Potential drugs targeting microglia: Current knowledge and future prospects

CNS and Neurological Disorders - Drug Targets

Volumn 12, Issue 6, 2013, Pages 799-806

  Rangarajan, Parakalan ^a   Eng Ang, Ling ^a   Dheen, S Thameem ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

Brain injury; Epigenetics; Glucocorticoids; Inflammation; Microglia; Minocycline; miRNA; Neurodegeneration; Retinoic acid

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; CD4 ANTIGEN; CHEMOKINE RECEPTOR CCR3; CHEMOKINE RECEPTOR CCR5; COPPER ZINC SUPEROXIDE DISMUTASE; MICRORNA 155; MICRORNA 34A; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N, N DIMETHYLSPHINGOSINE; RETINOIC ACID; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

AGING; AMYOTROPHIC LATERAL SCLEROSIS; APOPTOSIS; AUTOIMMUNE DISEASE; BRAIN INJURY; CENTRAL NERVOUS SYSTEM INFECTION; CEREBROVASCULAR DISEASE; DEVELOPMENTAL DISORDER; DNA METHYLATION; DOWN REGULATION; DRUG DELIVERY SYSTEM; DRUG TARGETING; GENE EXPRESSION; HUMAN; IMMUNE RESPONSE; MICROGLIA; PHAGOCYTOSIS; PROTEIN EXPRESSION; REVIEW; UPREGULATION;

ANIMALS; DRUG DELIVERY SYSTEMS; FORECASTING; HUMANS; INFLAMMATION; MICROGLIA; NERVOUS SYSTEM DISEASES; PLANT PREPARATIONS; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION; TRETINOIN;

EID: 84888074955     PISSN: 18715273     EISSN: 19963181     Source Type: Journal    
DOI: 10.2174/18715273113126660175     Document Type: Review

References (90)

1. Stence, N.; Waite, M.; Dailey, M.E. Dynamics of microglial activation: A confocal time-lapse analysis in hippocampal slices. Glia, 2001, 33(3), 256-266.
2. Orłowski, D.; Sołtys, Z.; Janeczko, K. Morphological development of microglia in the postnatal rat brain: A quantitative study. Intl. J. Develop. Neurosci., 2003, 21(8), 445-450.
3. 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.
4. Innocenti, G.M.; Clarke, S.; Koppel, H. Transitory macrophages in the white matter of the developing visual cortex. II. Development and relations with axonal pathways. Develop. Brain Res., 1983, 11(1), 55-66.
5. Mallat, M.; Marín-Teva, J.L.; Chéret, C. Phagocytosis in the developing CNS: more than clearing the corpses. Curr. Opin. Neurobiol., 2005, 15(1), 101-107.
6. Nimmerjahn, A.; Kirchhoff, F.; Helmchen, F. Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo. Science, 2005, 308(5726), 1314-1318.
7. Ling, E.A.; Ng, Y.K.; Wu, C.H.; Kaur, C. Microglia: its development and role as a neuropathology sensor. In: Progress in Brain Research. Castellano B.; Lopez, M.N.-S., Eds.; Elsevier, 2001; Vol. 132, pp. 61-79.
8. Kreutzberg, G.W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci., 1996, 19(8), 312-318.
9. Streit, W.J. Microglial senescence: does the brain's immune system have an expiration date? Trends Neurosci., 2006, 29(9), 506-510.
10. Luo, X.-G.; Ding, J.-Q.; Chen, S.-D. Microglia in the aging brain: relevance to neurodegeneration. BioMed Central, 2010.
11. Lucin, K.M.; Wyss-Coray, T. Immune Activation in Brain Aging and Neurodegeneration: Too Much or Too Little? Neuron, 2009, 64(1), 110-122.
12. Qin, L.; Liu, Y.; Cooper, C.; Liu, B.; Wilson, B.; Hong, J.-S. Microglia enhance β-amyloid peptide-induced toxicity in cortical and mesencephalic neurons by producing reactive oxygen species. J. Neurochem., 2002, 83(4), 973-983.
