 147:867-883.
79. Global Parkinson's Disease Survey Steering Committee Factors impacting on quality of life in Parkinson's disease: results from an international survey. Movement Disorders 2002, 17:60-67.
80. Goldberg M.S., Lansbury P.T. Is there a cause-and-effect relationship between -synuclein fibrillization and Parkinson's disease?. Nature Cell Biology 2000, 2:E115-E119.
81. Goldstein D.S., Holmes C.S., Dendi R., Bruce S.R., Li S.T. Orthostatic hypotension from sympathetic denervation in Parkinson's disease. Neurology 2002, 58:1247-1255.
82. Gordon S., Martinez F.O. Alternative activation of macrophages: mechanism and functions. Immunity 2010, 32:593-604.
83. Graeber M.B., Streit W.J. Microglia: biology and pathology. Acta Neuropathologica 2010, 119:89-105.
84. Grinberg L.T., Rueb U., Alho A.T.L., Heinsen H. Brainstem pathology and non-motor symptoms in PD. Journal of the Neurological Sciences 2010, 289:81-88.
85. Ha A.D., Jankovic J. Pain in Parkinson's disease. Movement Disorders 2011, 10.1002/mds.23959.
86. Haehner A., Boesveldt S., Berendse H.W., kay-Sim A., Fleischmann J., Silburn P.A., Johnston A.N., Mellick G.D., Herting B., Reichmann H. Prevalence of smell loss in Parkinson's disease-A multicenter study. Parkinsonism & Related Disorders 2009, 15:490-494.
87. Haehner A., Hummel T., Reichmann H. Olfactory loss in Parkinson's disease. Parkinson's Disease 2011, 10.4061/2011/450939.
88. Halliday A., Barker R.A., Rowe D.B. Non-dopamine Lesions in Parkinson's Disease 2011, Oxford University Press, Inc, New York.
89. Hanisch U.K., Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nature Neuroscience 2007, 10:1387-1394.
90. Hansen C., Angot E., Bergstr÷m A.L., Steiner J.A., Pieri L., Paul G., Outeiro T.F., Melki R., Kallunki P., Fog K. Alpha-synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. The Journal of Clinical Investigation 2011, 121:715-725.
91. Hawkes C.H., Shephard B.C., Daniel S.E. Olfactory dysfunction in Parkinson's disease. Journal of Neurology, Neurosurgery & Psychiatry 1997, 62:436-446.
92. Hawkes C.H., Shephard B.C., Daniel S.E. Is Parkinson's disease a primary olfactory disorder?. QJM 1999, 92:473-480.
93. Hely M.A., Morris J.G.L., Reid W.G.J., Trafficante R. Sydney multicenter study of Parkinson's disease: Non L dopa-responsive problems dominate at 15 years. Movement Disorders 2005, 20:190-199.
94. Henkel J.S., Engelhardt J.I., Sikl≤s L., Simpson E.P., Kim S.H., Pan T., Goodman J.C., Siddique T., Beers D.R., Appel S.H. Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Annals of Neurology 2004, 55:221-235.
95. Henry C.J., Huang Y., Wynne A.M., Godbout J.P. Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1 [beta] and anti-inflammatory IL-10 cytokines. Brain, Behavior, and Immunity 2009, 23:309-317.
96. Hirsch E.C., Hunot S. Neuroinflammation in Parkinson's disease: a target for neuroprotection?. The Lancet Neurology 2009, 8:382-397.
97. Hirsch E.C., Vyas S., Hunot S. Neuroinflammation in Parkinson's disease. Parkinsonism & Related Disorders 2012, 18:S210-S212.
98. Hoglinger G.U., Rizk P., Muriel M.P., Duyckaerts C., Oertel W.H., Caille I., Hirsch E.C. Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nature Neuroscience 2004, 7:726-735.
99. Imamura K., Hishikawa N., Ono K., Suzuki H., Sawada M., Nagatsu T., Yoshida M., Hashizume Y. Cytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains. Acta Neuropathologica 2005, 109:141-150.
100. Imamura K., Hishikawa N., Sawada M., Nagatsu T., Yoshida M., Hashizume Y. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson's disease brains. Acta Neuropathologica 2003, 106:518-526.
