MAPK signal transduction underlying brain inflammation and gliosis as therapeutic target

Anatomical Record

Volumn 292, Issue 12, 2009, Pages 1902-1913

  Kaminska, Bozena ^a   Gozdz, Agata ^a   Zawadzka, Malgorzata ^a   Ellert Miklaszewska, Aleksandra ^a   Lipko, Maciej ^a  

^a NENCKI INSTITUTE OF EXPERIMENTAL BIOLOGY   (Poland)

Author keywords

AP 1; Brain inflammation; Gliosis; MAP kinases; Microglia activation; Neurodegeneration; NF B; Proinflammatory cytokines; Signal transduction; Small molecule inhibitors; STAT; Toll interleukin 1 receptor superfamily; Transcription factors

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 4 [4 (4 FLUOROPHENYL) 5 (2 METHOXY 4 PYRIMIDINYL) 1 IMIDAZOLYL]CYCLOHEXANOL; ANTHRA[1,9 CD]PYRAZOL 6(2H) ONE; CEP 11004; CEP 1347; CYCLOOXYGENASE 2; CYCLOSPORIN A; DORAMAPIMOD; GAMMA INTERFERON; GLIAL FIBRILLARY ACIDIC PROTEIN; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERFERON REGULATORY FACTOR 3; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 1BETA; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE P38; MYELOID DIFFERENTIATION FACTOR 88; SD 282; SEMAPIMOD; STRESS ACTIVATED PROTEIN KINASE; TACROLIMUS; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR ADAPTOR MOLECULE 2; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; ASTROCYTE; BRAIN INFARCTION SIZE; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; CONFERENCE PAPER; CYTOKINE PRODUCTION; ENDOTOXEMIA; GLIOSIS; GRAFT REJECTION; HUMAN; IMMUNOMODULATION; MICROGLIA; NERVE CELL PLASTICITY; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NEUROPATHY; NEUROPROTECTION; NONHUMAN; OPTIC NERVE INJURY; PARKINSON DISEASE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; SPINAL CORD INJURY; TRANSCRIPTION REGULATION; TRAUMATIC BRAIN INJURY; UPREGULATION;

ADMINISTRATION, ORAL; ANIMALS; ANTI-INFLAMMATORY AGENTS; DISEASE MODELS, ANIMAL; ENCEPHALITIS; ENZYME INHIBITORS; GLIOSIS; HUMANS; MAP KINASE SIGNALING SYSTEM; NEURODEGENERATIVE DISEASES; NEUROGLIA;

ANIMALIA;

EID: 73849096467     PISSN: 19328486     EISSN: 19328494     Source Type: Journal    
DOI: 10.1002/ar.21047     Document Type: Conference Paper

References (104)