13. Dheen, S.T.; Jun, Y.; Yan, Z.; Tay, S.S.W.; Ang Ling, E. Retinoic acid inhibits expression of TNF-α and iNOS in activated rat microglia. Glia, 2005, 50(1), 21-31.
14. 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 α-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB J., 2005, 19(6), 533-542.
15. Park, E.; Bell, J.D.; Baker, A.J. Traumatic brain injury: Can the consequences be stopped? Can. Med. Assoc. J., 2008, 178(9), 1163-1170.
16. Werner, C.; Engelhard, K. Pathophysiology of traumatic brain injury. Br. J. Anaesthes., 2007, 99(1), 4-9.
17. Ramlackhansingh, A.F.; Brooks, D.J.; Greenwood, R.J.; Bose, S.K.; Turkheimer, F.E.; Kinnunen, K.M.; Gentleman, S.; Heckemann, R.A.; Gunanayagam, K.; Gelosa, G.; Sharp, D.J. Inflammation after trauma: Microglial activation and traumatic brain injury. Ann. Neurol., 2011, 70(3), 374-383.
18. Nagamoto-Combs, K.; McNeal, D.W.; Morecraft, R.J.; Combs, C.K. Prolonged Microgliosis in the Rhesus Monkey Central Nervous System after Traumatic Brain Injury. J. Neurotrauma, 2007, 24(11), 1719-1742.
19. Dohi, K.; Ohtaki, H.; Nakamachi, T.; Yofu, S.; Satoh, K.; Miyamoto, K.; Song, D.; Tsunawaki, S.; Shioda, S.; Aruga, T. Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury. J. Neuroinflammation, 2010, 7(1), 41.
20. Wood, P. Microglia as a unique cellular target in the treatment of stroke: potential neurotoxic mediators produced by activated microglia. Neurol. Res., 1995, 17(4), 242-248.
21. Kaushal, V.; Schlichter, L.C. Mechanisms of Microglia-Mediated Neurotoxicity in a New Model of the Stroke Penumbra. J. Neurosci., 2008, 28(9), 2221-2230.
22. Thored, P.; Heldmann, U.; Gomes-Leal, W.; Gisler, R.; Darsalia, V.; Taneera, J.; Nygren, J.M.; Jacobsen, S.-E.W.; Ekdahl, C.T.; Kokaia, Z.; Lindvall, O. Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia, 2009, 57(8), 835-849.
23. Volpe, J.J. Neurobiology of Periventricular Leukomalacia in the Premature Infant. Pediatr. Res., 2001, 50(5), 553-562.
24. Baud, O.; Daire, J.-L.; Dalmaz, Y.; Fontaine, R.H.; Krueger, R.C.; Sebag, G.; Evrard, P.; Gressens, P.; Verney, C. Gestational Hypoxia Induces White Matter Damage in Neonatal Rats: A New Model of Periventricular Leukomalacia. Brain Pathol., 2004, 14(1), 1-10.
25. Deng, Y.; Lu, J.; Sivakumar, V.; Ling, E.A.; Kaur, C. Amoeboid Microglia in the Periventricular White Matter Induce Oligodendrocyte Damage through Expression of Proinflammatory Cytokines via MAP Kinase Signaling Pathway in Hypoxic Neonatal Rats. Brain Pathol., 2008, 18(3), 387-400.
26. Murugan, M.; Sivakumar, V.; Lu, J.; Ling, E.-A.; Kaur, C. Expression of N-methyl D-aspartate receptor subunits in amoeboid microglia mediates production of nitric oxide via NF-κB signaling pathway and oligodendrocyte cell death in hypoxic postnatal rats. Glia, 2011, 59(4), 521-539.
27. Rathnasamy, G.; Ling, E.-A.; Kaur, C. Iron and Iron Regulatory Proteins in Amoeboid Microglial Cells Are Linked to Oligodendrocyte Death in Hypoxic Neonatal Rat Periventricular White Matter through Production of Proinflammatory Cytokines and Reactive Oxygen/Nitrogen Species. J. Neurosci., 2011, 31(49), 17982-17995.
