Biological role of Toll-like receptor-4 in the brain

Journal of Neuroimmunology

Volumn 268, Issue 1-2, 2014, Pages 1-12

  Trotta, Teresa ^a   Porro, Chiara ^a   Calvello, Rosa ^b   Panaro, Maria Antonietta ^b  

^a UNIVERSITY OF FOGGIA   (Italy)

^b UNIVERSITY OF BARI   (Italy)

Author keywords

Alzheimer; Amyotrophic lateral sclerosis; Inflammation; Multiple sclerosis; Parkinson; TLR 4

Indexed keywords

TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 4 AGONIST; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; BRAIN; DEGENERATIVE DISEASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GENETIC POLYMORPHISM; HUMAN; MULTIPLE SCLEROSIS; NERVE DEGENERATION; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TRAUMATIC BRAIN INJURY;

ALZHEIMER; AMYOTROPHIC LATERAL SCLEROSIS; INFLAMMATION; MULTIPLE SCLEROSIS; PARKINSON; TLR-4;

ANIMALS; BRAIN; HUMANS; NEURODEGENERATIVE DISEASES; TOLL-LIKE RECEPTOR 4;

EID: 84896734547     PISSN: 01655728     EISSN: 18728421     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2014.01.014     Document Type: Review

References (216)

1. Ahmad A., Crupi R., Campolo M., Genovese T., Esposito E., Cuzzocrea S. Absence of TLR4 reduces neurovascular unit and secondary inflammatory process after traumatic brain injury in mice. PLoS One 2013, 8:57208-57220.
2. 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, 14:1142-1149.
3. Akira S., Takeda K. Toll-like receptor signalling. Nat. Rev. Immunol. 2004, 4:499-511.
4. Akira S., Uematsu S., Takeuchi O. Pathogen recognition and innate immunity. Cell 2006, 124:783-801.
5. Al-Chalabi A., Dürr A., Wood N.W., Parkinson M.H., Camuzat A., Hulot J.S., Morrison K.E., Renton A., Sussmuth S.D., Landwehrmeyer B.G., Ludolph A., Agid Y., Brice A., Leigh P.N., Bensimon G., NNIPPS Genetic Study Group Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy. PLoS One 2009, 4:e7114.
6. Alfonso-Loeches S., Pascual-Lucas M., Blanco A.M., Sanchez-Vera I., Guerri C. Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage. J. Neurosci. 2010, 30:8285-8295.
7. Allan S.M., Rothwell N.J. Cytokines and acute neurodegeneration. Nat. Rev. Neurosci. 2001, 2:734-744.
8. Andersson A., Covacu R., Sunnemark D., Danilov A.I., Dal Bianco A., Khademi M., Wallström E., Lobell A., Brundin L., Lassmann H., Harris R.A. Pivotal advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis. J. Leukoc. Biol. 2008, 84:1248-1255.
9. Apetoh L., Ghiringhelli F., Tesniere A., Obeid M., Ortiz C., Criollo A., Mignot G., Maiuri M.C., Ullrich E., Saulnier P., Yang H., Amigorena S., Ryffel B., Barrat F.J., Saftig P., Levi F., Lidereau R., Nogues C., Mira J.P., Chompret A., Joulin V., Clavel-Chapelon F., Bourhis J., André F., Delaloge S., Tursz T., Kroemer G., Zitvogel L. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 2007, 13:1050-1059.
10. Balistreri C.R., Grimaldi M.P., Chiappelli M., Licastro F., Castiglia L., Listì F., Vasto S., Lio D., Caruso C., Candore G. Association between the polymorphisms of TLR4 and CD14 genes and Alzheimer's disease. Curr. Pharm. Des. 2008, 14:2672-2677.
11. Banati R.B., Daniel S.E., Blunt S.B. Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease. Mov. Disord. 1998, 13:221-227.
12. Bar-Shavit Z. Taking a toll on the bones: regulation of bone metabolism by innate immune regulators. Autoimmunity 2008, 41:195-203.
13. Bauer J., Sminia T., Wouterlood F.G., Dijkstra C.D. Phagocytic activity of macrophages and microglial cells during the course of acute and chronic relapsing experimental autoimmune encephalomyelitis. J. Neurosci. Res. 1994, 38:365-375.
14. Beers D.R., Henkel J.S., Xiao Q., Zhao W., Wang J., Yen A.A., Siklos L., McKercher S.R., Appel S.H. Wild-type microGlia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:16021-16026.
15. Belarbi K., Jopson T., Tweedie D., Arellano C., Luo W., Greig N.H., Rosi S. TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation. J. Neuroinflammation 2012, 9:23.
16. Benveniste E.N. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J. Mol. Med. 1997, 75:165-173.
17. Béraud D., Maguire-Zeiss K.A. Misfolded α-synuclein and Toll-like receptors: therapeutic targets for Parkinson's disease. Parkinsonism Relat. Disord. 2012, 18:S17-S20.
18. Beraud D., Twomey M., Bloom B., Mittereder A., Ton V., Neitzke K., Chasovskikh S., Mhyre T.R., Maguire-Zeiss K.A. α-Synuclein alters Toll-like receptor expression. Front. Neurosci. 2011, 5:80.
19. Beutler B., Eidenschenk C., Crozat K., Imler J.L., Takeuchi O., Hoffmann J.A., Akira S. Genetic analysis of resistance to viral infection. Nat. Rev. Immunol. 2007, 7:753-766.
20. Bianchi M.E. DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leukoc. Biol. 2007, 81:1-5.
21. Biragyn A., Ruffini P.A., Leifer C.A., Klyushnenkova E., Shakhov A., Chertov O., Shirakawa A.K., Farber J.M., Segal D.M., Oppenheim J.J., Kwak L.W. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 2002, 298:1025-1029.
22. Biragyn A., Coscia M., Nagashima K., Sanford M., Young H.A., Olkhanud P. Murine beta-defensin 2 promotes TLR- 4/MyD88-mediated and NF-kappaBdependent atypical death of APCs via activation of TNFR2. J. Leukoc. Biol. 2008, 83:998-1008.
