A friend in need may not be a friend indeed: Role of microglia in neurodegenerative diseases

CNS and Neurological Disorders - Drug Targets

Volumn 12, Issue 6, 2013, Pages 726-740

  Kaushik, Deepak Kumar ^a   Basu, Anirban ^a  

^a NATIONAL BRAIN RESEARCH CENTRE   (India)

Author keywords

Alzheimer's disease; Central nervous system; Cytokines; Microglia; Neuroinflammation; Parkinson's disease; Tolllike receptors

Indexed keywords

ACETYLSALICYLIC ACID; ALPHA SYNUCLEIN; AMYLOID BETA PROTEIN; BENZODIAZEPINE RECEPTOR; C REACTIVE PROTEIN; COPPER ZINC SUPEROXIDE DISMUTASE; CYCLOOXYGENASE 2; DEXAMETHASONE; GAMMA INTERFERON; GRANULOCYTE COLONY STIMULATING FACTOR; IBUPROFEN; INDOMETACIN; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; LIPOPOLYSACCHARIDE; MINOCYCLINE; MONOCYTE CHEMOTACTIC PROTEIN 1; NAPROXEN; NEUROMELANIN; PIOGLITAZONE; PROSTAGLANDIN; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; UNINDEXED DRUG; VASCULAR CELL ADHESION MOLECULE 1;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; DEGENERATIVE DISEASE; DISEASE SEVERITY; FLOW CYTOMETRY; HUMAN; HUNTINGTON CHOREA; IMMUNIZATION; IMMUNOHISTOCHEMISTRY; LASER MICROSCOPY; LEWY BODY; MENINGOENCEPHALITIS; MICROGLIA; MULTIPLE SCLEROSIS; NERVE DEGENERATION; NONHUMAN; PARKINSON DISEASE; PHAGOCYTOSIS; POSITRON EMISSION TOMOGRAPHY; REVIEW; RISK FACTOR; TISSUE TRANSPLANTATION;

ALZHEIMER DISEASE; ANIMALS; BRAIN; HUMANS; INFLAMMATION MEDIATORS; MICROGLIA; MULTIPLE SCLEROSIS; NEURODEGENERATIVE DISEASES; PARKINSON DISEASE;

EID: 84888034614     PISSN: 18715273     EISSN: 19963181     Source Type: Journal    
DOI: 10.2174/18715273113126660170     Document Type: Review

References (186)

1. Billingham, R.E.; Boswell, T. Studies on the problem of corneal homografts. Proc. R. Soc. Lond. B. Biol. Sci., 1953, 141(904), 392-406.
2. Medawar, P.B. Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br. J. Exp. Pathol., 1948, 29(1), 58-69.
3. del Rio-Hortega P. In: Penfield, W., Ed.; Cytology and cellular pathology of the nervous system. Hoebaer, P.B.; New York, N.Y. Microglia. 1932, pp. 483-534.
4. Richardson, A.; Hao, C.; Fedoroff, S. Microglia progenitor cells: a subpopulation in cultures of mouse neopallial astroglia. Glia, 1993, 7(1), 25-33.
5. Ling, E.A.; Wong, W.C. The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. Glia, 1993, 7(1), 9-18.
6. Hanisch, U.K. Microglia as a source and target of cytokines. Glia, 2002, 40(2), 140-155.
7. Streit, W.J.; Walter, S.A.; Pennell, N.A. Reactive microgliosis. Prog. Neurobiol., 1999, 57(6), 563-581.
8. Venero, J.L.; Burguillos, M.A.; Brundin, P.; Joseph, B. The executioners sing a new song: killer caspases activate microglia. Cell Death Differ., 2011, 18(11), 1679-1691.
9. McGeer, P.L.; Kawamata, T.; Walker, D.G.; Akiyama, H.; Tooyama, I.; McGeer, E.G. Microglia in degenerative neurological disease. Glia, 1993, 7(1), 84-92.
10. Hickey, W.F.; Kimura, H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science, 1988, 239(4837), 290-292.
11. Matsumoto, Y.; Fujiwara, M. In situ detection of class I and II major histocompatibility complex antigens in the rat central nervous system during experimental allergic encephalomyelitis. An immunohistochemical study. J. Neuroimmunol., 1986, 12(4), 265-277.
12. Kim, S.U.; de Vellis, J. Microglia in health and disease. J. Neurosci. Res., 2005, 81(3), 302-313.
13. Hanke, M.L.; Kielian, T. Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin. Sci. (Lond.), 2011, 121(9), 367-387.
14. Kaushik, D.K.; Gupta, M.; Kumawat, K.L.; Basu, A. NLRP3 inflammasome: key mediator of neuroinflammation in murine Japanese encephalitis. PLoS One, 2012, 7(2), e32270.
15. Jha, S.; Srivastava, S.Y.; Brickey, W.J.; Iocca, H.; Toews, A.; Morrison, J.P.; Chen, V.S.; Gris, D.; Matsushima, G.K.; Ting, J.P. The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J. Neurosci., 2010, 30(47), 15811-15820.
16. Kim, Y.S.; Kim, S.S.; Cho, J.J.; Choi, D.H.; Hwang, O.; Shin, D.H.; Chun, H.S.; Beal, M.F.; Joh, T.H. Matrix metalloproteinase-3: a novel signaling proteinase from apoptotic neuronal cells that activates microglia. J. Neurosci., 2005, 25(14), 3701-3711.
17. Wilms, H.; Rosenstiel, P.; Sievers, J.; Deuschl, G.; Zecca, L.; Lucius, R. Activation of microglia by human neuromelanin is NFkappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson's disease. FASEB J., 2003, 17(3), 500-502.
18. Tran, H.T.; LaFerla, F.M.; Holtzman, D.M.; Brody, D.L. Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute intra-axonal amyloid-beta accumulation and independently accelerates the development of tau abnormalities. J. Neurosci., 2011, 31(26), 9513-9525.
19. Kaisho, T.; Akira, S. Critical roles of Toll-like receptors in host defense. Crit. Rev. Immunol., 2000, 20(5), 393-405.
20. Chakraborty, S.; Kaushik, D.K.; Gupta, M.; Basu, A. Inflammasome signaling at the heart of central nervous system pathology. J. Neurosci. Res., 2010, 88(8), 1615-1631.