101. Isacson O., Bjorklund L.M., Schumacher J.M. Toward full restoration of synaptic and terminal function of the dopaminergic system in Parkinson's disease by stem cells. Annals of Neurology 2003, 53:S135-S148.
102. Jankovic J. Parkinson's disease: clinical features and diagnosis, Journal of Neurology. Neurosurgery & Psychiatry 2008, 79:368.
103. Jayadev S., Nesser N.K., Hopkins S., Myers S.J., Case A., Lee R.J., Seaburg L.A., Uo T., Murphy S.P., Morrison R.S. Transcription factor p53 influences microglial activation phenotype. Glia 2011, 59:1402-1413.
104. Jellinger K.A. Synuclein deposition and non-motor symptoms in Parkinson disease. Journal of the neurological sciences 2011, 310:107-111.
105. Johnson S.M.Y.R. An age-related decline in interleukin-10 may contribute to the increased expression of interleukin-6 in brain of aged mice. Neuroimmunomodulation 2001, 9:183-192.
106. Jurgens H.A., Johnson R.W. Dysregulated neuronal-microglial cross-talk during aging, stress and inflammation. Experimental Neurology 2010, 10.1016/j.expneurol.2010.11.014.
107. Kigerl K.A., Gensel J.C., Ankeny D.P., Alexander J.K., Donnelly D.J., Popovich P.G. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. The Journal of Neuroscience 2009, 29:13435-13444.
108. Kim J.H., Lee H.W., Hwang J., Kim J., Lee M.J., Han H.S., Lee W.H., Suk K. Microglia-inhibiting activity of Parkinson's disease drug amantadine. Neurobiology of Aging 2011, 10.1016/j.neurobiolaging.2011.08.011.
109. Klegeris A., McGeer P.L. Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory agents in the treatment of neurodegenerative disease. Current Alzheimer Research 2005, 2:355-365.
110. Koprich J.B., Reske-Nielsen C., Mithal P., Isacson O. Neuroinflammation mediated by IL-1 increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease. Journal of Neuroinflammation 2008, 5:8-20.
111. Kordower J.H., Herzog C.D., Dass B., Bakay R.A.E., Stansell J., Gasmi M., Bartus R.T. Delivery of neurturin by AAV2 (CERE 120) mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP treated monkeys. Annals of Neurology 2006, 60:706-715.
112. Kreutzberg G.W. Microglia: a sensor for pathological events in the CNS. Trends in Neurosciences 1996, 19:312-318.
113. Kuzumaki N., Ikegami D., Imai S., Narita M., Tamura R., Yajima M., Suzuki A., Miyashita K., Niikura K., Takeshima H. Enhanced IL 1 production in response to the activation of hippocampal glial cells impairs neurogenesis in aged mice. Synapse 2010, 64:721-728.
114. Ledeboer A., Breve J.J.P., Poole S., Tilders F.J.H., Van Dam A.M. Interleukin 10, interleukin 4, and transforming growth factor differentially regulate lipopolysaccharide induced production of pro inflammatory cytokines and nitric oxide in co cultures of rat astroglial and microglial cells. Glia 2000, 30:134-142.
115. Lee S.J., Desplats P., Sigurdson C., Tsigelny I., Masliah E. Cell-to-cell transmission of non-prion protein aggregates. Nature Reviews Neurology 2010, 6:702-706.
116. Li J.Y., Englund E., Holton J.L., Soulet D., Hagell P., Lees A.J., Lashley T., Quinn N.P., Rehncrona S., Bjorklund A. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nature Medicine 2008, 14:501-503.
117. Lim Y., Kehm V.M., Lee E.B., Soper J.H., Li C., Trojanowski J.Q., Lee V.M.Y. Alpha-syn Suppression Reverses Synaptic and Memory Defects in a Mouse Model of Dementia with Lewy Bodies. The Journal of Neuroscience 2011, 31:10076-10087.
118. Lindvall O., Kokaia Z. Stem cells in human neurodegenerative disorders; time for clinical translation?. The Journal of Clinical Investigation 2010, 120:29-40.