1. Aggarwal BB. 2003. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3:745-756.
2. Akira S, Uematsu S, Takeuchi O. 2006. Pathogen recognition and innate immunity. Cell 124:783-801.
3. Aloisi F. 2001. Immune function of microglia. Glia 36:165-179. Badger AM, Bradbeer JN, Votta B, Lee JC, Adams JL, Griswold DE. 1996. Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function. J Pharmacol Exp Ther 279:1453-1461.
4. Bal-Price A, Brown GC. 2001. Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity. J Neurosci 21:6480-6491.
5. Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, Lysko PG, Feuerstein GZ. 1997. Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 28:1233-1244.
6. Barone FC, Irving EA, Ray AM, Lee JC, Kassis S, Kumar S, Badger AM, White RF, McVey MJ, Legos JJ, Erhardt JA, Nelson AH, Ohlstein EH, Hunter AJ, Ward K, Smith BR, Adams JL, Parsons AA. 2001. SB 239063, a second-generation p38 mitogen-activated protein kinase inhibitor, reduces brain injury and neurological deficits in cerebral focal ischemia. J Pharmacol Exp Ther 296:312-321.
7. Basu S, Srivastava PK. 2000. Heat shock proteins: the fountainhead of innate and adaptive immune responses. Cell Stress Chaperones 5:443-451.
8. Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW. 2001. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci USA 98:13681-13686.
9. Benveniste EN. 1998. Cytokine actions in the central nervous system. Cytokine Growth Factor Rev 9:259-275.
10. Bianchi M, Ulrich P, Bloom O, Meistrell M, III, Zimmerman GA, Schmidtmayerova H, Bukrinsky M, Donnelley T, Bucala R, Sherry B, et al. 1995. An inhibitor of macrophage arginine transport and nitric oxide production (CNI-1493) prevents acute inflammation and endotoxin lethality. Mol Med 1:254-266.
11. Block ML, Hong JS. 2005. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76:77-98.
12. Bonizzi G, Karin M. 2004. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 25:280-288.
13. Boutin H, LeFeuvre RA, Horai R, Asano M, Iwakura Y, Rothwell NJ. 2001. Role of IL-1alpha and IL-1beta in ischemic brain damage. J Neurosci 21:5528-5534.
14. Branger J, van den Blink B, Weijer S, Madwed J, Bos CL, Gupta A, Yong CL, Polmar SH, Olszyna DP, Hack CE, van Deventer SJ, Peppelenbosch MP, van der Poll T. 2002. Anti-inflammatory effects of a p38 mitogen-activated protein kinase inhibitor during human endotoxemia. J Immunol 168:4070-4077.
15. Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S. 2009. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest 119:182-192.
16. Brooks SA, Connolly JE, Rigby WF. 2004. The role of mRNA turnover in the regulation of tristetraprolin expression: evidence for an extracellular signal-regulated kinase-specific, AU-rich element-dependent, autoregulatory pathway. J Immunol 172:7263-7271.
17. Carson MJ, Bilousova TV, Puntambekar SS, Melchior B, Doose JM, Ethell IM. 2007. A rose by any other name? The potential consequences of microglial heterogeneity during CNS health and disease. Neurotherapeutics 4:571-579.
18. Carson MJ, Crane J, Xie AX. 2008. Modeling CNS microglia: the quest to identify predictive models. Drug Discov Today: Dis Models 5:19-25.
19. Cayrol R, Wosik K, Berard JL, Dodelet-Devillers A, Ifergan I, Kebir H, Haqqani AS, Kreymborg K, Krug S, Moumdjian R, Bouthillier A, Becher B, Arbour N, David S, Stanimirovic D, Prat A. 2008. Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nat Immunol 9: 137-145.
20. Chen NJ, Chio II, Lin WJ, Duncan G, Chau H, Katz D, Huang HL, Pike KA, Hao Z, Su YW, Yamamoto K, de Pooter RF, Zuniga-Pflucker JC, Wakeham A, Yeh WC, Mak TW. 2008. Beyond tumor necrosis factor receptor: TRADD signaling in Toll-like receptors. Proc Natl Acad Sci USA 105:12429-12434.