28. Nau, R.; Brück, W. Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci., 2002, 25(1), 38-45.
29. Koedel, U.; Pfister, H.-W. Oxidative Stress in Bacterial Meningitis. Brain Pathol., 1999, 9(1), 57-67.
30. Rock, R.B.; Gekker, G.; Hu, S.; Sheng, W.S.; Cheeran, M.; Lokensgard, J.R.; Peterson, P.K. Role of Microglia in Central Nervous System Infections. Clin. Microbiol. Rev., 2004, 17(4), 942-964.
31. 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. The Journal of Neuroscience. J. Neurosci., 2002, 22(7), 2478-2486.
32. Ribes, S.; Ebert, S.; Regen, T.; Agarwal, A.; Tauber, S.C.; Czesnik, D.; Spreer, A.; Bunkowski, S.; Eiffert, H.; Hanisch, U.-K.; Hammerschmidt, S.; Nau, R. Toll-Like Receptor Stimulation Enhances Phagocytosis and Intracellular Killing of Nonencapsulated and Encapsulated Streptococcus pneumoniae by Murine Microglia. Infect. Immun., 2010, 78(2), 865-871.
33. Lehnardt, S.; Wennekamp, J.; Freyer, D.; Liedtke, C.; Krueger, C.; Nitsch, R.; Bechmann, I.; Weber, J.R.; Henneke, P. TLR2 and Caspase-8 Are Essential for Group B Streptococcus-Induced Apoptosis in Microglia. J. Immunol., 2007, 179(9), 6134-6143.
34. Price, R.; Brew, B.; Sidtis, J.; Rosenblum, M.; Scheck, A.; Cleary, P. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science, 1988, 239(4840), 586-592.
35. Persidsky, Y.; Gendelman, H.E. Mononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection. J. Leukocyte Biol., 2003, 74(5), 691-701.
36. He, J.; Chen, Y.; Farzan, M.; Choe, H.; Ohagen, A.; Gartner, S.; Busciglio, J.; Yang, X.; Hofmann, W.; Newman, W.; Mackay, C.R.; Sodroski, J.; Gabuzda, D. CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature, 1997, 385(6617), 645-649.
37. Minagar, A.; Shapshak, P.; Fujimura, R.; Ownby, R.; Heyes, M.; Eisdorfer, C. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J. Neurol. Sci., 2002, 202(1-2), 13-23.
38. Vallat-Decouvelaere, A.V.; Chretien, F.; Gras, G.; Le Pavec, G.; Dormont, D.; Gray, F. Expression of Excitatory Amino Acid Transporter-1 in Brain Macrophages and Microglia of HIVInfected Patients. A Neuroprotective Role for Activated Microglia? J. Neuropathol. Exp. Neurol., 2003, 62(5), 475-485.
39. 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.
40. Sapp, E.; Kegel, K.B.; Aronin, N.; Hashikawa, T.; Uchiyama, Y.; Tohyama, K.; Bhide, P.G.; Vonsattel, J.P.; Difiglia, M. Early and Progressive Accumulation of Reactive Microglia in the Huntington Disease Brain. J. Neuropathol. Exp. Neurol., 2001, 60(2), 161-172.
41. 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(5778), 1389-1392.
42. Boillée, S.; Cleveland, D.W. Revisiting oxidative damage in ALS: microglia, Nox, and mutant SOD1. J Clin. Invest., 2008, 118(2), 474-478.
43. Li, H.; Cuzner, M.L.; Newcombe, J. Microglia-derived macrophages in early multiple sclerosis plaques. Neuropathology and Applied Neurobiology. Neuropathol. Appl. Neurobiol., 1996, 22(3), 207-215.
44. Trapp, B.D.; Bö, L.; Mörk, S.; Chang, A. Pathogenesis of tissue injury in MS lesions. J. Neuroimmunol., 1999, 98(1), 49-56.
45. Li, J.; Baud, O.; Vartanian, T.; Volpe, J.J.; Rosenberg, P.A. Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes. Proc. Natl. Acad. Sci. USA, 2005, 102(28), 9936-9941.