119. Lindvall O., Widner H., Rehncrona S., Brundin P., Odin P., Gustavii B., Frackowiak R., Leenders K.L., Sawle G., Rothwell J.C. Transplantation of fetal dopamine neurons in Parkinson's disease: One year clinical and neurophysiological observations in two patients with putaminal implants. Annals of Neurology 1992, 31:155-165.
120. Lloyd K.G., Davidson L., Hornykiewicz O. The neurochemistry of Parkinson's disease: effect of L-dopa therapy. Journal of Pharmacology and Experimental Therapeutics 1975, 195:453-464.
121. Long-Smith C.M., Sullivan A.M., Nolan Y.M. The influence of microglia on the pathogenesis of Parkinson's disease. Progress in Neurobiology 2009, 89:277-287.
122. Lucassen P.J., Meerlo P., Naylor A.S., Van Dam A.M., Dayer A.G., Fuchs E., Oomen C.A., Czéh B. Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action. European Neuropsychopharmacology 2010, 20:1-17.
123. Lucin K.M., Wyss-Coray T. Immune activation in brain aging and neurodegeneration: too much or too little?. Neuron 2009, 64:110-122.
124. Lull M.E., Block M.L. Microglial activation and chronic neurodegeneration. Neurotherapeutics 2010, 7:354-365.
125. Lyons A., Downer E.J., Crotty S., Nolan Y.M., Mills K.H.G., Lynch M.A. CD200 Ligand-receptor interaction modulates microglial activation in vivo and in vitro: a role for IL-4. The Journal of Neuroscience 2007, 27:8309-8313.
126. Mantovani A., Sica A., Sozzani S., Allavena P., Vecchi A., Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends in Immunology 2004, 25:677-686.
127. Mantovani A., Sozzani S., Locati M., Allavena P., Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends in Immunology 2002, 23:549-555.
128. Marlatt M.W., Lucassen P.J. Neurogenesis and alzheimers disease: biology and pathophysiology in mice and men. Current Alzheimer Research 2010, 7:113-125.
129. Mayberg H.S., Solomon D.H. Depression in Parkinson's disease: a biochemical and organic viewpoint. Advances in Neurology 1995, 65:49-60.
130. McGeer E.G., Klegeris A., McGeer P.L. Inflammation, the complement system and the diseases of aging. Neurobiology of Aging 2005, 26:94-97.
131. McGeer P.L., Itagaki S., Boyes B.E., McGeer E.G. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 1988, 38:1285.
132. McGeer P.L., McGeer E.G. Inflammation and the degenerative diseases of aging. Annals of New York Academy of Science 2004, 1035:104-116.
133. McGeer P.L., McGeer E.G. Glial reactions in Parkinson's disease. Movement Disorders 2008, 23:474-483.
134. McGeer P.L., Yasojima K., McGeer E.G. Association of interleukin-1 [beta] polymorphisms with idiopathic Parkinson's disease. Neuroscience Letters 2002, 326:67-69.
135. Mendez I., Viñuela A., Astradsson A., Mukhida K., Hallett P., Robertson H., Tierney T., Holness R., Dagher A., Trojanowski J.Q. Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years. Nature Medicine 2008, 14:507-509.
136. Mogi M., Harada M., Kondo T., Riederer P., Inagaki H., Minami M., Nagatsu T. Interleukin-1 [beta], interleukin-6, epidermal growth factor and transforming growth factor-[alpha] are elevated in the brain from parkinsonian patients. Neuroscience Letters 1994, 180:147-150.
137. Mogi M., Harada M., Riederer P., Narabayashi H., Fujita K., Nagatsu T. Tumor necrosis factor-[alpha](TNF-[alpha]) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neuroscience Letters 1994, 165:208-210.
138. Monje M.L., Toda H., Palmer T.D. Inflammatory blockade restores adult hippocampal neurogenesis. Science 2003, 302:1760-1765.
139. Moore A.H., Bigbee M.J., Boynton G.E., Wakeham C.M., Rosenheim H.M., Staral C.J., Morrissey J.L., Hund A.K. Non-Steroidal anti-inflammatory drugs in Alzheimer's Disease and Parkinson's Disease. Reconsidering the role of neuroinflammation. Pharmaceuticals 2010, 3:1812-1841.