21. Chi H, Barry SP, Roth RJ, Wu JJ, Jones EA, Bennett AM, Flavell RA. 2006. Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses. Proc Natl Acad Sci USA 103:2274-2279.
22. Ciallella JR, Saporito M, Lund S, Leist M, Hasseldam H, McGann N, Smith CS, Bozyczko-Coyne D, Flood DG. 2005. CEP-11004, an inhibitor of the SAPK/JNK pathway, reduces TNF-alpha release from lipopolysaccharide-treated cells and mice. Eur J Pharmacol 515:179-187.
23. Clark A, Dean J, Tudor C, Saklatvala J. 2009. Post-transcriptional gene regulation by MAP kinases via AU-rich elements. Front Biosci 14:847-871.
24. Clark AR, Dean JL, Saklatvala J. 2003. Post-transcriptional regulation of gene expression by mitogen-activated protein kinase p38. FEBS Lett 546:37-44.
25. Cohen PS, Nakshatri H, Dennis J, Caragine T, Bianchi M, Cerami A, Tracey KJ. 1996. CNI-1493 inhibits monocyte/macrophage tumor necrosis factor by suppression of translation efficiency. Proc Natl Acad Sci USA 93:3967-3971.
26. Danton GH, Dietrich WD. 2003. Inflammatory mechanisms after ischemia and stroke. J Neuropathol Exp Neurol 62:127-136.
27. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB. 2005. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752-758.
28. Dudal S, Krzywkowski P, Paquette J, Morissette C, Lacombe D, Tremblay P, Gervais F. 2004. Inflammation occurs early during the Abeta deposition process in TgCRND8 mice. Neurobiol Aging 25:861-871.
29. Eikelenboom P, Veerhuis R, Scheper W, Rozemuller AJ, van Gool WA, Hoozemans JJ. 2006. The significance of neuroinflammation in understanding Alzheimer's disease. J Neural Transm 113:1685-1695.
30. Elward K, Gasque P. 2003. "Eat me" and "don't eat me" signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system. Mol Immunol 40:85-94.
31. Ermolaeva MA, Michallet MC, Papadopoulou N, Utermohlen O, Kranidioti K, Kollias G, Tschopp J, Pasparakis M. 2008. Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIFdependent inflammatory responses. Nat Immunol 9:1037-1046.
32. Falsig J, Porzgen P, Lotharius J, Leist M. 2004. Specific modulation of astrocyte inflammation by inhibition of mixed lineage kinases with CEP-1347. J Immunol 173:2762-2770.
33. Falsig J, Porzgen P, Lund S, Schrattenholz A, Leist M. 2006. The inflammatory transcriptome of reactive murine astrocytes and implications for their innate immune function. J Neurochem 96:893-907.
34. Farina C, Aloisi F, Meinl E. 2007. Astrocytes are active players in cerebral innate immunity. Trends Immunol 28:138-145.
35. Feuerstein GZ, Wang X, Barone FC. 1997. Inflammatory gene expression in cerebral ischemia and trauma. Potential new therapeutic targets. Ann N Y Acad Sci 825:179-193.
36. Gehrmann J, Banati RB, Wiessner C, Hossmann KA, Kreutzberg GW. 1995. Reactive microglia in cerebral ischaemia: an early mediator of tissue damage? Neuropathol Appl Neurobiol 21:277-289.
37. Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, Noelle RJ, Becher B. 2005. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11:328-334.
38. Guo X, Dillman JF, III, Dawson VL, Dawson TM. 2001. Neuroimmunophilins: novel neuroprotective and neuroregenerative targets. Ann Neurol 50:6-16.
39. Hanisch UK, Kettenmann H. 2007. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387-1394.
40. Hitti E, Iakovleva T, Brook M, Deppenmeier S, Gruber AD, Radzioch D, Clark AR, Blackshear PJ, Kotlyarov A, Gaestel M. 2006. Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor mRNA stability and translation mainly by altering tristetraprolin expression, stability, and binding to adenine/uridine-rich element. Mol Cell Biol 26:2399-2407.