23. Blach-Olszewska Z., Leszek J. Mechanisms of over-activated innate immune system regulation in autoimmune and neurodegenerative disorders. Neuropsychiatr. Dis. Treat. 2007, 3:365-372.
24. Blanco A.M., Guerri C. Ethanol intake enhances inflammatory mediators in brain: role of glial cells and TLR4/IL-1RI receptors. Front. Biosci. 2007, 12:2616-2630.
25. Blanco A.M., Vallés S.L., Pascual M., Guerri C. Involvement of TLR4/type I IL-1 receptor signaling in the induction of inflammatory mediators and cell death induced by ethanol in cultured astrocytes. Immunology 2005, 175:6893-6899.
26. Bode J.G., Ehlting C., Häussinger D. The macrophage response towards LPS and its control through the p38(MAPK)-STAT3 axis. Cell. Signal. 2012, 24:1185-1194.
27. Boillée 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, 312:1389-1392.
28. Bowman C.C., Rasley A., Tranguch S.L., Marriott I. Cultured astrocytes express Toll-like receptors for bacterial products. Glia 2003, 43:281-291.
29. Bsibsi M., Ravid R., Gveric D., van Noort J.M. Broad expression of Toll-like receptors in the human central nervous system. J. Neuropathol. Exp. Neurol. 2002, 61:1013-1021.
30. Capiralla H., Vingtdeux V., Zhao H., Sankowski R., Al-Abed Y., Davies P., Marambaud P. Resveratrol mitigates lipopolysaccharide- and Aβ-mediated microglial inflammation by inhibiting the TLR4/NF-κB/STAT signaling cascade. J. Neurochem. 2012, 120:461-472.
31. Carpentier P.A., Begolka W.S., Olson J.K., Elhofy A., Karpus W.J., Miller S.D. Differential activation of astrocytes by innate and adaptive immune stimuli. Glia 2005, 4:360-374.
32. Carty M., Bowie A.G. Evaluating the role of Toll-like receptors in diseases of the central nervous system. Biochem. Pharmacol. 2011, 81:825-837.
33. Caso J.R., Pradillo J.M., Hurtado O., Lorenzo P., Moro M.A., Lizasoain I. Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation 2007, 115:1599-1608.
34. Casula M., Iyer A.M., Spliet W.G., Anink J.J., Steentjes K., Sta M., Troost D., Aronica E. Toll-like receptor signaling in amyotrophic lateral sclerosis spinal cord tissue. Neuroscience 2011, 179:233-243.
35. Chase M.A., Wheeler D.S., Lierl K.M., Hughes V.S., Wong H.R., Page K. Hsp72 induces inflammation and regulates cytokine production in airway epithelium through a TLR4- and NF-kappaB-dependent mechanism. J. Immunol. 2007, 179:6318-6324.
36. Chen L.W., Huang H.L., Lee I.T., Hsu C.M., Lu P.J. Hypertonic saline enhances host defense to bacterial challenge by augmenting Toll-like receptors. Crit. Care Med. 2006, 34:1758-1768.
37. Chen L.W., Huang H.L., Lee I.T., Hsu C.M., Lu P.J. Luteolin suppresses inflammation-associated gene expression by blocking NF-kappaB and AP-1 activation pathway in mouse alveolar macrophages. Life Sci. 2007, 8:1602-1614.
38. Chen G., Shi J., Jin W., Wang L., Xie W., Sun J., Hang C. Progesterone administration modulates TLRs/NF-kappaB signaling pathway in rat brain after cortical contusion. Ann. Clin. Lab. Sci. 2008, 38:65-74.
39. Chen G., Zhang S., Shi J., Ai J., Qi M., Hang C. Simvastatin reduces secondary brain injury caused by cortical contusion in rats: possible involvement of TLR4/NF-kappaB pathway. Exp. Neurol. 2009, 216:398-406.
40. Chen C.C., Hung T.H., Wang Y.H., Lin C.W., Wang P.Y., Lee C.Y., Chen S.F. Wogonin improves histological and functional outcomes, and reduces activation of TLR4/NF-κB signaling after experimental traumatic brain injury. PLoS One 2012, 7:e30294.
41. Chiron D., Bekeredjian-Ding I., Pellat-Deceunynck C., Bataille R., Jego G. Toll-like receptors: lessons to learn from normal and malignant human B cells. Blood 2008, 112:2205-2213.
42. Compston A., Coles A. Multiple sclerosis. Lancet 2008, 372:1502-1517.
43. Constantinescu C.S., Farooqi N., O'Brien K., Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br. J. Pharmacol. 2011, 164:1079-1106.
44. Cookson M.R. α-Synuclein and neuronal cell death. Mol. Neurodegener. 2009, 4:9.
45. Crack P.J., Bray P.J. Toll-like receptors in the brain and their potential roles in neuropathology. Immunol. Cell Biol. 2007, 85:476-480.
46. Crews F.T., Nixon K. Mechanisms of neurodegeneration and regeneration in alcoholism. Alcohol Alcohol. 2009, 44:115-127.
47. Dong C. Regulation and pro-inflammatory function of interleukin-17 family cytokines. Immunol. Rev. 2008, 226:80-86.
48. Dong C., Flavell R.A. Cell fate decision: T-helper 1 and 2 subsets in immune responses. Arthritis Res. 2000, 2:179-188.
49. Dong X.Q., Yu W.H., Hu Y.Y., Zhang Z.Y., Huang M. Oxymatrine reduces neuronal cell apoptosis by inhibiting Toll-like receptor 4/nuclear factor kappa-B-dependent inflammatory responses in traumatic rat brain injury. Inflamm. Res. 2011, 60:533-539.
50. Duttaa G., Zhanga P., Liua B. The lipopolysaccharide Parkinson's disease animal model: mechanistic studies and drug discovery. Fundam. Clin. Pharmacol. 2008, 22:453-464.
51. Ehrchen J.M., Sunderkötter C., Foell D., Vogl T., Roth J. The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. J. Leukoc. Biol. 2009, 86:557-566.