140. Mosser D.M., Edwards J.P. Exploring the full spectrum of macrophage activation. Nature Reviews Immunology 2008, 8:958-969.
141. Nagatsu T., Mogi M., Ichinose H., Togarr A. Changes in cytokines and neurotrophins in Parkinson's disease. Advances in Research on Neurodegeneration 2000, 8:277-290.
142. Nagatsu T., Sawada M. Cellular and molecular mechanisms of Parkinson's disease: neurotoxins, causative genes, and inflammatory cytokines. Cellular and Molecular Neurobiology 2006, 26:779-800.
143. Neeper S.A., Gomez-Pinilla F., Choi J., Cotman C. Exercise and brain neurotrophins. Nature 1995, 373:109.
144. Neumann H. Control of glial immune function by neurons. Glia 2001, 36:191-199.
145. Nimmerjahn A., Kirchhoff F., Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005, 308:1314-1318.
146. Nishimura M., Mizuta I., Mizuta E., Yamasaki S., Ohta M., Kuno S. Influence of interleukin-1 [beta] gene polymorphisms on age-at-onset of sporadic Parkinson's disease. Neuroscience Letters 2000, 284:73-76.
147. Nolan Y., Maher F.O., Martin D.S., Clarke R.M., Brady M.T., Bolton A.E., Mills K.H.G., Lynch M.A. Role of interleukin-4 in regulation of age-related inflammatory changes in the hippocampus. Journal of Biological Chemistry 2005, 280:9354-9362.
148. Nuber S., Petrasch-Parwez E., Arias-Carrió|n O., Koch L., Kohl Z., Schneider J., Calaminus C., Dermietzel R., Samarina A., Boy J. Olfactory neuron-specific expression of A30P alpha-synuclein exacerbates dopamine deficiency and hyperactivity in a novel conditional model of early Parkinson's disease stages. Neurobiology of Disease 2011, 44:192-204.
149. Oka H., Toyoda C., Yogo M., Mochio S. Olfactory dysfunction and cardiovascular dysautonomia in Parkinson's disease. Journal of Neurology 2010, 257:969-976.
150. Olah M., Biber K., Vinet J., WGM Boddeke H. Microglia phenotype diversity. CNS Neurological Disorders-Drug Targets (formerly Current Drug Targets) 2011, 10:108-118.
151. Olah M., Ping G., De Haas A.H., Brouwer N., Meerlo P., Van Der Zee E.A., Biber K., Boddeke H.W.G.M. Enhanced hippocampal neurogenesis in the absence of microglia T cell interaction and microglia activation in the murine running wheel model. Glia 2009, 57:1046-1061.
152. Olson E.J., Boeve B.F., Silber M.H. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain 2000, 123:331-339.
153. Orimo S., Takahashi A., Uchihara T., Mori F., Kakita A., Wakabayashi K., Takahashi H. Degeneration of cardiac sympathetic nerve begins in the early disease process of Parkinson's disease. Brain Pathology 2007, 17:24-30.
154. Orr C.F., Rowe D.B., Halliday G.M. An inflammatory review of Parkinson's disease. Progress in Neurobiology 2002, 68:325-340.
155. Ouchi Y., Yagi S., Yokokura M., Sakamoto M. Neuroinflammation in the living brain of Parkinson's disease. Parkinsonism & Related Disorders 2009, 15:S200-S204.
156. Ouchi Y., Yoshikawa E., Sekine Y., Futatsubashi M., Kanno T., Ogusu T., Torizuka T. Microglial activation and dopamine terminal loss in early Parkinson's disease. Annals of Neurology 2005, 57:168-175.
157. Parkinson J. An essay on the shaking palsy. Journal of Neuropsychiatry and Clinical Neurosciences 2002, 14:223-236.
158. Parkkinen L., Pirttila T., Tervahauta M., Alafuzoff I. Widespread and abundant synuclein pathology in a neurologically unimpaired subject. Neuropathology 2005, 25:304-314.
159. Pasqualetti P., Bonomini C., Dal Forno G., Paulon L., Sinforiani E., Marra C., Zanetti O., Rossini P.M. A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer's disease. Aging Clinical and Experimental Research 2009, 21:102-110.