21. Kanneganti, T.D.; Body-Malapel, M.; Amer, A.; Park, J.H.; Whitfield, J.; Franchi, L.; Taraporewala, Z.F.; Miller, D.; Patton, J.T.; Inohara, N.; Nunez, G. Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and doublestranded RNA. J. Biol. Chem., 2006, 281(48), 36560-36568.
22. Kaushik, D.K.; Gupta, M.; Basu, A. Microglial response to viral challenges: every silver lining comes with a cloud. Front. Biosci., 2011, 17, 2187-2205.
23. Kaushik, D.K.; Gupta, M.; Das, S.; Basu, A. Kruppel-like factor 4, a novel transcription factor regulates microglial activation and subsequent neuroinflammation. J. Neuroinflammation, 2010, 7, 68.
24. Kaushik, D.K.; Mukhopadhyay, R.; Kumawat, K.L.; Gupta, M.; Basu, A. Therapeutic targeting of Kruppel-like factor 4 abrogates microglial activation. J. Neuroinflammation, 2012, 9, 57.
25. Badiola, N.; Malagelada, C.; Llecha, N.; Hidalgo, J.; Comella, J.X.; Sabria, J.; Rodriguez-Alvarez, J. Activation of caspase-8 by tumour necrosis factor receptor 1 is necessary for caspase-3 activation and apoptosis in oxygen-glucose deprived cultured cortical cells. Neurobiol. Dis., 2009, 35(3), 438-447.
26. Huang, Y.; Erdmann, N.; Peng, H.; Zhao, Y.; Zheng, J. The role of TNF related apoptosis-inducing ligand in neurodegenerative diseases. Cell Mol. Immunol., 2005, 2(2), 113-122.
27. Eugenin, E.A.; Berman, J.W. Chemokine-dependent mechanisms of leukocyte trafficking across a model of the blood-brain barrier. Methods, 2003, 29(4), 351-361.
28. Akira, S.; Taga, T.; Kishimoto, T. Interleukin-6 in biology and medicine. Adv. Immunol., 1993, 54, 1-78.
29. Iadecola, C.; Zhang, F. Permissive and obligatory roles of NO in cerebrovascular responses to hypercapnia and acetylcholine. Am. J. Physiol., 1996, 271(4 Pt 2), R990-R1001.
30. Block, M.L.; Zecca, L.; Hong, J.S. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci., 2007, 8(1), 57-69.
31. Pathak, S.K.; Bhattacharyya, A.; Pathak, S.; Basak, C.; Mandal, D.; Kundu, M.; Basu, J. Toll-like receptor 2 and mitogen-and stressactivated kinase 1 are effectors of Mycobacterium avium-induced cyclooxygenase-2 expression in macrophages. J. Biol. Chem., 2004, 279(53), 55127-55136.
32. Herschman, H.R. Prostaglandin synthase 2. Biochim. Biophys. Acta, 1996, 1299(1), 125-140.
33. Zhao, J.; O'Connor, T.; Vassar, R. The contribution of activated astrocytes to Abeta production: implications for Alzheimer's disease pathogenesis. J. Neuroinflammation, 2011, 8, 150.
34. Meyer-Luehmann, M.; Spires-Jones, T.L.; Prada, C.; Garcia-Alloza, M.; de Calignon, A.; Rozkalne, A.; Koenigsknecht-Talboo, J.; Holtzman, D.M.; Bacskai, B.J.; Hyman, B.T. Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature, 2008, 451(7179), 720-724.
35. Simard, A.R.; Soulet, D.; Gowing, G.; Julien, J.P.; Rivest, S. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron, 2006, 49(4), 489-502.
36. Barger, S.W.; Harmon, A.D. Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature, 1997, 388(6645), 878-881.
37. Neniskyte, U.; Neher, J.J.; Brown, G.C. Neuronal death induced by nanomolar amyloid beta is mediated by primary phagocytosis of neurons by microglia. J. Biol. Chem., 2011, 286(46), 39904-39913.
38. Lautner, R.; Mattsson, N.; Scholl, M.; Augutis, K.; Blennow, K.; Olsson, B.; Zetterberg, H. Biomarkers for microglial activation in Alzheimer's disease. Int. J. Alzheimers Dis., 2011, 2011, 939426.
39. Westin, K.; Buchhave, P.; Nielsen, H.; Minthon, L.; Janciauskiene, S.; Hansson, O. CCL2 is associated with a faster rate of cognitive decline during early stages of Alzheimer's disease. PLoS One, 2012, 7(1), e30525.
40. Rubio-Perez, J.M.; Morillas-Ruiz, J.M. A review: inflammatory process in Alzheimer's disease, role of cytokines. Sci. World J., 2012, 2012, 756357.
41. Meda, L.; Baron, P.; Prat, E.; Scarpini, E.; Scarlato, G.; Cassatella, M.A.; Rossi, F. Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with betaamyloid[25-35]. J. Neuroimmunol., 1999, 93(1-2), 45-52.
42. Halle, A.; Hornung, V.; Petzold, G.C.; Stewart, C.R.; Monks, B.G.; Reinheckel, T.; Fitzgerald, K.A.; Latz, E.; Moore, K.J.; Golenbock, D.T. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat. Immunol., 2008, 9(8), 857-865.
43. Song, M.; Jin, J.; Lim, J.E.; Kou, J.; Pattanayak, A.; Rehman, J.A.; Kim, H.D.; Tahara, K.; Lalonde, R.; Fukuchi, K. TLR4 mutation reduces microglial activation, increases Abeta deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's disease. J. Neuroinflammation, 2011, 8, 92.
44. Tahara, K.; Kim, H.D.; Jin, J.J.; Maxwell, J.A.; Li, L.; Fukuchi, K. Role of toll-like receptor signalling in Abeta uptake and clearance. Brain, 2006, 129(Pt 11), 3006-3019.
45. Liu, S.; Liu, Y.; Hao, W.; Wolf, L.; Kiliaan, A.J.; Penke, B.; Rube, C.E.; Walter, J.; Heneka, M.T.; Hartmann, T.; Menger, M.D.; Fassbender, K. TLR2 is a primary receptor for Alzheimer's amyloid beta peptide to trigger neuroinflammatory activation. J. Immunol., 2012, 188(3), 1098-1107.