52. Erridge C. Endogenous ligands of TLR2 and TLR4: agonists or assistants?. J. Leukoc. Biol. 2010, 87:989-999.
53. Esen N., Tanga F.Y., DeLeo J.A., Kielian T. Toll-like receptor 2 (TLR2) mediates astrocyte activation in response to the Gram-positive bacterium Staphylococcus aureus. J. Neurochem. 2004, 88:746-758.
54. Falsig J., Latta M., Leist M. Defined inflammatory states in astrocyte cultures: correlation with susceptibility towards CD95-driven apoptosis. J. Neurochem. 2004, 88:181-193.
55. Falsig J., Pörzgen P., Lotharius J., Leist M. Specific modulation of astrocyte inflammation by inhibition of mixed lineage kinases with CEP-1347. J. Immunol. 2004, 173:2762-2770.
56. Farina C., Krumbholz M., Giese T., Hartmann G., Aloisi F., Meinl E. Preferential expression and function of Toll-like receptor 3 in human astrocytes. J. Neuroimmunol. 2005, 159:12-19.
57. Fassbender K., Walter S., Kühl 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, 18:203-205.
58. Fellner L., Irschick R., Schanda K., Reindl M., Klimaschewski L., Poewe W., Wenning G.K., Stefanova N. Toll-like receptor 4 is required for a-synuclein dependent activation of microglia and astroglia. Glia 2013, 61:349-360.
59. Fischer H., Ellström P., Ekström K., Gustafsson L., Gustafsson M., Svanborg C. Ceramide as a TLR4 agonist; a putative signalling intermediate between sphingolipid receptors for microbial ligands and TLR4. Cell. Microbiol. 2007, 9:1239-1251.
60. Flo T.H., Ryan L., Latz E., Takeuchi O., Monks B.G., Lien E., Halaas Ø., Akira S., Skjåk-Braek G., Golenbock D.T., Espevik T. Involvement of Toll-like receptor (TLR) 2 and TLR4 in cell activation by mannuronic acid polymers. J. Biol. Chem. 2002, 277:35489-35495.
61. Frank S., Copanaki E., Burbach G.J., Müller U.C., Deller T. Differential regulation of Toll-like receptor mRNAs in amyloid plaque-associated brain tissue of aged APP23 transgenic mice. Neurosci. Lett. 2009, 453:41-44.
62. Gasser T. Molecular pathogenesis of Parkinson disease: insights from genetic studies. Expert Rev. Mol. Med. 2009, 11:e22.
63. Gay N.J., Gangloff M. Structure and function of Toll receptors and their ligands. Annu. Rev. Biochem. 2007, 76:141-165.
64. Graves M.C., Fiala M., Dinglasan L.A., Liu N.Q., Sayre J., Chiappelli F., van Kooten C., Vinters H.V. Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2004, 5:213-219.
65. Guillot L., Balloy V., McCormack F.X., Golenbock D.T., Chignard M., Si-Tahar M. Cutting edge: the immunostimulatory activity of the lung surfactant protein-A involves toll-like receptor 4. J. Immunol. 2002, 168:5989-5992.
66. Gurney M.E., Liu R., Althaus J.S., Hall E.D., Becker D.A. Mutant CuZn superoxide dismutase in motor neuron disease. J. Inherit. Metab. Dis. 1998, 21:587-597.
67. Hanke M.L., Kielian T. Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin. Sci. 2011, 121:367-387.
68. Harrington L.E., Hatton R.D., Mangan P.R., Turner H., Murphy T.L., Murphy K.M., Weaver C.T. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol. 2005, 6:1123-1132.
69. Hashimoto C., Hudson K.L., Anderson K.V. The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein. Cell 1988, 52:269-279.
70. Heldwein K.A., Liang M.D., Andresen T.K., Thomas K.E., Marty A.M., Cuesta N., Vogel S.N., Fenton M.J. TLR2 and TLR4 serve distinct roles in the host immune response against Mycobacterium bovis BCG. J. Leukoc. Biol. 2003, 74:277-286.
71. 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, 55:221-235.
72. Hodgkinson C.P., Laxton R.C., Patel K., Ye S. Advanced glycation end-product of low density lipoprotein activates the toll-like 4 receptor pathway implications for diabetic atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2008, 28:2275-2281.
73. Holm T.H., Draeby D., Owens T. Microglia are required for astroglial Toll-like receptor 4 response and for optimal TLR2 and TLR3 response. Glia 2012, 60:630-638.
74. Hoshino K., Takeuchi O., Kawai T., Sanjo H., Ogawa T., Takeda Y., Takeda K., Akira S. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps hene product. J. Immunol. 1999, 162:3749-3752.
75. Hua F., Ma J., Ha T., Xia Y., Kelley J., Williams D.L., Kao R.L., Browder I.W., Schweitzer J.B., Kalbfleisch J.H., Li C. Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. J. Neuroimmunol. 2007, 190:101-111.
76. Hyakkoku K., Hamanaka J., Tsuruma K., Shimazawa M., Tanaka H., Uematsu S., Akira S., Inagaki N., Nagai H., Hara H. Toll-like receptor 4 (TLR4), but not TLR3 or TLR9, knock-out mice have neuroprotective effects against focal cerebral ischemia. Neuroscience 2010, 17:258-267.
77. Imai Y., Kuba K., Neely G.G., Yaghubian-Malhami R., Perkmann T., van Loo G., Ermolaeva M., Veldhuizen R., Leung Y.H., Wang H., Liu H., Sun Y., Pasparakis M., Kopf M., Mech C., Bavari S., Peiris J.S., Slutsky A.S., Akira S., Hultqvist M., Holmdahl R., Nicholls J., Jiang C., Binder C.J., Penninger J.M. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 2008, 133:235-249.
78. 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 Neuropathol. 2003, 106:518-526.
79. Iribarren P., Chen K., Hu J., Gong W., Cho E.H., Lockett S., Uranchimeg B., Wang J.M. CpG-containing oligodeoxynucleotide promotes microglial cell uptake of amyloid beta 1-42 peptide by up-regulating the expression of the G-protein-coupled receptor mFPR2. FASEB J. 2005, 19:2032-2034.