160. Perry V.H. Contribution of systemic inflammation to chronic neurodegeneration. Acta Neuropathologica 2010, 120:277-286.
161. Perry V.H., Cunningham C., Holmes C. Systemic infections and inflammation affect chronic neurodegeneration. Nature Reviews Immunology 2007, 7:161-167.
162. Perry V.H., Hume D.A., Gordon S. Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 1985, 15:313-326.
163. Perry V.H., Matyszak M.K., Fearn S. Altered antigen expression of microglia in the aged rodent CNS. Glia 1993, 7:60-67.
164. Perry V.H., Nicoll J.A.R., Holmes C. Microglia in neurodegenerative disease. Nature Reviews Neurology 2010, 6:193-201.
165. Pfeiffer R.F. Neuroinflammation and Parkinson disease. Neurology 2009, 73:1462-1468.
166. Pocock J.M., Kettenmann H. Neurotransmitter receptors on microglia. Trends in Neurosciences 2007, 30:527-535.
167. Poewe W. Treatments for Parkinson disease-past achievements and current clinical needs. Neurology 2009, 72:S65-S73.
168. Polazzi E., Monti B. Microglia and neuroprotection: from in vitro studies to therapeutic applications. Progress in Neurobiology 2010, 92:293-315.
169. Ponsen M.M., Stoffers D., Booij J., van Eck Smit B.L.F., Wolters E.C., Berendse H.W. Idiopathic hyposmia as a preclinical sign of Parkinson's disease. Annals of Neurology 2004, 56:173-181.
170. Ponsen M.M., Stoffers D., Wolters E.C., Booij J., Berendse H.W. Olfactory testing combined with dopamine transporter imaging as a method to detect prodromal Parkinson's disease. Journal of Neurology, Neurosurgery & Psychiatry 2010, 81:396-399.
171. Postuma R.B., Gagnon J.F., Vendette M., Fantini M.L., Massicotte-Marquez J., Montplaisir J. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology 2009, 72:1296.
172. Potter P.E. Investigational medications for treatment of patients with Alzheimer disease. JAOA: Journal of the American Osteopathic Association 2010, 110:S27.
173. Qian L., Flood P.M., Hong J.S. Neuroinflammation is a key player in Parkinson's disease and a prime target for therapy. Journal of Neural Transmission 2010, 117:971-979.
174. Qin L., Wu X., Block M.L., Liu Y., Breese G.R., Hong J.S., Knapp D.J., Crews F.T. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 2007, 55:453-462.
175. Ransohoff R.M., Perry V.H. Microglial physiology: unique stimuli, specialized responses. Annual Review of Immunology 2009, 27:119-145.
176. Reichmann H., Schneider C., Löhle M. Non-motor features of Parkinson's disease: depression and dementia. Parkinsonism & Related Disorders 2009, 15:S87-S92.
177. Remy P., Doder M., Lees A., Turjanski N., Brooks D. Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 2005, 128:1314-1322.
178. Reynolds A.D., Glanzer J.G., Kadiu I., Ricardo Dukelow M., Chaudhuri A., Ciborowski P., Cerny R., Gelman B., Thomas M.P., Mosley R.L. Nitrated alpha synuclein activated microglial profiling for Parkinson's disease. Journal of Neurochemistry 2008, 104:1504-1525.
179. Roodveldt C., Christodoulou J., Dobson C.M. Immunological features of synuclein in Parkinson's disease. Journal of Cellular and Molecular Medicine 2008, 12:1820-1829.
180. Rugbjerg K., Friis S., Ritz B., Schernhammer E.S., Korbo L., Olsen J.H. Autoimmune disease and risk for Parkinson disease. Neurology 2009, 73:1462-1468.
181. Russo-Neustadt A.A., Beard R.C., Huang Y.M., Cotman C.W. Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus. Neuroscience 2000, 101:305-312.
182. Saijo K., Winner B., Carson C.T., Collier J.G., Boyer L., Rosenfeld M.G., Gage F.H., Glass C.K. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 2009, 137:47-59.
183. Samii A., Nutt J.G., Ransom B.R. Parkinson's disease. Lancet 2004, 363:1783-1793.
184. Sanchez-Guajardo V., Febbraro F., Kirik D., Romero-Ramos M. Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease. PloS One 2010, 5:e8784.