46. Drager, U.C. Sci. Retinoic Acid Signaling in the Functioning Brain. Sci STKE. STKE, 2006, 2006(324), pe10.
47. Maden, M. Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat. Rev. Neurosci., 2007, 8(10), 755-765.
48. Lane, M.A.; Bailey, S.J. Role of retinoid signalling in the adult brain. Prog. Neurobiol., 2005, 75(4), 275-293.
49. Enderlin, V.; Pallet, V.; Alfos, S.; Dargelos, E.; Jaffard, R.; Garcin, H.; Higueret, P. Age-related decreases in mRNA for brain nuclear receptors and target genes are reversed by retinoic acid treatment. Neurosci. Lett., 1997, 229(2), 125-129.
50. Ding, Y.; Qiao, A.; Wang, Z.; Goodwin, J.S.; Lee, E.-S.; Block, M.L.; Allsbrook, M.; McDonald, M.P.; Fan, G.-H. Retinoic Acid Attenuates β-Amyloid Deposition and Rescues Memory Deficits in an Alzheimer's Disease Transgenic Mouse Model. J. Neurosci., 2008, 28(45), 11622-11634.
51. Xu, J.; Drew, P.D. 9-Cis-retinoic acid suppresses inflammatory responses of microglia and astrocytes. J. Neuroimmunol., 2006, 171(1), 135-144.
52. Levin, A.A.; Sturzenbecker, L.J.; Kazmer, S.; Bosakowski, T.; Huselton, C.; Allenby, G.; Speck, J.; Ratzeisen, C.; Rosenberger, M.; Lovey, A.; Grippo, J.F. 9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR[alpha]. Nature, 1992, 355(6358), 359-361.
53. Xu, J.; Storer, P.D.; Chavis, J.A.; Racke, M.K.; Drew, P.D. Agonists for the peroxisome proliferator-activated receptor-α and the retinoid X receptor inhibit inflammatory responses of microglia. J. Neurosci. Res., 2005, 81(3), 403-411.
54. Diab, A.; Hussain, R.Z.; Lovett-Racke, A.E.; Chavis, J.A.; Drew, P.D.; Racke, M.K. Ligands for the peroxisome proliferatoractivated receptor-γ and the retinoid X receptor exert additive antiinflammatory effects on experimental autoimmune encephalomyelitis. J. Neuroimmunol., 2004, 148(1), 116-126.
55. Nissen, R.M.; Yamamoto, K.R. The glucocorticoid receptor inhibits NFκB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Develop., 2000, 14(18), 2314-2329.
56. Bladh, L.-G.; Lidén, J.; Dahlman-Wright, K.; Reimers, M.; Nilsson, S.; Okret, S. Identification of Endogenous Glucocorticoid Repressed Genes Differentially Regulated by a Glucocorticoid Receptor Mutant Able to Separate between Nuclear Factor-κB and Activator Protein-1 Repression. Molecular Pharmacology. Mol. Pharmacol., 2005, 67(3), 815-826.
57. Kassel, O.; Sancono, A.; Kratzschmar, J.; Kreft, B.; Stassen, M.; Cato, A.C.B. Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1. EMBO J., 2001, 20(24), 7108-7116.
58. Wang, X.; Nelin, L.D.; Kuhlman, J.R.; Meng, X.; Welty, S.E.; Liu, Y. The role of MAP kinase phosphatase-1 in the protective mechanism of dexamethasone against endotoxemia. Life Sci., 2008, 83(19-20), 671-680.
59. Kaur, C.; Wu, C.H.; Wen, C.Y.; Ling, E.A. The effects of subcutaneous injections of glucocorticoids on amoeboid microglia in postnatal rats. Arch. Histol. Cytol., 1994, 57(5), 449-459.
60. Zhou, Y.; Ling, E.-A.; Dheen, S.T. Dexamethasone suppresses monocyte chemoattractant protein-1 production via mitogen activated protein kinase phosphatase-1 dependent inhibition of Jun N-terminal kinase and p38 mitogen-activated protein kinase in activated rat microglia. J. Neurochem., 2007, 102(3), 667-678.