46. Hoozemans, J.J.; Rozemuller, A.J.; van Haastert, E.S.; Eikelenboom, P.; van Gool, W.A. Neuroinflammation in Alzheimer's disease wanes with age. J. Neuroinflammation, 2011, 8, 171.
47. Varnum, M.M.; Ikezu, T. The Classification of Microglial Activation Phenotypes on Neurodegeneration and Regeneration in Alzheimer's Disease Brain. Arch. Immunol. Ther. Exp. (Warsz.), 2012, 60(4), 251-266.
48. Johnson, V.E.; Stewart, W.; Smith, D.H. Traumatic brain injury and amyloid-beta pathology: a link to Alzheimer's disease? Nat. Rev. Neurosci., 2010, 11(5), 361-370.
49. Lye, T.C.; Shores, E.A. Traumatic brain injury as a risk factor for Alzheimer's disease: a review. Neuropsychol. Rev., 2000, 10(2), 115-129.
50. Mannix, R.C.; Whalen, M.J. Traumatic brain injury, microglia, and Beta amyloid. Int. J. Alzheimers Dis., 2012, 2012, 608732.
51. Streit, W.J. Microglia and Alzheimer's disease pathogenesis. J. Neurosci. Res., 2004, 77(1), 1-8.
52. Lee, D.C.; Rizer, J.; Selenica, M.L.; Reid, P.; Kraft, C.; Johnson, A.; Blair, L.; Gordon, M.N.; Dickey, C.A.; Morgan, D. LPSinduced inflammation exacerbates phospho-tau pathology in rTg4510 mice. J. Neuroinflammation, 2010, 7, 56.
53. Kitazawa, M.; Oddo, S.; Yamasaki, T.R.; Green, K.N.; LaFerla, F.M. Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's disease. J. Neurosci., 2005, 25(39), 8843-8853.
54. Herber, D.L.; Mercer, M.; Roth, L.M.; Symmonds, K.; Maloney, J.; Wilson, N.; Freeman, M.J.; Morgan, D.; Gordon, M.N. Microglial activation is required for Abeta clearance after intracranial injection of lipopolysaccharide in APP transgenic mice. J. Neuroimmune Pharmacol., 2007, 2(2), 222-231.
55. Fassbender, K.; Walter, S.; Kuhl, S.; Landmann, R.; Ishii, K.; Bertsch, T.; Stalder, A.K.; Muehlhauser, F.; Liu, Y.; Ulmer, A.J.; Rivest, S.; Lentschat, A.; Gulbins, E.; Jucker, M.; Staufenbiel, M.; Brechtel, K.; Walter, J.; Multhaup, G.; Penke, B.; Adachi, Y.; Hartmann, T.; Beyreuther, K. The LPS receptor (CD14) links innate immunity with Alzheimer's disease. FASEB J., 2004, 18(1), 203-205.
56. Liu, Y.; Walter, S.; Stagi, M.; Cherny, D.; Letiembre, M.; Schulz-Schaeffer, W.; Heine, H.; Penke, B.; Neumann, H.; Fassbender, K. LPS receptor (CD14): a receptor for phagocytosis of Alzheimer's amyloid peptide. Brain, 2005, 128(Pt 8), 1778-1789.
57. Shi, J.Q.; Shen, W.; Chen, J.; Wang, B.R.; Zhong, L.L.; Zhu, Y.W.; Zhu, H.Q.; Zhang, Q.Q.; Zhang, Y.D.; Xu, J. Anti-TNF-alpha reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Brain Res., 2011, 1368, 239-247.
58. Montgomery, S.L.; Mastrangelo, M.A.; Habib, D.; Narrow, W.C.; Knowlden, S.A.; Wright, T.W.; Bowers, W.J. Ablation of TNFRI/ RII expression in Alzheimer's disease mice leads to an unexpected enhancement of pathology: implications for chronic pan-TNF-alpha suppressive therapeutic strategies in the brain. Am. J. Pathol., 2011, 179(4), 2053-2070.
59. Bard, F.; Cannon, C.; Barbour, R.; Burke, R.L.; Games, D.; Grajeda, H.; Guido, T.; Hu, K.; Huang, J.; Johnson-Wood, K.; Khan, K.; Kholodenko, D.; Lee, M.; Lieberburg, I.; Motter, R.; Nguyen, M.; Soriano, F.; Vasquez, N.; Weiss, K.; Welch, B.; Seubert, P.; Schenk, D.; Yednock, T. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat. Med., 2000, 6(8), 916-919.
60. Orgogozo, J.M.; Gilman, S.; Dartigues, J.F.; Laurent, B.; Puel, M.; Kirby, L.C.; Jouanny, P.; Dubois, B.; Eisner, L.; Flitman, S.; Michel, B.F.; Boada, M.; Frank, A.; Hock, C. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology, 2003, 61(1), 46-54.
61. Schenk, D. Amyloid-beta immunotherapy for Alzheimer's disease: the end of the beginning. Nat. Rev. Neurosci., 2002, 3(10), 824-828.
62. Gelinas, D.S.; DaSilva, K.; Fenili, D.; St George-Hyslop, P.; McLaurin, J. Immunotherapy for Alzheimer's disease. Proc. Natl. Acad. Sci. USA, 2004, 101(Suppl 2), 14657-14662.
63. Varvel, N.H.; Bhaskar, K.; Kounnas, M.Z.; Wagner, S.L.; Yang, Y.; Lamb, B.T.; Herrup, K. NSAIDs prevent, but do not reverse, neuronal cell cycle reentry in a mouse model of Alzheimer disease. J. Clin. Invest., 2009, 119(12), 3692-3702.
64. Yan, Q.; Zhang, J.; Liu, H.; Babu-Khan, S.; Vassar, R.; Biere, A.L.; Citron, M.; Landreth, G. Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer's disease. J. Neurosci., 2003, 23(20), 7504-7509.
65. Gelb, D.J.; Oliver, E.; Gilman, S. Diagnostic criteria for Parkinson disease. Arch. Neurol., 1999, 56(1), 33-39.
66. Jankovic, J. Parkinson's disease: clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry, 2008, 79(4), 368-376.
67. Samii, A.; Nutt, J.G.; Ransom, B.R. Parkinson's disease. Lancet, 2004, 363(9423), 1783-1793.
68. Long-Smith, C.M.; Sullivan, A.M.; Nolan, Y.M. The influence of microglia on the pathogenesis of Parkinson's disease. Prog. Neurobiol., 2009, 89(3), 277-287.