185. Schapira A.H.V., Olanow C.W. Neuroprotection in Parkinson disease. JAMA: The Journal of the American Medical Association 2004, 291:358-364.
186. Schulte T., Schols L., Muller T., Woitalla D., Berger K., Kruger R. Polymorphisms in the interleukin-1 alpha and beta genes and the risk for Parkinson's disease. Neuroscience Letters 2002, 326:70-72.
187. Schulz J.B., Gerlach M., Gille G., Kuhn W., Müngersdorf M., Riederer P., S3dmeyer M., Ludolph A. Basic science in Parkinson's disease: its impact on clinical practice. Journal of Neurology 2011, 258:299-306.
188. Schwartz M. Macrophages and Microglia in Central Nervous System Injury: Are They Helpful or Harmful?. Journal of Cerebral Blood Flow & Metabolism 2003, 23:385-394.
189. Schwartz M. Tissue-repairing blood-derived macrophages are essential for healing of the injured spinal cord: From skin-activated macrophages to infiltrating blood-derived cells?. Brain Behavior and Immunity 2010, 24:1054-1057.
190. Schwartz M., Butovsky O., Bruck W., Hanisch U.K. Microglial phenotype: is the commitment reversible?. Trends in Neurosciences 2006, 29:68-74.
191. Schwartz M., London A., Shechter R. Boosting T-cell immunity as a therapeutic approach for neurodegenerative conditions: the role of innate immunity. Neuroscience 2009, 158:1133-1142.
192. Schwartz M., Shechter R. Systemic inflammatory cells fight off neurodegenerative disease. Nature Reviews Neurology 2010, 6:405-410.
193. Shahed J., Jankovic J. Exploring the relationship between essential tremor and Parkinson's disease. Parkinsonism & Related Disorders 2007, 13:67-76.
194. Shulman L.M., Taback R.L., Bean J., Weiner W.J. Comorbidity of the nonmotor symptoms of Parkinson's disease. Movement Disorders 2001, 16:507-510.
195. Shulman L.M., Taback R.L., Rabinstein A.A., Weiner W.J. Non-recognition of depression and other non-motor symptoms in Parkinson's disease. Parkinsonism & Related Disorders 2002, 8:193-197.
196. Sierra A., Encinas J.M., Deudero J.J.P., Chancey J.H., Enikolopov G., Overstreet-Wadiche L.S., Tsirka S.E., Maletic-Savatic M. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 2010, 7:483-495.
197. Sierra A., Gottfried Blackmore A.C., McEwen B.S., Bulloch K. Microglia derived from aging mice exhibit an altered inflammatory profile. Glia 2007, 55:412-424.
198. Sierra A., Gottfried-Blackmore A.C., McEwen B.S., Bulloch K. Microglia derived from aging mice exhibit an altered inflammatory profile. Glia 2007, 55:412-424.
199. Simard A.R., Rivest S. Role of inflammation in the neurobiology of stem cells. Neuroreport 2004, 15:2305-2310.
200. Simard A.R., Rivest S. Neuroprotective effects of resident microglia following acute brain injury. The Journal of Comparative Neurology 2007, 504:716-729.
201. Soldner F., Hockemeyer D., Beard C., Gao Q., Bell G.W., Cook E.G., Hargus G., Blak A., Cooper O., Mitalipova M. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 2009, 136:964-977.
202. Spiegel J., Müllers M.O., Jost W.H., Fuss G., Samnick S., Dillmann U., Becker G., Kirsch C.M. FP CIT and MIBG scintigraphy in early Parkinson's disease. Movement Disorders 2005, 20:552-561.
203. Spillantini M.G., Crowther R.A., Jakes R., Hasegawa M., Goedert M. Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proceedings of the National Academy of Sciences 1998, 95:6469-6647.
204. Sriram K., Matheson J.M., Benkovic S.A., Miller D.B., Luster M.I., O'Callaghan J.P. Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity: implications for Parkinson's disease. The FASEB Journal 2002, 16:1474-1476.