80. Jana M., Palencia C.A., Pahan K. Fibrillar amyloid-beta peptides activate microglia via TLR2: implications for Alzheimer's disease. J. Immunol. 2008, 181:7254-7262.
81. Ji Y., Liu J., Wang Z., Lui N. Angiotensin II induces inflammatory response partly via toll-like receptor 4-dependent signaling pathway in vascular smooth muscle cells. Cell. Physiol. Biochem. 2009, 23:265-276.
82. Jiang D., Liang J., Fan J., Yu S., Chen S., Luo Y., Prestwich G.D., Mascarenhas M.M., Garg H.G., Quinn D.A., Homer R.J., Goldstein D.R., Bucala R., Lee P.J., Medzhitov R., Noble P.W. Regulation of lung injury and repair by toll-like receptors and hyaluronan. Nat. Med. 2005, 11:1173-1179.
83. Jin M.S., Lee J.-O. Structures of the Toll-like receptor family and its ligand complexes. Immunity 2008, 29:182-191.
84. Jin J.J., Kim H.D., Maxwell J.A., Li L., Fukuchi K. Toll-like receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer's disease. J. Neuroinflammation 2008, 5:23.
85. Johnson G.B., Brunn G.J., Kodaira Y., Platt J.L. Receptor-mediated monitoring of tissue well-being via detection of soluble heparin sulfate by toll-like receptor 4. J. Immunol. 2002, 168:5233-5239.
86. Kagan J.C., Medzhitovd R. Phosphoinositide mediated adaptor recruitment controls Toll-like receptor signaling. Cell 2006, 125:943-955.
87. Kang J., Rivest S. MyD88-deficient bone marrow cells accelerate onset and reduce survival in a mouse model of amyotrophic lateral sclerosis. J. Cell Biol. 2007, 179:1219-1230.
88. Kerfoot S.M., Long E.M., Hickey M.J., Andonegui G., Lapointe B.M., Zanardo R.C., Bonder C., James W.G., Robbins S.M., Kubes P. TLR4 contributes to disease-inducing mechanisms resulting in central nervous system autoimmune disease. J. Immunol. 2004, 173:7070-7077.
89. Kielian T. Toll-like receptors in central nervous system glial inflammation and homeostasis. J. Neurosci. Res. 2006, 83:711-730.
90. Kim Y.S., Joh T.H. Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease. Exp. Mol. Med. 2006, 38:333-347.
91. Kim W.G., Mohney R.P., Wilson B., Jeohn G.H., Liu B., Hong J.S. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J. Neurosci. 2000, 20:6309-6316.
92. Kinsner A., Pilotto V., Deininger S., Brown G.C., Coecke S., Hartung T., Bal-Price A. Inflammatory neurodegeneration induced by lipoteichoic acid from Staphylococcus aureus is mediated by glia activation, nitrative and oxidative stress, and caspase activation. J. Neurochem. 2005, 95:1132-1143.
93. Koedel U., Merbt U.M., Schmidt C., Angele B., Popp B., Wagner H., Pfister H.W., Kirschning C.J. Acute brain injury triggers MyD88-dependent, TLR2/4-independent inflammatory responses. Am. J. Pathol. 2007, 171:200-213.
94. Lacroix S., Feinstein D., Rivest S. The bacterial endotoxin lipopolysaccharide has the ability to target the brain in upregulating its membrane CD14 receptor within specific cellular populations. Brain Pathol. 1998, 8:625-640.
95. Laflamme N., Rivest S. Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating Gram-negative bacterial cell wall components. FASEB J. 2001, 15:155-163.
96. Lee M.S., Kim Y.J. Signaling pathways downstream of pattern-recognition receptors and their cross talk. Ann. Rev. Biochem. 2007, 76:447-480.
97. Lee J.H., Jung H.S., Giang P.M., Jin X., Lee S., Son P.T., Lee D., Hong Y.S., Lee K., Lee J.J. Blockade of nuclear factor-kappaB signaling pathway and anti-inflammatory activity of cardamomin, a chalcone analog from Alpinia conchigera. J. Pharmacol. Exp. Ther. 2006, 316:271-278.
98. Lees J.R., Golumbek P.T., Sim J., Dorsey D., Russell J.H. Regional CNS responses to IFN-gamma determine lesion localization patterns during EAE pathogenesis. J. Exp. Med. 2008, 205:2633-2642.
99. Lehnardt S., Lachance C., Patrizi S., Lefebvre S., Follett P.L., Jensen F.E., Rosenberg P.A., Volpe J.J., Vartanian T. The Toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J. Neurosci. 2002, 22:2478-2486.
100. Lehnardt S., Massillon L., Follett P., Jensen F.E., Ratan R., Rosenberg P.A., Volpe J.J., Vartanian T. Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:8514-8519.
101. Lemaitre B., Nicolas E., Michaut L., Reichhart J.M., Hoffmann J.A. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996, 86:973-983.
102. Letiembre M., Liu Y., Walter S., Hao W., Pfander T., Wrede A., Schulz-Schaeffer W., Fassbender K. Screening of innate immune receptors in neurodegenerative diseases: a similar pattern. Neurobiol. Aging 2009, 30:759-768.
103. Li Y., Chu N., Hu A., Gran B., Rostami A., Zhang G.X. Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia. Brain 2007, 130:490-501.
104. Liu-Bryan R., Scott P., Sydlaske A., Rose D.M., Terkeltaub R. Innate immunity conferred by toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum. 2005, 52:2936-2946.
105. Liu M., Bing G. Lipopolysaccharide animal models for Parkinson's disease. Parkinsons Dis. 2011, 2011:327089.
106. 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, 128:1778-1789.
107. Liu Y., Hao W., Dawson A., Liu S., Fassbender K. Expression of amyotrophic lateral sclerosis-linked SOD1 mutant increases the neurotoxic potential of microglia via TLR2. J. Biol. Chem. 2009, 284:3691-3699.