69. 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(8), 1285-1291.
70. Caballol, N.; Marti, M.J.; Tolosa, E. Cognitive dysfunction and dementia in Parkinson disease. Mov. Disord., 2007, 22(Suppl 17), S358-S366.
71. Spillantini, M.G.; Schmidt, M.L.; Lee, V.M.; Trojanowski, J.Q.; Jakes, R.; Goedert, M. Alpha-synuclein in Lewy bodies. Nature, 1997, 388(6645), 839-840.
72. Zhang, W.; Wang, T.; Pei, Z.; Miller, D.S.; Wu, X.; Block, M.L.; Wilson, B.; Zhang, W.; Zhou, Y.; Hong, J.S.; Zhang, J. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB J., 2005, 19(6), 533-542.
73. Alvarez-Erviti, L.; Couch, Y.; Richardson, J.; Cooper, J.M.; Wood, M.J. Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line. Neurosci. Res., 2011, 69(4), 337-342.
74. 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. Front. Neurosci., 2011, 5, 80.
75. Stefanova, N.; Fellner, L.; Reindl, M.; Masliah, E.; Poewe, W.; Wenning, G.K. Toll-like receptor 4 promotes alpha-synuclein clearance and survival of nigral dopaminergic neurons. Am. J. Pathol., 2011, 179(2), 954-963.
76. McGeer, P.L.; McGeer, E.G. Glial cell reactions in neurodegenerative diseases: pathophysiology and therapeutic interventions. Alzheimer Dis. Assoc. Disord., 1998, 12(Suppl 2), S1-S6.
77. 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. Neurobiol. Dis., 2006, 21(2), 404-412.
78. Ogata, A.; Tashiro, K.; Nukuzuma, S.; Nagashima, K.; Hall, W.W. A rat model of Parkinson's disease induced by Japanese encephalitis virus. J. Neurovirol., 1997, 3(2), 141-147.
79. Ling, Z.; Gayle, D.A.; Ma, S.Y.; Lipton, J.W.; Tong, C.W.; Hong, J.S.; Carvey, P.M. In utero bacterial endotoxin exposure causes loss of tyrosine hydroxylase neurons in the postnatal rat midbrain. Mov. Disord., 2002, 17(1), 116-124.
80. Ling, Z.D.; Chang, Q.; Lipton, J.W.; Tong, C.W.; Landers, T.M.; Carvey, P.M. Combined toxicity of prenatal bacterial endotoxin exposure and postnatal 6-hydroxydopamine in the adult rat midbrain. Neuroscience, 2004, 124(3), 619-628.
81. Hernandez-Romero, M.C.; Delgado-Cortes, M.J.; Sarmiento, M.; de Pablos, R.M.; Espinosa-Oliva, A.M.; Arguelles, S.; Bandez, M.J.; Villaran, R.F.; Maurino, R.; Santiago, M.; Venero, J.L.; Herrera, A.J.; Cano, J.; Machado, A. Peripheral inflammation increases the deleterious effect of CNS inflammation on the nigrostriatal dopaminergic system. Neurotoxicology, 2012, 33(3), 347-360.
82. Langston, J.W.; Forno, L.S.; Tetrud, J.; Reeves, A.G.; Kaplan, J.A.; Karluk, D. 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., 1999, 46(4), 598-605.
83. Hunot, S.; Boissiere, F.; Faucheux, B.; Brugg, B.; Mouatt-Prigent, A.; Agid, Y.; Hirsch, E.C. Nitric oxide synthase and neuronal vulnerability in Parkinson's disease. Neuroscience, 1996, 72(2), 355-363.
84. Knott, C.; Stern, G.; Wilkin, G.P. Inflammatory regulators in Parkinson's disease: iNOS, lipocortin-1, and cyclooxygenases-1 and-2. Mol. Cell Neurosci., 2000, 16(6), 724-739.
85. Kurkowska-Jastrzebska, I.; Litwin, T.; Joniec, I.; Ciesielska, A.; Przybylkowski, A.; Czlonkowski, A.; Czlonkowska, A. Dexamethasone protects against dopaminergic neurons damage in a mouse model of Parkinson's disease. Int. Immunopharmacol., 2004, 4(10-11), 1307-1318.
86. Kurkowska-Jastrzebska, I.; Babiuch, M.; Joniec, I.; Przybylkowski, A.; Czlonkowski, A.; Czlonkowska, A. Indomethacin protects against neurodegeneration caused by MPTP intoxication in mice. Int. Immunopharmacol., 2002, 2(8), 1213-1218.
87. Carrasco, E.; Werner, P. Selective destruction of dopaminergic neurons by low concentrations of 6-OHDA and MPP+: protection by acetylsalicylic acid aspirin. Parkinsonism Relat. Disord., 2002, 8(6), 407-411.
88. Casper, D.; Yaparpalvi, U.; Rempel, N.; Werner, P. Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro. Neurosci. Lett., 2000, 289(3), 201-204.
89. Grilli, M.; Pizzi, M.; Memo, M.; Spano, P. Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation. Science, 1996, 274(5291), 1383-1385.
90. Thomas, M.; Le, W.D. Minocycline: neuroprotective mechanisms in Parkinson's disease. Curr. Pharm. Des., 2004, 10(6), 679-686.
91. Tsuji, M.; Wilson, M.A.; Lange, M.S.; Johnston, M.V. Minocycline worsens hypoxic-ischemic brain injury in a neonatal mouse model. Exp. Neurol., 2004, 189(1), 58-65.
92. Diguet, E.; Gross, C.E.; Tison, F.; Bezard, E. Rise and fall of minocycline in neuroprotection: need to promote publication of negative results. Exp. Neurol., 2004, 189(1), 1-4.
93. Qian, L.; Hong, J.S.; Flood, P.M. Role of microglia in inflammation-mediated degeneration of dopaminergic neurons: neuroprotective effect of interleukin 10. J. Neural Transm. Suppl., 2006, (70), 367-371.