61. Huo, Y.; Rangarajan, P.; Ling, E.-A.; Dheen, S.T. Dexamethasone inhibits the Nox-dependent ROS production via suppression of MKP-1-dependent MAPK pathways in activated microglia. BMC Neurosci., 2011, 12(1), 49.
62. Lieb, K.; Engels, S.; Fiebich, B.L. Inhibition of LPS-induced iNOS and NO synthesis in primary rat microglial cells. Neurochem. Intl., 2003, 42(2), 131-137.
63. Brooke, S.M.; Sapolsky, R.M. Glucocorticoid Exacerbation of gp120 Neurotoxicity: Role of Microglia. Exp. Neurol., 2002, 177(1), 151-158.
64. Nair, A.; Bonneau, R.H. Stress-induced elevation of glucocorticoids increases microglia proliferation through NMDA receptor activation. J. Neuroimmunol., 2006, 171(1-2), 72-85.
65. Ros-Bernal, F.; Hunot, S.; Herrero, M.T.; Parnadeau, S.; Corvol, J.-C.; Lu, L.; Alvarez-Fischer, D.; Carrillo-de Sauvage, M.A.; Saurini, F.; Coussieu, C.; Kinugawa, K.; Prigent, A.; Höglinger, G.; Hamon, M.; Tronche, F.; Hirsch, E.C.; Vyas, S. Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in parkinsonism. Proc. Natl. Acad. Sci., 2011, 108(16), 6632-6637.
66. Tikka, T.M.; Koistinaho, J.E. Minocycline Provides Neuroprotection Against N-Methyl-d-aspartate Neurotoxicity by Inhibiting Microglia. J. Immunol., 2001, 166(12), 7527-7533.
67. Schildknecht, S.; Pape, R.; Müller, N.; Robotta, M.; Marquardt, A.; Bürkle, A.; Drescher, M.; Leist, M. Neuroprotection by Minocycline Caused by Direct and Specific Scavenging of Peroxynitrite. J. Biol. Chem., 2011, 286(7), 4991-5002.
68. Keller, A.F.; Gravel, M.; Kriz, J. Treatment with minocycline after disease onset alters astrocyte reactivity and increases microgliosis in SOD1 mutant mice. Exp. Neurol., 2011, 228(1), 69-79.
69. Sriram, K.; Miller, D.B.; O'Callaghan, J.P. Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-α. J. Neurochem., 2006, 96(3), 706-718.
70. Taha, T.; Hannun, Y.; Obeid, L. Sphingosine kinase: biochemical and cellular regulation and role in disease. J. Biochem. Mol. Biol., 2006, 39(2), 113-131.
71. Nayak, D.; Huo, Y.; Kwang, W.X.T.; Pushparaj, P.N.; Kumar, S.D.; Ling, E.A.; Dheen, S.T. Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia. Neuroscience, 2010, 166(1), 132-144.
72. Lin, H.; Baby, N.; Lu, J.; Kaur, C.; Zhang, C.; Xu, J.; Ling, E.-A.; Dheen, S.T. Expression of sphingosine kinase 1 in amoeboid microglial cells in the corpus callosum of postnatal rats. J. Neuroinflammation, 2011, 8(1), 13.
73. Rayan, N.; Baby, N.; Pitchai, D.; Indraswari, F.; Ling, E.; Lu, J.; Dheen, T. Costunolide inhibits proinflammatory cytokines and iNOS in activated murine BV2 microglia. Front. Biosci., 2011, 3, 1079-1091.
74. Kim, H.Y.; Park, E.J.; Joe, E.-H.; Jou, I. Curcumin Suppresses Janus Kinase-STAT Inflammatory Signaling through Activation of Src Homology 2 Domain-Containing Tyrosine Phosphatase 2 in Brain Microglia. J. Immunol., 2003, 171(11), 6072-6079.
75. Zhang, F.; Liu, J.; Shi, J.-S. Anti-inflammatory activities of resveratrol in the brain: Role of resveratrol in microglial activation. Eur. J. Pharmacol., 2010, 636(1-3), 1-7.