108. Lucas S.M., Rothwell N.J., Gibson R.M. The role of inflammation in CNS injury and disease. Br. J. Pharmacol. 2006, 147:S232-S240.
109. Ma Y., Haynes R.L., Sidman R.L., Vartanian T. TLR8: an innate immune receptor in brain, neurons and axons. Cell Cycle 2007, 6:2859-2868.
110. Mallard C., Wang X., Hagberg H. The role of Toll-like receptors in perinatal brain injury. Clin. Perinatol. 2009, 36:763-772.
111. Maroso M., Balosso S., Ravizza T., Liu J., Aronica E., Iyer A.M., Rossetti C., Molteni M., Casalgrandi M., Manfredi A.A., Bianchi M.E., Vezzani A. Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat. Med. 2010, 16:413-419.
112. Marsh B., Stevens S.L., Packard A.E., Gopalan B., Hunter B., Leung P.Y., Harrington C.A., Stenzel-Poore M.P. Systemic lipopolysaccharide protects the brain from ischemic injury by reprogramming the response of the brain to stroke: a critical role for IRF3. J. Neurosci. 2009, 29:9839-9849.
113. Marta M., Andersson A., Isaksson M., Kämpe O., Lobell A. Unexpected regulatory roles of TLR4 and TLR9 in experimental autoimmune encephalomyelitis. Eur. J. Immunol. 2008, 38:565-575.
114. Mazarati A., Maroso M., Iori V., Vezzani A., Carli M. High-mobility group box-1 impairs memory in mice through both Toll-like receptor 4 and receptor for advanced glycation end products. Exp. Neurol. 2011, 232:143-148.
115. 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, 38:1285-1291.
116. McGuire K., Jones M., Werling D., Williams J.L., Glass E.J., Jann O. Radiation hybrid mapping of all 10 characterized bovine Toll-like receptors. Anim. Genet. 2006, 37:47-50.
117. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 2007, 449:819-826.
118. Medzhitov R., Preston-Hurlburt P., Janeway C.A. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997, 388:394-397.
119. Mensah-Brown E.P., Shahin A., Al Shamisi M., Lukic M.L. Early influx of macrophages determines susceptibility to experimental allergic encephalomyelitis in Dark Agouti (DA) rats. J. Neuroimmunol. 2011, 232:68-74.
120. Midwood K., Sacre S., Piccinini A.M., Inglis J., Trebaul A., Chan E., Drexler S., Sofat N., Kashiwagi M., Orend G., Brennan F., Foxwell B. Tenascin-C is an endogenous activator of toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat. Med. 2009, 15:774-780.
121. Miller Y.I. Toll-like receptors and atherosclerosis: oxidized LDL as an endogenous Toll-like receptor ligand. Futur. Cardiol. 2005, 1:785-792.
122. Miller Y.I., Viriyakosol S., Binder C.J. Minimally modified LDL binds to CD14, induces macrophage spreading via TLR4/MD-2, and inhibits phagocytosis of apoptotic cells. J. Biol. Chem. 2003, 278:1561-1568.
123. Minoretti P., Gazzaruso C., Vito C.D., Emanuele E., Bianchi M., Coen E., Reino M., Geroldi D. Effect of the functional Toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer's disease. Neurosci. Lett. 2006, 391:147-149.
124. Mishra B.B., Mishra P.K., Teale J.M. Expression and distribution of Toll-like receptors in the brain during murine neurocysticercosis. J. Neuroimmunol. 2006, 181:46-56.
125. Morales I., Farías G., Maccioni R.B. Neuroimmunomodulation in the pathogenesis of Alzheimer's disease. Neuroimmunomodulation 2010, 17:202-204.
126. Morganti-Kossmann M.C., Rancan M., Stahel P.F., Kossmann T. Inflammatory response in acute traumatic brain injury: a double-edged sword. Curr. Opin. Crit. Care 2002, 8:101-105.
127. Naert G., Laflamme N., Rivest S. Toll-like receptor 2-independent and MyD88-dependent gene expression in the mouse brain. J. Innate Immun. 2009, 1:480-493.
128. Nguyen M.D., D'Aigle T., Gowing G., Julien J.P., Rivest S. Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis. J. Neurosci. 2004, 24:1340-1349.
129. Noreen M., Shah M.A., Mall S.M., Choudhary S., Hussain T., Ahmed I., Jalil S.F., Raza M.I. TLR4 polymorphisms and disease susceptibility. Inflamm. Res. 2012, 61:177-188.
130. Nüsslein-Volhard C., Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature 1980, 287:795-801.
131. Oblak A., Jerala R. Toll-like receptor 4 activation in cancer progression and therapy. Clin. Dev. Immunol. 2011, 2011:609579.
132. Ohashi K., Burkart V., Flohé S., Kolb H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J. Immunol. 2000, 164:558-561.
133. Okamura Y., Watari M., Jerud E.S., Young D.W., Ishizaka S.T., Rose J., Chow J.C., Strauss J.F. The extra domain A of fibronectin activates toll-like receptor 4. J. Biol. Chem. 2001, 276:10229-10233.
134. Okuma Y., Liu K., Wake H., Zhang J., Maruo T., Date I., Yoshino T., Ohtsuka A., Otani N., Tomura S., Shima K., Yamamoto Y., Yamamoto H., Takahashi H.K., Mori S., Nishibori M. Anti-high mobility group box-1 antibody therapy for traumatic brain injury. Ann. Neurol. 2012, 72:373-384.
135. Okun E., Griffioen K.J., Lathia J.D., Tang S.C., Mattson M.P., Arumugam T.V. Toll-like receptors in neurodegeneration. Brain Res. Rev. 2009, 59:278-292.
136. Olson J.K., Miller S.D. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J. Immunol. 2004, 173:3916-3924.
137. O'Neill L.A., Dinarello C.A. The IL-1 receptor/Toll-like receptor superfamily: crucial receptors for inflammation and host defense. Immunol. Today 2000, 21:206-209.
138. Orange J.S., Geha R.S. Finding NEMO: genetic disorders of NF-[kappa]B activation. J. Clin. Invest. 2003, 112:983-985.