94. Johnston, L.C.; Su, X.; Maguire-Zeiss, K.; Horovitz, K.; Ankoudinova, I.; Guschin, D.; Hadaczek, P.; Federoff, H.J.; Bankiewicz, K.; Forsayeth, J. Human interleukin-10 gene transfer is protective in a rat model of Parkinson's disease. Mol. Ther., 2008, 16(8), 1392-1399.
95. Group THsDCR. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell, 1993, 72(6), 971-983.
96. Sotrel, A.; Paskevich, P.A.; Kiely, D.K.; Bird, E.D.; Williams, R.S.; Myers, R.H. Morphometric analysis of the prefrontal cortex in Huntington's disease. Neurology, 1991, 41(7), 1117-1123.
97. Diaz-Hernandez, M.; Diez-Zaera, M.; Sanchez-Nogueiro, J.; Gomez-Villafuertes, R.; Canals, J.M.; Alberch, J.; Miras-Portugal, M.T.; Lucas, J.J. Altered P2X7-receptor level and function in mouse models of Huntington's disease and therapeutic efficacy of antagonist administration. FASEB J., 2009, 23(6), 1893-1906.
98. Lobsiger, C.S.; Cleveland, D.W. Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease. Nat. Neurosci., 2007, 10(11), 1355-1360.
99. McGeer, P.L.; McGeer, E.G.; Itagaki, S.; Mizukawa, K. Anatomy and pathology of the basal ganglia. Can. J. Neurol. Sci., 1987, 14(3 Suppl), 363-372.
100. von Bernhardi, R.; Tichauer, J.E.; Eugenin, J. Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders. J. Neurochem., 2010, 112(5), 1099-1114.
101. Ma, L.; Morton, A.J.; Nicholson, L.F. Microglia density decreases with age in a mouse model of Huntington's disease. Glia, 2003, 43(3), 274-280.
102. Simmons, D.A.; Casale, M.; Alcon, B.; Pham, N.; Narayan, N.; Lynch, G. Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington's disease. Glia, 2007, 55(10), 1074-1084.
103. Kraft, A.D.; Kaltenbach, L.S.; Lo, D.C.; Harry, G.J. Activated microglia proliferate at neurites of mutant huntingtin-expressing neurons. Neurobiol. Aging, 2012, 33(3), e17-e33.
104. Singhrao, S.K.; Neal, J.W.; Morgan, B.P.; Gasque, P. Increased complement biosynthesis by microglia and complement activation on neurons in Huntington's disease. Exp. Neurol., 1999, 159(2), 362-376.
105. Bjorkqvist, M.; Wild, E.J.; Thiele, J.; Silvestroni, A.; Andre, R.; Lahiri, N.; Raibon, E.; Lee, R.V.; Benn, C.L.; Soulet, D.; Magnusson, A.; Woodman, B.; Landles, C.; Pouladi, M.A.; Hayden, M.R.; Khalili-Shirazi, A.; Lowdell, M.W.; Brundin, P.; Bates, G.P.; Leavitt, B.R.; Moller, T.; Tabrizi, S.J. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. J. Exp. Med., 2008, 205(8), 1869-1877.
106. Pavese, N.; Gerhard, A.; Tai, Y.F.; Ho, A.K.; Turkheimer, F.; Barker, R.A.; Brooks, D.J.; Piccini, P. Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology, 2006, 66(11), 1638-1643.
107. Tai, Y.F.; Pavese, N.; Gerhard, A.; Tabrizi, S.J.; Barker, R.A.; Brooks, D.J.; Piccini, P. Microglial activation in presymptomatic Huntington's disease gene carriers. Brain, 2007, 130(Pt 7), 1759-1766.
108. Tai, Y.F.; Pavese, N.; Gerhard, A.; Tabrizi, S.J.; Barker, R.A.; Brooks, D.J.; Piccini, P. Imaging microglial activation in Huntington's disease. Brain Res. Bull., 2007, 72(2-3), 148-151.
109. Politis, M.; Pavese, N.; Tai, Y.F.; Kiferle, L.; Mason, S.L.; Brooks, D.J.; Tabrizi, S.J.; Barker, R.A.; Piccini, P. Microglial activation in regions related to cognitive function predicts disease onset in Huntington's disease: a multimodal imaging study. Hum. Brain Mapp., 2011, 32(2), 258-270.
110. Topper, R.; Gehrmann, J.; Schwarz, M.; Block, F.; Noth, J.; Kreutzberg, G.W. Remote microglial activation in the quinolinic acid model of Huntington's disease. Exp. Neurol., 1993, 123(2), 271-283.
111. Ryu, J.K.; Choi, H.B.; McLarnon, J.G. Peripheral benzodiazepine receptor ligand PK11195 reduces microglial activation and neuronal death in quinolinic acid-injected rat striatum. Neurobiol. Dis., 2005, 20(2), 550-561.
112. Ryu, J.K.; Kim, S.U.; McLarnon, J.G. Blockade of quinolinic acidinduced neurotoxicity by pyruvate is associated with inhibition of glial activation in a model of Huntington's disease. Exp. Neurol., 2004, 187(1), 150-159.
113. Chen, M.; Ona, V.O.; Li, M.; Ferrante, R.J.; Fink, K.B.; Zhu, S.; Bian, J.; Guo, L.; Farrell, L.A.; Hersch, S.M.; Hobbs, W.; Vonsattel, J.P.; Cha, J.H.; Friedlander, R.M. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat. Med., 2000, 6(7), 797-801.
114. Palazuelos, J.; Aguado, T.; Pazos, M.R.; Julien, B.; Carrasco, C.; Resel, E.; Sagredo, O.; Benito, C.; Romero, J.; Azcoitia, I.; Fernandez-Ruiz, J.; Guzman, M.; Galve-Roperh, I. Microglial CB2 cannabinoid receptors are neuroprotective in Huntington's disease excitotoxicity. Brain, 2009, 132(Pt 11), 3152-3164.
115. Zhang, Y.; Friedlander, R.M. Using non-coding small RNAs to develop therapies for Huntington's disease. Gene Ther., 2011, 18(12), 1139-1149.
116. Freeman, T.B.; Cicchetti, F.; Hauser, R.A.; Deacon, T.W.; Li, X.J.; Hersch, S.M.; Nauert, G.M.; Sanberg, P.R.; Kordower, J.H.; Saporta, S.; Isacson, O. Transplanted fetal striatum in Huntington's disease: phenotypic development and lack of pathology. Proc. Natl. Acad. Sci. USA, 2000, 97(25), 13877-13882.