41. Hu X, Chen J, Wang L, Ivashkiv LB. 2007. Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation. J Leukoc Biol 82:237-243.
42. Jana M, Palencia CA, Pahan K. 2008. Fibrillar amyloid-beta peptides activate microglia via TLR2: implications for Alzheimer's disease. J Immunol 181:7254-7262.
43. Jander S, Kraemer M, Schroeter M, Witte OW, Stoll G. 1995. Lymphocytic infiltration and expression of intercellular adhesion molecule-1 in photochemically induced ischemia of the rat cortex. J Cereb Blood Flow Metab 15:42-51.
44. Kaminska B. 2005. MAPK signalling pathways as molecular targets for anti-inflammatory therapy-from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta 1754:253-262.
45. Kaminska B, Gaweda-Walerych K, Zawadzka M. 2004. Molecular mechanisms of neuroprotective action of immunosuppressants-facts and hypotheses. J Cell Mol Med 8:45-58.
46. Kaminska B, Swiatek-Machado K. 2008. Targeting signaling pathways with small molecules to treat autoimmune disorders. Exp Rev Clin Immunol 4:93-112.
47. Karin M, Gallagher E. 2009. TNFR signaling: ubiquitin-conjugated TRAFfic signals control stop-and-go for MAPK signaling complexes. Immunol Rev 228:225-240.
48. Kilic U, Kilic E, Matter CM, Bassetti CL, Hermann DM. 2008. TLR-4 deficiency protects against focal cerebral ischemia and axotomy-induced neurodegeneration. Neurobiol Dis 31:33-40.
49. Koistinaho M, Kettunen MI, Goldsteins G, Keinanen R, Salminen A, Ort M, Bures J, Liu D, Kauppinen RA, Higgins LS, Koistinaho J. 2002. Beta-amyloid precursor protein transgenic mice that harbor diffuse A beta deposits but do not form plaques show increased ischemic vulnerability: role of inflammation. Proc Natl Acad Sci USA 99:1610-1615.
50. Koistinaho M, Koistinaho J. 2005. Interactions between Alzheimer's disease and cerebral ischemia-focus on inflammation. Brain Res Brain Res Rev 48:240-250.
51. Kotlyarov A, Neininger A, Schubert C, Eckert R, Birchmeier C, Volk HD, Gaestel M. 1999. MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis. Nat Cell Biol 1:94-97.
52. Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, McNulty D, Blumenthal MJ, Heys JR, Landvatter SW, et al. 1994. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 372:739-746.
53. Legos JJ, Erhardt JA, White RF, Lenhard SC, Chandra S, Parsons AA, Tuma RF, Barone FC. 2001. SB 239063, a novel p38 inhibitor, attenuates early neuronal injury following ischemia. Brain Res 892:70-77.
54. Lehnardt S, Lehmann S, Kaul D, Tschimmel K, Hoffmann O, Cho S, Krueger C, Nitsch R, Meisel A, Weber JR. 2007. Toll-like receptor 2 mediates CNS injury in focal cerebral ischemia. J Neuroimmunol 190:28-33.
55. Li X, Massa PE, Hanidu A, Peet GW, Aro P, Savitt A, Mische S, Li J, Marcu KB. 2002. IKKalpha, IKKbeta, and NEMO/IKKgamma are each required for the NF-kappa B-mediated inflammatory response program. J Biol Chem 277:45129-45140.
56. Li X, Qin J. 2005. Modulation of Toll-interleukin 1 receptor mediated signaling. J Mol Med 83:258-266.
57. Liao G, Zhang M, Harhaj EW, Sun SC. 2004. Regulation of the NFkappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J Biol Chem 279:26243-26250.
58. Lund S, Porzgen P, Mortensen AL, Hasseldam H, Bozyczko-Coyne D, Morath S, Hartung T, Bianchi M, Ghezzi P, Bsibsi M, Dijkstra S, Leist M. 2005. Inhibition of microglial inflammation by the MLK inhibitor CEP-1347. J Neurochem 92:1439-1451.
59. Maroney AC, Finn JP, Connors TJ, Durkin JT, Angeles T, Gessner G, Xu Z, Meyer SL, Savage MJ, Greene LA, Scott RW, Vaught JL. 2001. Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J Biol Chem 276:25302-25308.
60. Martinon F, Tschopp J. 2005. NLRs join TLRs as innate sensors of pathogens. Trends Immunol 26:447-454.