205. Sriram K., Matheson J.M., Benkovic S.A., Miller D.B., Luster M.I., O'Callaghan J.P. Deficiency of TNF receptors suppresses microglial activation and alters the susceptibility of brain regions to MPTP-induced neurotoxicity: role of TNF-alpha. The FASEB Journal 2006, 20:670-682.
206. Streit W.J. Microglial senescence: does the brain's immune system have an expiration date?. Trends in Neurosciences 2006, 29:506-510.
207. Streit W.J., Braak H., Xue Q.S., Bechmann I. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease. Acta Neuropathologica 2009, 118:475-485.
208. Streit W.J., Xue Q.S. The Brain's aging immune system. Aging and Disease 2010, 1:254-261.
209. Tanaka J., Maeda N. Microglial ramification requires nondiffusible factors derived from astrocytes. Experimental Neurology 1996, 137:367-375.
210. Tansey M.G., Goldberg M.S. Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention. Neurobiology of Disease 2010, 37:510-518.
211. Tarkowski E., Andreasen N., Tarkowski A., Blennow K. Intrathecal inflammation precedes development of Alzheimer's disease. Journal of Neurology. Neurosurgery & Psychiatry 2003, 74:1200-1205.
212. Tissingh G., Berendse H.W., Bergmans P., DeWaard R., Drukarch B., Stoof J.C., Wolters E.C. Loss of olfaction in de novo and treated Parkinson's disease: possible implications for early diagnosis. Movement Disorders 2001, 16:41-46.
213. Tompkins M.M., Hill W.D. Contribution of somal Lewy bodies to neuronal death. Brain Research 1997, 775:24-29.
214. Torres E.M., Monville C., Gates M.A., Bagga V., Dunnett S.B. Improved survival of young donor age dopamine grafts in a rat model of Parkinson's disease. Neuroscience 2007, 146:1606-1617.
215. Toulouse A., Sullivan A.M. Progress in Parkinson's disease-Where do we stand?. Progress in Neurobiology 2008, 85:376-392.
216. Tsigelny I.F., Sharikov Y., Miller M.A., Masliah E. Mechanism of alpha-synuclein oligomerization and membrane interaction: theoretical approach to unstructured proteins studies. Nanomedicine: Nanotechnology, Biology and Medicine 2008, 4:350-357.
217. Tsui A., Isacson O. Functions of the nigrostriatal dopaminergic synapse and the use of neurotransplantation in Parkinson's disease. Journal of Neurology 2011, 258:1393-1405.
218. Tysnes O.B., Müller B., Larsen J.P. Are dysautonomic and sensory symptoms present in early Parkinson's disease?. Acta Neurologica Scandinavica 2010, 122:72-77.
219. van den Berge S.A., van Strien M.E., Korecka J.A., Dijkstra A.A., Sluijs J.A., Kooijman L., Eggers R., De Filippis L., Vescovi A.L., Verhaagen J. The proliferative capacity of the subventricular zone is maintained in the parkinsonian brain. Brain 2011, 134:3249-3263.
220. van Strien M.E., Mercier D., Drukarch B., Brevθ J.J.P., Poole S., Binnekade R., Bol J., Blits B., Verhaagen J., Van Dam A.M. Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages. Gene Therapy 2010, 17:662-671.
221. Veazey C., Ozlem Erden Aki S., Cook K.F., Lai E.C., Kunik M.E. Prevalence and treatment of depression in Parkinson's disease. Journal of Neuropsychiatry and Clinical Neurosciences 2005, 17:310-323.
222. von Bohlen, Halbach O. Immunohistological markers for staging neurogenesis in adult hippocampus. Cell and Tissue Research 2007, 329:409-420.
223. Vroon A., Drukarch B., Bol J.G.J.M., Cras P., Brevé J.J.P., Allan S.M., Relton J.K., Hoogland P.V.J.M., Van Dam A.M. Neuroinflammation in Parkinson's patients and MPTP-treated mice is not restricted to the nigrostriatal system: Microgliosis and differential expression of interleukin-1 receptors in the olfactory bulb. Experimental Gerontology 2007, 42:762-771.
224. Walter L., Neumann H. Role of microglia in neuronal degeneration and regeneration. Seminars in Immunopathology 2009, 31:513-525.