117. Boillee, S.; Yamanaka, K.; Lobsiger, C.S.; Copeland, N.G.; Jenkins, N.A.; Kassiotis, G.; Kollias, G.; Cleveland, D.W. Onset and progression in inherited ALS determined by motor neurons and microglia. Science, 2006, 312(5778), 1389-1392.
118. Monk, P.N.; Shaw, P.J. ALS: life and death in a bad neighborhood. Nat. Med., 2006, 12(8), 885-887.
119. Sargsyan, S.A.; Monk, P.N.; Shaw, P.J. Microglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis. Glia, 2005, 51(4), 241-253.
120. Rosen, D.R.; Siddique, T.; Patterson, D.; Figlewicz, D.A.; Sapp, P.; Hentati, A.; Donaldson, D.; Goto, J.; O'Regan, J.P.; Deng, H.X. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature, 1993, 362(6415), 59-62.
121. Gowing, G.; Philips, T.; Van Wijmeersch, B.; Audet, J.N.; Dewil, M.; Van Den Bosch, L.; Billiau, A.D.; Robberecht, W.; Julien, J.P. Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase. J. Neurosci., 2008, 28(41), 10234-1044.
122. Dibaj, P.; Steffens, H.; Zschuntzsch, J.; Nadrigny, F.; Schomburg, E.D.; Kirchhoff, F.; Neusch, C. In Vivo imaging reveals distinct inflammatory activity of CNS microglia versus PNS macrophages in a mouse model for ALS. PLoS One, 2011, 6(3), e17910.
123. Meissner, F.; Molawi, K.; Zychlinsky, A. Mutant superoxide dismutase 1-induced IL-1beta accelerates ALS pathogenesis. Proc. Natl. Acad. Sci. USA, 2010, 107(29), 13046-13050.
124. Yoshihara, T.; Ishigaki, S.; Yamamoto, M.; Liang, Y.; Niwa, J.; Takeuchi, H.; Doyu, M.; Sobue, G. Differential expression of inflammation-and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem., 2002, 80(1), 158-167.
125. Moreau, C.; Devos, D.; Brunaud-Danel, V.; Defebvre, L.; Perez, T.; Destee, A.; Tonnel, A.B.; Lassalle, P.; Just, N. Elevated IL-6 and TNF-alpha levels in patients with ALS: inflammation or hypoxia? Neurology, 2005, 65(12), 1958-1960.
126. Poloni, M.; Facchetti, D.; Mai, R.; Micheli, A.; Agnoletti, L.; Francolini, G.; Mora, G.; Camana, C.; Mazzini, L.; Bachetti, T. Circulating levels of tumour necrosis factor-alpha and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis. Neurosci. Lett., 2000, 287(3), 211-214.
127. Hensley, K.; Fedynyshyn, J.; Ferrell, S.; Floyd, R.A.; Gordon, B.; Grammas, P.; Hamdheydari, L.; Mhatre, M.; Mou, S.; Pye, Q.N.; Stewart, C.; West, M.; West, S.; Williamson, K.S. Message and protein-level elevation of tumor necrosis factor alpha (TNF alpha) and TNF alpha-modulating cytokines in spinal cords of the G93ASOD1 mouse model for amyotrophic lateral sclerosis. Neurobiol. Dis., 2003, 14(1), 74-80.
128. Henkel, J.S.; Beers, D.R.; Zhao, W.; Appel, S.H. Microglia in ALS: the good, the bad, and the resting. J. Neuroimmune Pharmacol., 2009, 4(4), 389-398.
129. Sta, M.; Sylva-Steenland, R.M.; Casula, M.; de Jong, J.M.; Troost, D.; Aronica, E.; Baas, F. Innate and adaptive immunity in amyotrophic lateral sclerosis: evidence of complement activation. Neurobiol. Dis., 2011, 42(3), 211-220.
130. Chiu, I.M.; Chen, A.; Zheng, Y.; Kosaras, B.; Tsiftsoglou, S.A.; Vartanian, T.K.; Brown, R.H., Jr.; Carroll, M.C. T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS. Proc. Natl. Acad. Sci. USA, 2008, 105(46), 17913-17918.
131. Kuhle, J.; Lindberg, R.L.; Regeniter, A.; Mehling, M.; Steck, A.J.; Kappos, L.; Czaplinski, A. Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis. Eur. J. Neurol., 2009, 16(6), 771-774.
132. Henkel, J.S.; Engelhardt, J.I.; Siklos, 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. Ann. Neurol., 2004, 55(2), 221-235.
133. Wilms, H.; Sievers, J.; Dengler, R.; Bufler, J.; Deuschl, G.; Lucius, R. Intrathecal synthesis of monocyte chemoattractant protein-1 (MCP-1) in amyotrophic lateral sclerosis: further evidence for microglial activation in neurodegeneration. J. Neuroimmunol., 2003, 144(1-2), 139-142.
134. Rentzos, M.; Nikolaou, C.; Rombos, A.; Boufidou, F.; Zoga, M.; Dimitrakopoulos, A.; Tsoutsou, A.; Vassilopoulos, D. RANTES levels are elevated in serum and cerebrospinal fluid in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler., 2007, 8(5), 283-287.
135. Liang, X.; Wang, Q.; Shi, J.; Lokteva, L.; Breyer, R.M.; Montine, T.J.; Andreasson, K. The prostaglandin E2 EP2 receptor accelerates disease progression and inflammation in a model of amyotrophic lateral sclerosis. Ann. Neurol., 2008, 64(3), 304-314.
136. Almer, G.; Teismann, P.; Stevic, Z.; Halaschek-Wiener, J.; Deecke, L.; Kostic, V.; Przedborski, S. Increased levels of the proinflammatory prostaglandin PGE2 in CSF from ALS patients. Neurology, 2002, 58(8), 1277-1279.
137. Pompl, P.N.; Ho, L.; Bianchi, M.; McManus, T.; Qin, W.; Pasinetti, G.M. A therapeutic role for cyclooxygenase-2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis. FASEB J., 2003, 17(6), 725-727.
138. Schutz, B.; Reimann, J.; Dumitrescu-Ozimek, L.; Kappes-Horn, K.; Landreth, G.E.; Schurmann, B.; Zimmer, A.; Heneka, M.T. The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. J. Neurosci., 2005, 25(34), 7805-7812.