139. Panaro M.A., Cianciulli A. Current opinions and perspectives on the role of immune system in the pathogenesis of Parkinson's disease. Curr. Pharm. Des. 2012, 18:200-208.
140. Panaro M.A., Lofrumento D.D., Saponaro C., De Nuccio F., Cianciulli A., Mitolo V., Nicolardi G. Expression of TLR4 and CD14 in the central nervous system (CNS) in a MPTP mouse model of Parkinson's-like disease. Immunopharmacol. Immunotoxicol. 2008, 30:729-740.
141. Parajuli B., Sonobe Y., Kawanokuchi J., Doi Y., Noda M., Takeuchi H., Mizuno T., Suzumura A. GM-CSF increases LPS-induced production of proinflammatory mediators via upregulation of TLR4 and CD14 in murine microglia. J. Neuroinflammation 2012, 9:268.
142. Park H.D., Lee Y., Oh Y.K., Jung J.G., Park Y.W., Myung K., Kim K.H., Koh S.S., Lim D.S. Pancreatic adenocarcinoma upregulated factor promotes metastasis by regulating TLR/CXCR4 activation. Oncogene 2011, 30:201-211.
143. Park H., Li Z., Yang X.O., Chang S.H., Nurieva R., Wang Y.H., Wang Y., Hood L., Zhu Z., Tian Q., Dong C. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 2005, 6:1133-1141.
144. Park J.S., Svetkauskaite D., He Q., Kim J.Y., Strassheim D., Ishizaka A., Abraham E. Involvement of toll like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J. Biol. Chem. 2004, 279:7370-7377.
145. Poltorak A., He X., Smirnova I., Liu M.Y., Van Huffel C., Du X., Birdwell D., Alejos E., Silva M., Galanos C., Freudenberg M., Ricciardi-Castagnoli P., Layton B., Beutler B. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutation in Tlr4 gene. Science 1998, 282:2085-2088.
146. Poltorak A., Ricciardi-Castagnoli P., Citterio S., Beutler B. Physical contact between lipopolysaccharide and Toll-like receptor 4 revealed by genetic complementation. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:2163-2167.
147. Prehaud C., Megret F., Lafage M., Lafon M. Virus infection switches TLR-3-positive human neurons to become strong producers of beta interferon. J. Virol. 2005, 79:12893-12904.
148. Puel A., Picard C., Ku C.L., Smahi A., Casanova J.L. Inherited disorders of NF-kappaB-mediated immunity in man. Curr. Opin. Immunol. 2004, 16:34-41.
149. Qin L., Li G., Qian X., Liu Y., Wu X., Liu B., Hong J.S., Block M.L. Interactive role of the toll like receptor 4 and reactive oxygen species in LPS-induced microglia activation. Glia 2005, 52:78-84.
150. Racke M.K., Drew P.D. Toll-like receptors in multiple sclerosis. Curr. Top. Microbiol. Immunol. 2009, 336:155-168.
151. Rauvala H., Rouhiainen A. Physiological and pathophysiological outcomes of the interactions of HMGB1 with cell surface receptors. Biochim. Biophys. Acta 2010, 1799:164-170.
152. Reed-Geaghan E.G., Savage J.C., Hise A.G., Landreth G.E. CD14 and Toll-like receptors 2 and 4 are required for fibrillar A{beta}-stimulated microglial activation. J. Neurosci. 2009, 29:11982-11989.
153. Reynolds J.M., Martinez G.J., Chung Y., Dong C. Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation. Proc. Natl. Acad. Sci. U. S. A. 2012, 109:13064-13069.
154. Rivest S. Regulation of innate immuneresponses in the brain. Nat. Rev. Immunol. 2009, 9:429-439.
155. Roelofs M.F., Boelens W.C., Joosten L.A., Abdollahi-Roodsaz S., Geurts J., Wunderink L.U., Schreurs B.W., van den Berg W.B., Radstake T.R. Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J. Immunol. 2006, 176:7021-7027.
156. Rolls A., Shechter R., London A., Ziv Y., Ronen A., Levy R., Schwartz M. Toll-like receptors modulate adult hippocampal neurogenesis. Nat. Cell Biol. 2007, 9:1081-1088.
157. 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.
158. Sandri S., Rodriguez D., Gomes E., Monteiro H.P., Russo M., Campa A. Is serum amyloid A an endogenous TLR4 agonist?. J. Leukoc. Biol. 2008, 83:1174-1180.
159. Schaefer L., Babelova A., Kiss E., Hausser H.J., Baliova M., Krzyzankova M., Marsche G., Young M.F., Mihalik D., Götte M., Malle E., Schaefer R.M., Gröne H.J. The matrix component biglycan is proinflammatory and signals through toll-like receptors 4 and 2 in macrophages. J. Clin. Invest 2005, 115:2223-2233.
160. Scholz S.W., Houlden H., Schulte C., Sharma M., Li A., Berg D., Melchers A., Paudel R., Gibbs J.R., Simon-Sanchez J., Paisan-Ruiz C., Bras J., Ding J., Chen H., Traynor B.J., Arepalli S., Zonozi R.R., Revesz T., Holton J., Wood N., Lees A., Oertel W., Wüllner U., Goldwurm S., Pellecchia M.T., Illig T., Riess O., Fernandez H.H., Rodriguez R.L., Okun M.S., Poewe W., Wenning G.K., Hardy J.A., Singleton A.B., Del Sorbo F., Schneider S., Bhatia K.P., Gasser T. SNCA variants are associated with increased risk for multiple system atrophy. Ann. Neurol. 2009, 65:610-614.
161. Schröder N.W., Schumann R.R. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect. Dis. 2005, 5:156-164.
162. Shi H., Kokoeva M.V., Inouye K., Tzameli I., Yin H., Flier J.S. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 2006, 116:3015-3025.
163. Shichita T., Sakaguchi R., Suzuki M., Yoshimura A. Post-ischemic inflammation in the brain. Front. Immunol. 2012, 3:132.