225. Wee Y.V. Inflammation in neurological disorders: a help or a hindrance?. The Neuroscientist: A Review Journal Bringing Neurobiology, Neurology and Psychiatry 2010, 16:408-420.
226. Welser J.V., Li L., Milner R. Microglial activation state exerts a biphasic influence on brain endothelial cell proliferation by regulating the balance of TNF and TGF- 1. Journal of Neuroinflammation 2010, 7:89-96.
227. Winner B., Jappelli R., Maji S.K., Desplats P.A., Boyer L., Aigner S., Hetzer C., Loher T., Vilar M., Campioni S. In vivo demonstration that alpha-synuclein oligomers are toxic. Proceedings of the National Academy of Sciences 2011, 108:4194-5149.
228. Winner B., Kohl Z., Gage F.H. Neurodegenerative disease and adult neurogenesis. European Journal of Neuroscience 2011, 33:1139-1151.
229. Winner B., Lie D.C., Rockenstein E., Aigner R., Aigner L., Masliah E., Kuhn H.G., Winkler J. Human Wild-Type [alpha]-Synuclein Impairs Neurogenesis. Journal of Neuropathology & Experimental Neurology 2004, 63:1155-1166.
230. Winner B., Melrose H.L., Zhao C., Hinkle K.M., Yue M., Kent C., Braithwaite A.T., Ogholikhan S., Aigner R., Winkler J. Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice. Neurobiology of Disease 2010, 41:706-716.
231. Wolters E.C., Braak H. Parkinson's disease: premotor clinico-pathological correlations. Parkinson's Disease and Related Disorders 2006, 70:309-319.
232. Wong G., Goldshmit Y., Turnley A.M. Interferon-[gamma] but not TNF [alpha] promotes neuronal differentiation and neurite outgrowth of murine adult neural stem cells. Experimental Neurology 2004, 187:171-177.
233. Wu D.C., Jackson-Lewis V., Vila M., Tieu K., Teismann P., Vadseth C., Choi D.K., Ischiropoulos H., Przedborski S. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine mouse model of Parkinson disease. The Journal of Neuroscience 2002, 22:1763-1771.
234. Wynne A.M., Henry C.J., Huang Y., Cleland A., Godbout J.P. Protracted downregulation of CX3CR1 on microglia of aged mice after lipopolysaccharide challenge. Brain, Behavior, and Immunity 2010, 24:1190-1201.
235. Yasuda Y., Shinagawa R., Yamada M., Mori T., Tateishi N., Fujita S. Long-lasting reactive changes observed in microglia in the striatal and substantia nigral of mice after 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Brain Research 2007, 1138:196-202.
236. Yu Z., Xu X., Xiang Z., Zhou J., Zhang Z., Hu C., He C. Nitrated-synuclein induces the loss of dopaminergic neurons in the substantia nigra of rats. PloS One 2010, 5:e9956.
237. Zhang S., Wang X.J., Tian L.P., Pan J., Lu G.Q., Zhang Y.J., Ding J.Q., Chen S.D. CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson's disease. Journal of Neuroinflammation 2011, 8:154-166.
238. Zhang W., Wang T., Pei Z., Miller D.S., Wu X., Block M.L., Wilson B., Zhang W., Zhou Y., Hong J.S. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. The FASEB Journal 2005, 19:533-542.
239. Zhu P., Hata R., Cao F., Gu F., Hanakawa Y., Hashimoto K., Sakanaka M. Ramified microglial cells promote astrogliogenesis and maintenance of neural stem cells through activation of Stat3 function. The FASEB Journal 2008, 22:3866-3877.
240. Ziemssen T., Reichmann H. Non-motor dysfunction in Parkinson's disease. Parkinsonism & Related Disorders 2007, 13:323-332.
241. Zinger A., Barcia C., Herrero M.T., Guillemin G.J. The involvement of neuroinflammation and kynurenine pathway in Parkinson's disease. Human Studies 2011, 10.4061/2011/716859.
242. Ziv Y., Ron N., Butovsky O., Landa G., Sudai E., Greenberg N., Cohen H., Kipnis J., Schwartz M. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nature Neuroscience 2006, 9:268-275.