139. Van Den Bosch, L.; Tilkin, P.; Lemmens, G.; Robberecht, W. Minocycline delays disease onset and mortality in a transgenic model of ALS. Neuroreport, 2002, 13(8), 1067-1070.
140. Kriz, J.; Nguyen, M.D.; Julien, J.P. Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol. Dis., 2002, 10(3), 268-278.
141. Gordon, P.H.; Moore, D.H.; Miller, R.G.; Florence, J.M.; Verheijde, J.L.; Doorish, C.; Hilton, J.F.; Spitalny, G.M.; MacArthur, R.B.; Mitsumoto, H.; Neville, H.E.; Boylan, K.; Mozaffar, T.; Belsh, J.M.; Ravits, J.; Bedlack, R.S.; Graves, M.C.; McCluskey, L.F.; Barohn, R.J.; Tandan, R. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol., 2007, 6(12), 1045-1053.
142. Pollari, E.; Savchenko, E.; Jaronen, M.; Kanninen, K.; Malm, T.; Wojciechowski, S.; Ahtoniem, T.; Goldsteins, G.; Giniatullina, R.; Giniatullin, R.; Koistinaho, J.; Magga, J. Granulocyte colony stimulating factor attenuates inflammation in a mouse model of amyotrophic lateral sclerosis. J. Neuroinflammation, 2011, 8, 74.
143. Carson, M.J. Microglia as liaisons between the immune and central nervous systems: functional implications for multiple sclerosis. Glia, 2002, 40(2), 218-231.
144. Eng, L.F.; Ghirnikar, R.S.; Lee, Y.L. Inflammation in EAE: role of chemokine/cytokine expression by resident and infiltrating cells. Neurochem. Res., 1996, 21(4), 511-525.
145. Steinman, L. Multiple sclerosis: a two-stage disease. Nat. Immunol., 2001, 2(9), 762-764.
146. Kanwar, J.R. Anti-inflammatory immunotherapy for multiple sclerosis/experimental autoimmune encephalomyelitis (EAE) disease. Curr. Med. Chem., 2005, 12(25), 2947-2962.
147. Rus, H.; Cudrici, C.; Niculescu, F.; Shin, M.L. Complement activation in autoimmune demyelination: dual role in neuroinflammation and neuroprotection. J. Neuroimmunol., 2006, 180(1-2), 9-16.
148. Ajami, B.; Bennett, J.L.; Krieger, C.; McNagny, K.M.; Rossi, F.M. Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat. Neurosci., 2011, 14(9), 1142-1149.
149. Williams, K.C.; Ulvestad, E.; Hickey, W.F. Immunology of multiple sclerosis. Clin. Neurosci., 1994, 2(3-4), 229-245.
150. Henderson, A.P.; Barnett, M.H.; Parratt, J.D.; Prineas, J.W. Multiple sclerosis: distribution of inflammatory cells in newly forming lesions. Ann. Neurol., 2009, 66(6), 739-753.
151. McMahon, E.J.; Bailey, S.L.; Castenada, C.V.; Waldner, H.; Miller, S.D. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat. Med., 2005, 11(3), 335-339.
152. Jack, C.; Ruffini, F.; Bar-Or, A.; Antel, J.P. Microglia and multiple sclerosis. J. Neurosci. Res., 2005, 81(3), 363-373.
153. Heppner, F.L.; Greter, M.; Marino, D.; Falsig, J.; Raivich, G.; Hovelmeyer, N.; Waisman, A.; Rulicke, T.; Prinz, M.; Priller, J.; Becher, B.; Aguzzi, A. Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nat. Med., 2005, 11(2), 146-152.
154. Napoli, I.; Neumann, H. Protective effects of microglia in multiple sclerosis. Exp. Neurol., 2010, 225(1), 24-28.
155. Huizinga, R.; van der Star, B.J.; Kipp, M.; Jong, R.; Gerritsen, W.; Clarner, T.; Puentes, F.; Dijkstra, C.D.; van der Valk, P.; Amor, S. Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis. Glia, 2012, 60(3), 422-431.
156. Olah, M.; Amor, S.; Brouwer, N.; Vinet, J.; Eggen, B.; Biber, K.; Boddeke, H.W. Identification of a microglia phenotype supportive of remyelination. Glia, 2012, 60(2), 306-321.
157. Haider, L.; Fischer, M.T.; Frischer, J.M.; Bauer, J.; Hoftberger, R.; Botond, G.; Esterbauer, H.; Binder, C.J.; Witztum, J.L.; Lassmann, H. Oxidative damage in multiple sclerosis lesions. Brain, 2011, 134(Pt 7), 1914-1924.
158. Brambilla, R.; Ashbaugh, J.J.; Magliozzi, R.; Dellarole, A.; Karmally, S.; Szymkowski, D.E.; Bethea, J.R. Inhibition of soluble tumour necrosis factor is therapeutic in experimental autoimmune encephalomyelitis and promotes axon preservation and remyelination. Brain, 2011, 134(Pt 9), 2736-2754.
159. Murphy, A.C.; Lalor, S.J.; Lynch, M.A.; Mills, K.H. Infiltration of Th1 and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis. Brain Behav. Immun., 2010, 24(4), 641-651.
160. Quintana, A.; Muller, M.; Frausto, R.F.; Ramos, R.; Getts, D.R.; Sanz, E.; Hofer, M.J.; Krauthausen, M.; King, N.J.; Hidalgo, J.; Campbell, I.L. Site-specific production of IL-6 in the central nervous system retargets and enhances the inflammatory response in experimental autoimmune encephalomyelitis. J. Immunol., 2009, 183(3), 2079-2088.
161. Centonze, D.; Muzio, L.; Rossi, S.; Cavasinni, F.; De Chiara, V.; Bergami, A.; Musella, A.; D'Amelio, M.; Cavallucci, V.; Martorana, A.; Bergamaschi, A.; Cencioni, M.T.; Diamantini, A.; Butti, E.; Comi, G.; Bernardi, G.; Cecconi, F.; Battistini, L.; Furlan, R.; Martino, G. Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis. J. Neurosci., 2009, 29(11), 3442-3452.