61. Matsuzawa A, Tseng PH, Vallabhapurapu S, Luo JL, Zhang W, Wang H, Vignali DA, Gallagher E, Karin M. 2008. Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science 321:663-668.
62. McDonald DR, Bamberger ME, Combs CK, Landreth GE. 1998. beta-amyloid fibrils activate parallel mitogen-activated protein kinase pathways in microglia and THP1 monocytes. J Neurosci 18:4451-4460.
63. McGeer EG, McGeer PL. 2003. Inflammatory processes in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 27:741-749.
64. McGeer PL, McGeer EG. 2004. Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci 1035:104-116.
65. Morioka T, Kalehua AN, Streit WJ. 1993. Characterization of microglial reaction after middle cerebral artery occlusion in rat brain. J Comp Neurol 327:123-132.
66. Nadareishvili ZG, Li H, Wright V, Maric D, Warach S, Hallenbeck JM, Dambrosia J, Barker JL, Baird AE. 2004. Elevated proinflammatory CD4+CD28-lymphocytes and stroke recurrence and death. Neurology 63:1446-1451.
67. Nathan C. 2002. Points of control in inflammation. Nature 420:846-852.
68. Neininger A, Kontoyiannis D, Kotlyarov A, Winzen R, Eckert R, Volk HD, Holtmann H, Kollias G, Gaestel M. 2002. MK2 targets AU-rich elements and regulates biosynthesis of tumor necrosis factor and interleukin-6 independently at different post-transcriptional levels. J Biol Chem 277:3065-3068.
69. Ohsawa K, Irino Y, Nakamura Y, Akazawa C, Inoue K, Kohsaka S. 2007. Involvement of P2X4 and P2Y12 receptors in ATP-induced microglial chemotaxis. Glia 55:604-616.
70. Olson JK, Miller SD. 2004. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol 173:3916-3924.
71. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH. 2001. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22:153-183.
72. Pekny M, Nilsson M. 2005. Astrocyte activation and reactive gliosis. Glia 50:427-434.
73. Petrova TV, Akama KT, Van Eldik LJ. 1999. Selective modulation of BV-2 microglial activation by prostaglandin E(2). Differential effects on endotoxin-stimulated cytokine induction. J Biol Chem 274:28823-28827.
74. Piao CS, Kim JB, Han PL, Lee JK. 2003. Administration of the p38 MAPK inhibitor SB 203580 affords brain protection with a wide therapeutic window against focal ischemic insult. J Neurosci Res 73:537-544.
75. Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A. 2007. Neuroinflammation in Alzheimer's disease and Parkinson's disease: are microglia pathogenic in either disorder? Int Rev Neurobiol 82:235-246.
76. Rothwell N. 2003. Interleukin-1 and neuronal injury: mechanisms, modification, and therapeutic potential. Brain Behav Immun 17:152-157.
77. Rothwell NJ, Luheshi GN. 2000. Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci 23:618-625.
78. Saporito MS, Brown EM, Miller MS, Carswell S. 1999. CEP-1347/ KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons in vivo. J Pharmacol Exp Ther 288:421-427.
79. Scaffidi P, Misteli T, Bianchi ME. 2002. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191-195.
80. Schielke GP, Yang GY, Shivers BD, Betz AL. 1998. Reduced ischemic brain injury in interleukin-1 beta converting enzyme-deficient mice. J Cereb Blood Flow Metab 18:180-185.
81. Schroeter M, Jander S, Witte OW, Stoll G. 1994. Local immune responses in the rat cerebral cortex after middle cerebral artery occlusion. J Neuroimmunol 55:195-203.
82. Schwartz M, London A, Shechter R. 2009. Boosting T-cell immunity as a therapeutic approach for neurodegenerative conditions: the role of innate immunity. Neuroscience 158:1133-1142.
83. Shohami E, Ginis I, Hallenbeck JM. 1999. Dual role of tumor necrosis factor alpha in brain injury. Cytokine Growth Factor Rev 10:119-130.