76. Zong, Y.; Ai, Q.-L.; Zhong, L.-M.; Dai, J.-N.; Yang, P.; He, Y.; Sun, J.; Ling, E.-A.; Lu, D. Ginsenoside Rg1 Attenuates Lipopolysaccharide-Induced Inflammatory Responses Via the Phospholipase C-γ1 Signaling Pathway in Murine BV-2 Microglial Cells. Curr. Med. Chem., 2012, 19(5), 770-779.
77. Giorgini, F.; Möller, T.; Kwan, W.; Zwilling, D.; Wacker, J.L.; Hong, S.; Tsai, L.-C.L.; Cheah, C.S.; Schwarcz, R.; Guidetti, P.; Muchowski, P.J. Histone Deacetylase Inhibition Modulates Kynurenine Pathway Activation in Yeast, Microglia, and Mice Expressing a Mutant Huntingtin Fragment. J. Biol. Chem., 2008, 283(12), 7390-7400.
78. Zhang, B.; West, E.J.; Van, K.C.; Gurkoff, G.G.; Zhou, J.; Zhang, X.-M.; Kozikowski, A.P.; Lyeth, B.G. HDAC inhibitor increases histone H3 acetylation and reduces microglia inflammatory response following traumatic brain injury in rats. Brain Res., 2008, 1226(0), 181-191.
79. Chen, P.S.; Wang, C.C.; Bortner, C.D.; Peng, G.S.; Wu, X.; Pang, H.; Lu, R.B.; Gean, P.W.; Chuang, D.M.; Hong, J.S. Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity. Neuroscience, 2007, 149(1), 203-212.
80. Sen, C.K. MicroRNAs as new maestro conducting the expanding symphony orchestra of regenerative and reparative medicine. Physiol. Genom., 2011, 43(10), 517-520.
81. Jaiswal, S.; Chao, M.P.; Majeti, R.; Weissman, I.L. Macrophages as mediators of tumor immunosurveillance. Trends Immunol., 2010, 31(6), 212-219.
82. Junker, A.; Krumbholz, M.; Eisele, S.; Mohan, H.; Augstein, F.; Bittner, R.; Lassmann, H.; Wekerle, H.; Hohlfeld, R.; Meinl, E. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain, 2009, 132(12), 3342-3352.
83. Cardoso, A.L.; Guedes, J.R.; Pereira de Almeida, L.; Pedroso de Lima, M.C. miR-155 modulates microglia-mediated immune response by down-regulating SOCS-1 and promoting cytokine and nitric oxide production. Immunology, 2012, 135(1), 73-88.
84. Saba, R.; Gushue, S.; Huzarewich, R.L.C.H.; Manguiat, K.; Medina, S.; Robertson, C.; Booth, S.A. MicroRNA 146a (miR-146a) Is Over-Expressed during Prion Disease and Modulates the Innate Immune Response and the Microglial Activation State. PLoS ONE, 2012, 7(2), e30832.
85. 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., 2011, 17(1), 64-70.
86. Lockman, P.R.; Mumper, R.J.; Khan, M.A.; Allen, D.D. Nanoparticle Technology for Drug Delivery Across the Blood-Brain Barrier. Drug Develop. Indust. Pharm., 2002, 28(1), 1-13.
87. Brigger, I.; Dubernet, C.; Couvreur, P. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Deliv. Rev., 2002, 54(5), 631-651.
88. Choi, J.; Zheng, Q.; Katz, H.E.; Guilarte, T.R. Silica-Based Nanoparticle Uptake and Cellular Response by Primary Microglia. Environ. Health Perspect., 2009, 118(5).
89. Hutter, E.; Boridy, S.; Labrecque, S.; Lalancette-Hébert, M.; Kriz, J.; Winnik, F.O.M.; Maysinger, D. Microglial Response to Gold Nanoparticles. ACS Nano, 2010, 4(5), 2595-2606.
90. Cucchiarini, M.; Ren, X.L.; Perides, G.; Terwilliger, E.F. Selective gene expression in brain microglia mediated via adeno-associated virus type 2 and type 5 vectors. Gene Ther., 2003, 10(8), 657-667.