162. Farez, M.F.; Quintana, F.J.; Gandhi, R.; Izquierdo, G.; Lucas, M.; Weiner, H.L. Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE. Nat. Immunol., 2009, 10(9), 958-964.
163. van Loo, G.; De Lorenzi, R.; Schmidt, H.; Huth, M.; Mildner, A.; Schmidt-Supprian, M.; Lassmann, H.; Prinz, M.R.; Pasparakis, M. Inhibition of transcription factor NF-kappaB in the central nervous system ameliorates autoimmune encephalomyelitis in mice. Nat. Immunol., 2006, 7(9), 954-961.
164. Ramaglia, V.; Hughes, T.R.; Donev, R.M.; Ruseva, M.M.; Wu, X.; Huitinga, I.; Baas, F.; Neal, J.W.; Morgan, B.P. C3-dependent mechanism of microglial priming relevant to multiple sclerosis. Proc. Natl. Acad. Sci. USA, 2012, 109(3), 965-970.
165. Mills, J.H.; Kim, D.G.; Krenz, A.; Chen, J.F.; Bynoe, M.S. A2A adenosine receptor signaling in lymphocytes and the central nervous system regulates inflammation during experimental autoimmune encephalomyelitis. J. Immunol., 2012, 188(11), 5713-5722.
166. Gris, D.; Ye, Z.; Iocca, H.A.; Wen, H.; Craven, R.R.; Gris, P.; Huang, M.; Schneider, M.; Miller, S.D.; Ting, J.P. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J. Immunol., 2010, 185(2), 974-981.
167. Ponomarev, E.D.; Veremeyko, T.; Barteneva, N.; Krichevsky, A.M.; Weiner, H.L. MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-alpha-PU.1 pathway. Nat. Med., 2010, 17(1), 64-70.
168. Chechneva, O.V.; Mayrhofer, F.; Daugherty, D.J.; Pleasure, D.E.; Hong, J.S.; Deng, W. Low dose dextromethorphan attenuates moderate experimental autoimmune encephalomyelitis by inhibiting NOX2 and reducing peripheral immune cells infiltration in the spinal cord. Neurobiol. Dis., 2011, 44(1), 63-72.
169. Ratchford, J.N.; Endres, C.J.; Hammoud, D.A.; Pomper, M.G.; Shiee, N.; McGready, J.; Pham, D.L.; Calabresi, P.A. Decreased microglial activation in MS patients treated with glatiramer acetate. J. Neurol., 2012, 259(6), 1199-1205.
170. Gao, Z.; Tsirka, S.E. Animal Models of MS Reveal Multiple Roles of Microglia in Disease Pathogenesis. Neurol. Res. Int., 2012, 2011, 383087.
171. Martin, R.; Hernandez, M.; Cordova, C.; Nieto, M. Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis. Br. J. Pharmacol., 2012, 166(5), 1708-1723.
172. Kihara, Y.; Matsushita, T.; Kita, Y.; Uematsu, S.; Akira, S.; Kira, J.; Ishii, S.; Shimizu, T. Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis. Proc. Natl. Acad. Sci. US A, 2009, 106(51), 21807-21812.
173. Gao, H.M.; Hong, J.S. Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol., 2008, 29(8), 357-365.
174. McGann, J.C.; Lioy, D.T.; Mandel, G. Astrocytes conspire with neurons during progression of neurological disease. Curr. Opin. Neurobiol., 2012.
175. Bessis, A.; Bechade, C.; Bernard, D.; Roumier, A. Microglial control of neuronal death and synaptic properties. Glia, 2007, 55(3), 233-238.
176. Nakajima, K.; Kikuchi, Y.; Ikoma, E.; Honda, S.; Ishikawa, M.; Liu, Y.; Kohsaka, S. Neurotrophins regulate the function of cultured microglia. Glia, 1998, 24(3), 272-289.
177. Butovsky, O.; Ziv, Y.; Schwartz, A.; Landa, G.; Talpalar, A.E.; Pluchino, S.; Martino, G.; Schwartz, M. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol. Cell Neurosci., 2006, 31(1), 149-160.
178. Politis, M.; Su, P.; Piccini, P. Imaging of microglia in patients with neurodegenerative disorders. Front. Pharmacol., 2012, 3, 96.
179. Wilms, H.; Claasen, J.; Rohl, C.; Sievers, J.; Deuschl, G.; Lucius, R. Involvement of benzodiazepine receptors in neuroinflammatory and neurodegenerative diseases: evidence from activated microglial cells in vitro. Neurobiol. Dis., 2003, 14(3), 417-424.
180. Kaur, C.; Ling, E.A. Antioxidants and neuroprotection in the adult and developing central nervous system. Curr. Med. Chem., 2008, 15(29), 3068-3080.
181. Liu, B.; Gao, H.M.; Wang, J.Y.; Jeohn, G.H.; Cooper, C.L.; Hong, J.S. Role of nitric oxide in inflammation-mediated neurodegeneration. Ann. NY Acad. Sci., 2002, 962, 318-331.
182. Minones-Moyano, E.; Porta, S.; Escaramis, G.; Rabionet, R.; Iraola, S.; Kagerbauer, B.; Espinosa-Parrilla, Y.; Ferrer, I.; Estivill, X.; Marti, E. MicroRNA profiling of Parkinson's disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function. Hum. Mol. Genet., 2011, 20(15), 3067-3078.
183. Williams, A.H.; Valdez, G.; Moresi, V.; Qi, X.; McAnally, J.; Elliott, J.L.; Bassel-Duby, R.; Sanes, J.R.; Olson, E.N. MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science, 2009, 326(5959), 1549-1554.
184. Murugaiyan, G.; Beynon, V.; Mittal, A.; Joller, N.; Weiner, H.L. Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis. J. Immunol., 2011, 187(5), 2213-2221.
185. Hebert, S.S.; Horre, K.; Nicolai, L.; Papadopoulou, A.S.; Mandemakers, W.; Silahtaroglu, A.N.; Kauppinen, S.; Delacourte, A.; De Strooper, B. Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression. Proc. Natl. Acad. Sci. USA, 2008, 105(17), 6415-6420.
186. Nunez-Iglesias, J.; Liu, C.C.; Morgan, T.E.; Finch, C.E.; Zhou, X.J. Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer's disease cortex reveals altered miRNA regulation. PLoS One, 2010, 5(2), e8898.