84. Simi A, Tsakiri N, Wang P, Rothwell NJ. 2007. Interleukin-1 and inflammatory neurodegeneration. Biochem Soc Trans 35:1122-1126.
85. Solt LA, Madge LA, Orange JS, May MJ. 2007. Interleukin-1-induced NF-kappaB activation is NEMO-dependent but does not require IKKbeta. J Biol Chem 282:8724-8733.
86. Steinhoff M, Vergnolle N, Young SH, Tognetto M, Amadesi S, Ennes HS, Trevisani M, Hollenberg MD, Wallace JL, Caughey GH, Mitchell SE, Williams LM, Geppetti P, Mayer EA, Bunnett NW. 2000. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med 6:151-158.
87. Stoll G, Jander S, Schroeter M. 1998. Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 56:149-171.
88. Sugino T, Nozaki K, Takagi Y, Hattori I, Hashimoto N, Moriguchi T, Nishida E. 2000. Activation of mitogen-activated protein kinases after transient forebrain ischemia in gerbil hippocampus. J Neurosci 20:4506-4514.
89. Tang SC, Arumugam TV, Xu X, Cheng A, Mughal MR, Jo DG, Lathia JD, Siler DA, Chigurupati S, Ouyang X, Magnus T, Camandola S, Mattson MP. 2007. Pivotal role for neuronal Tolllike receptors in ischemic brain injury and functional deficits. Proc Natl Acad Sci USA 104:13798-13803.
90. Taylor DL, Diemel LT, Cuzner ML, Pocock JM. 2002. Activation of group II metabotropic glutamate receptors underlies microglial reactivity and neurotoxicity following stimulation with chromogranin A, a peptide up-regulated in Alzheimer's disease. J Neurochem 82:1179-1191.
91. Taylor DL, Jones F, Kubota ES, Pocock JM. 2005. Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor alpha-induced neurotoxicity in concert with microglial-derived Fas ligand. J Neurosci 25:2952-2964.
92. Uematsu S, Akira S. 2007. Toll-like receptors and type I interferons. J Biol Chem 282:15319-15323.
93. Van Eldik LJ, Thompson WL, Ralay Ranaivo H, Behanna HA, Martin Watterson D. 2007. Glia proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: function-based and target-based discovery approaches. Int Rev Neurobiol 82:277-296.
94. Wadsworth SA, Cavender DE, Beers SA, Lalan P, Schafer PH, Malloy EA, Wu W, Fahmy B, Olini GC, Davis JE, Pellegrino-Gensey JL, Wachter MP, Siekierka JJ. 1999. RWJ 67657, a potent, orally active inhibitor of p38 mitogen-activated protein kinase. J Pharmacol Exp Ther 291:680-687.
95. Whitmarsh AJ. 2007. Regulation of gene transcription by mitogenactivated protein kinase signaling pathways. Biochim Biophys Acta 1773:1285-1298.
96. Whitton PS. 2007. Inflammation as a causative factor in the aetiology of Parkinson's disease. Br J Pharmacol 150:963-976.
97. Wisniewski HM, Wegiel J. 1994. The role of microglia in amyloid fibril formation. Neuropathol Appl Neurobiol 20:192-194.
98. Wu H, Arron JR. 2003. TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology. Bioessays 25:1096-1105.
99. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, Akira S. 2003. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301:640-643.
100. Yang SH, Sharrocks AD, Whitmarsh AJ. 2003. Transcriptional regulation by the MAP kinase signaling cascades. Gene 320:3-21.
101. Yilmaz G, Arumugam TV, Stokes KY, Granger DN. 2006. Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation 113:2105-2112.
102. Zawadzka M, Kaminska B. 2005. A novel mechanism of FK506-mediated neuroprotection: downregulation of cytokine expression in glial cells. Glia 49:36-51.
103. Zhu W, Downey JS, Gu J, Di Padova F, Gram H, Han J. 2000. Regulation of TNF expression by multiple mitogen-activated protein kinase pathways. J Immunol 164:6349-6358.
104. Zinser E, Turza N, Steinkasserer A. 2004. CNI-1493 mediated suppression of dendritic cell activation in vitro and in vivo. Immunobiology 209:89-97.