164. Shults C.W., Rockenstein E., Crews L., Adame A., Mante M., Larrea G., Hashimoto M., Song D., Iwatsubo T., Tsuboi K., Masliah E. Neurological and neurodegenerative alterations in a transgenic mouse model expressing human alpha-synuclein under oligodendrocyte promoter: implications for multiple system atrophy. J. Neurosci. 2005, 25:10689-10699.
165. Smiley S.T., King J.A., Hancock W.W. Fibrinogen stimulates macrophagechemokine secretion through toll-like receptor 4. J. Immunol. 2001, 167:2887-2894.
166. Smirnova I., Hamblin M.T., McBride C., Beutler B., Di Rienzo A. Excess of rare amino acid polymorphisms in the Toll-like receptor 4 in humans. Genetics 2001, 158:1657-1664.
167. Sola C., Casal C., Tusell J.M., Serratosa J. Astrocytes enhance lipopolysaccharide induced nitric oxide production by microglial cells. Eur. J. Neurosci. 2002, 16:1275-1283.
168. 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 Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's disease. J. Neuroinflammation 2011, 8:92.
169. Stefanova N., Reindl M., Neumann M., Kahle P.J., Poewe W., Wenning G.K. Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy. Mov. Disord. 2007, 22:2196-2203.
170. Stefanova N., Fellner L., Reindl M., Masliah E., Poewe W., Wenning G.K. Toll-like receptor 4 promotes α-synuclein clearance and survival of nigral dopaminergic neurons. Am. J. Pathol. 2011, 179:954-963.
171. Steward R., McNally F.J., Schedl P. Isolation of the dorsal locus of Drosophila. Nature 1984, 311:262-265.
172. Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A., Rayner K.J., Boyer L., Zhong R., Frazier W.A., Lacy-Hulbert A., El Khoury J., Golenbock D.T., Moore K.J. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat. Immunol. 2010, 11:155-161.
173. Su X., Wang H., Zhao J., Pan H., Mao L. Beneficial effects of ethyl pyruvate through inhibiting high-mobility group box 1 expression and TLR4/NF-κB pathway after traumatic brain injury in the rat. Mediat. Inflamm. 2011, 2011:807142.
174. Tahara K., Kim H.D., Jin J.J., Maxwell J.A., Li L., Fukuchi K. Role of Toll-like receptor signalling in A{beta} uptake and clearance. Brain 2006, 129:3006-3019.
175. Takeda K., Akira S. Toll-like receptors in innate immunity. Int. Immunol. 2005, 17:1-14.
176. Takeuchi O., Akira S. MyD88 as a bottle neck in Toll/IL-1 signaling. Curr. Top. Microbiol. Immunol. 2002, 270:155-167.
177. Takeuchi H., Jin S., Wang J., Zhang G., Kawanokuchi J., Kuno R., Sonobe Y., Mizuno T., Suzumura A. Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J. Biol. Chem. 2006, 281:21362-21368.
178. Tang A.H., Brunn G.J., Cascalho M., Platt J.L. Pivotal advance: endogenous pathway to SIRS, sepsis, and related conditions. J. Leukoc. Biol. 2007, 82:282-285.
179. Tang S.C., Arumugam T.V., Xu X., Cheng A., Mughal M.R., Jo D.G., Lathia J.D., Siler D.A., Chigurupati S., Ouyang X., Magnus T., Camandola S., Mattson M.P. Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:13798-13803.
180. Tansey M.G., Goldberg M.S. Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol. Dis. 2010, 37:510-518.
181. Tarkowski A., Bjersing J., Shestakov A., Bokarewa M.I. Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. J. Cell. Mol. Med. 2009, 14:1419-1431.
182. Triantafilou M., Gamper F.G., Haston R.M., Mouratis M.A., Morath S., Hartung T., Triantafilou K. Membrane sorting of toll like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J. Biol. Chem. 2006, 281:31002-31011.
183. Tufekci K.U., Genc S., Genc K. The endotoxin-induced neuroinflammation model of Parkinson's disease 2011, 2011:487450.
184. Udan M.L., Ajit D., Crouse N.R., Nichols M.R. Toll-like receptors 2 and 4 mediate Abeta (1-42) activation of the innate immune response in a humanmonocytic cell line. J. Neurochem. 2008, 104:524-533.
185. Urcelay E., Blanco-Kelly F., de Las Heras V., de la Concha E.G., Arroyo R., Martínez A. TLR4 haplotypes in multiple sclerosis: a case-control study in the Spanish population. J. Neuroimmunol. 2007, 192:215-218.
186. Vabulas R.M., Ahmad-Nejad P., Ghose S., Kirschning C.J., Issels R.D., Wagner H. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J. Biol. Chem. 2002, 277:15107-15112.
187. Vabulas R.M., Braedel S., Hilf N., Singh-Jasuja H., Herter S., Ahmad-Nejad P., Kirschning C.J., Da Costa C., Rammensee H.G., Wagner H., Schild H. The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the toll-like receptor 2/4 pathway. J. Biol. Chem. 2002, 277:20847-20853.
188. van de Veerdonk F.L., Teirlinck A.C., Kleinnijenhuis J., Kullberg B.J., van Crevel R., van der Meer J.W., Joosten L.A., Netea M.G. Mycobacterium tuberculosis induces IL-17A responses through TLR4 and dectin-1 and is critically dependent on endogenous IL-1. J. Leukoc. Biol. 2010, 88:227-232.
189. Vogl T., Tenbrock K., Ludwig S., Leukert N., Ehrhardt C., van Zoelen M.A., Nacken W., Foell D., van der Poll T., Sorg C., Roth J. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat. Med. 2007, 13:1042-1049.
190. Volz H.C., Kaya Z., Katus H.A., Andrassy M. The role of HMGB1/RAGE in inflammatory cardiomyopathy. Semin. Thromb. Hemost. 2010, 36:185-194.
191. Wadachi R., Hargreaves K.M. Trigeminal nociceptors express TLR-4 and CD14: a mechanism for pain due to infection. J. Dent. Res. 2006, 85:49-53.
192. Waldner H. The role of innate immune responses in autoimmune disease development. Autoimmun. Rev. 2009, 8:400-404.
193. Walter S., Letiembre M., Liu Y., Heine H., Penke B., Hao W., Bode B., Manietta N., Walter J., Schulz-Schuffer W., Fassbender K. Role of the Toll-like receptor 4 in neuroinflammation in Alzheimer's disease. Cell. Physiol. Biochem. 2007, 20:947-956.
194. Wang J., Campbell I.L. Cytokine signaling in the brain: putting a SOCS in it?. J. Neurosci. Res. 2002, 67:423-427.
195. Wang X., Jung J., Asahi M., Chwang W., Russo L., Moskowitz M.A., Dixon C.E., Fini M.E., Lo E.H. Effects of matrix metalloproteinase-9 gene knock-out on morphological and motor outcomes after traumatic brain injury. J. Neurosci. 2000, 20:7037-7042.
196. Wang J.Y., Wen L.L., Huang Y.N., Chen Y.T., Ku M.C. Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidative stress and indirect protection via suppression of glia-mediated inflammation. Curr. Pharm. Des. 2006, 12:3521-3533.
197. Wu F.X., Bian J.J., Miao X.R., Huang S.D., Xu X.W., Gong D.J., Sun Y.M., Lu Z.J., Yu W.F. Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain. Int. J. Med. Sci. 2010, 7:251-259.
198. Xie Z., Wei M., Morgan T.E., Fabrizio P., Han D., Finch C.E., Longo V.D. Peroxynitrite mediates neurotoxicity of amyloid beta-peptide 1-42- and lipopolysaccharide-activated microglia. J. Neurosci. 2002, 22:3484-3492.
199. Xilouri M., Vogiatzi T., Vekrellis K., Park D., Stefanis L. Abberant alpha-synuclein confers toxicity to neurons in part through inhibition of chaperone-mediated autophagy. PLoS One 2009, 4:e5515.
200. Yamamoto M., Sato S., Hemmi H., Hoshino K., Kaisho T., Sanjo H., Takeuchi O., Sugiyama M., Okabe M., Takeda K., Akira S. Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway. Science 2003, 301:640-643.
201. Yamamoto M., Sato S., Hemmi H., Uematsu S., Hoshino K., Kaisho T., Takeuchi O., Takeda K., Akira S. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat. Immunol. 2003, 4:1144-1150.
202. Yamazaki T., Yang X.O., Chung Y., Fukunaga A., Nurieva R., Pappu B., Martin-Orozco N., Kang H.S., Ma L., Panopoulos A.D., Craig S., Watowich S.S., Jetten A.M., Tian Q., Dong C. CCR6 regulates the migration of inflammatory and regulatory T cells. J. Immunol. 2008, 181:8391-8401.
203. Yanai H., Ban T., Wang Z., Choi M.K., Kawamura T., Negishi H., Nakasato M., Lu Y., Hangai S., Koshiba R., Savitsky D., Ronfani L., Akira S., Bianchi M.E., Honda K., Tamura T., Kodama T., Taniguchi T. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 2009, 462:99-103.
204. Yang R.B., Mark M.R., Gurney A.L., Godowski P.J. Signaling events induced by lipopolysaccharide-activated Toll-like receptor 2. J. Immunol. 1999, 163:639-643.
205. Yang X.O., Chang S.H., Park H., Nurieva R., Shah B., Acero L., Wang Y.H., Schluns K.S., Broaddus R.R., Zhu Z., Dong C. Regulation of inflammatory responses by IL-17F. J. Exp. Med. 2008, 205:1063-1075.
206. Yang Q.W., Xiang J., Zhou Y., Zhong Q., Li J.C. Targeting HMGB1/TLR4 signaling as a novel approach to treatment of cerebral ischemia. Front. Biosci. 2010, 2:1081-1091.
207. Yao S., Pandey P., Ljunggren-Rose A., Sriram S. LPS mediated injury to oligodendrocytes is mediated by the activation of nNOS: relevance to human demyelinating disease. Nitric Oxide 2010, 22:109-204.
208. Yao S.Y., Ljunggren-Rose A., Chandramohan N., Whetsell W.O., Sriram S. In vitro and in vivo induction and activation of nNOS by LPS in oligodendrocytes. J. Neuroimmunol. 2010, 229:146-156.
209. Yao S.Y., Natarajan C., Sriram S. nNOS mediated mitochondrial injury in LPS stimulated oligodendrocytes. Mitochondrion 2012, 12:336-344.
210. Yasuda T., Nakata Y., Choong C.J., Mochizuki H. Neurodegenerative changes initiated by presynaptic dysfunction. Transl. Neurodegener. 2013, 2:16.
211. 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, 19:533-542.
212. Zhang Q., Raoof M., Chen Y., Sumi Y., Sursal T., Junger W., Brohi K., Itagaki K., Hauser C.J. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 2010, 464:104-107.
213. Zhang R., Hadlock K.G., Do H., Yu S., Honrada R., Champion S., Forshew D., Madison C., Katz J., Miller R.G., McGrath M.S. Gene expression profiling in peripheral blood mononuclear cells from patients with sporadic amyotrophic lateral sclerosis (sALS). J. Neuroimmunol. 2011, 230:114-123.
214. Zhang Z., Zhang Z.Y., Wu Y., Schluesener H.J. Immunolocalization of Toll-like receptors 2 and 4 as well as their endogenous ligand, heat shock protein 70, in rat traumatic brain injury. Neuroimmunomodulation 2012, 19:10-19.
215. Zhao W., Beers D.R., Henkel J.S., Zhang W., Urushitani M., Julien J.P., Appel S.H. Extracellular mutant SOD1 induces microglial-mediated motoneuron injury. Glia 2010, 58:231-243.
216. Ziegler G., Freyer D., Harhausen D., Khojasteh U., Nietfeld W., Trendelenburg G. Blocking TLR2 in vivo protects against accumulation of inflammatory cells and neuronal injury in experimental stroke. J. Cereb. Blood Flow Metab. 2011, 31:757-766.