Ion channels on Microglia: Therapeutic targets for neuroprotection

CNS and Neurological Disorders - Drug Targets

Volumn 10, Issue 1, 2011, Pages 44-56

  Skaper, Stephen D ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

Alzheimer's disease; Amyloid; ATP; Chloride channels; Microglia; Neuroinflammation; Neurotoxicity; Potassium channels; Purinergic receptors

Indexed keywords

AMYLOID BETA PROTEIN; APAMIN; BENZENE DERIVATIVE; CALCIUM ACTIVATED POTASSIUM CHANNEL; CHLORIDE CHANNEL; CHLORIDE INTRACELLULAR CHANNEL 1; CYTOKINE; ION CHANNEL; NEUROPROTECTIVE AGENT; POTASSIUM CHANNEL BLOCKING AGENT; PURINERGIC P2X7 RECEPTOR; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; TAMAPIN; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; CLIC1 PROTEIN, RAT;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ASTROCYTE; BRAIN ISCHEMIA; CENTRAL NERVOUS SYSTEM DISEASE; COCULTURE; DEMYELINATION; DISEASE EXACERBATION; EXPERIMENTAL MODEL; HUMAN; MACROPHAGE ACTIVATION; MICROGLIA; MULTIPLE SCLEROSIS; NERVE CELL LESION; NERVE CELL NECROSIS; NEUROPATHOLOGY; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PARKINSON DISEASE; RECEPTOR UPREGULATION; RETINA DISEASE; REVIEW; SPINAL CORD INJURY; STROKE; TRANSGENIC MOUSE; TRAUMATIC BRAIN INJURY; WHITE MATTER INJURY; ANIMAL; DEGENERATIVE DISEASE; METABOLISM; MOLECULARLY TARGETED THERAPY; MOUSE; NERVE CELL; PATHOLOGY; PHYSIOLOGY; RAT;

ANIMALS; CHLORIDE CHANNELS; ION CHANNELS; MICE; MICROGLIA; MOLECULAR TARGETED THERAPY; NEURODEGENERATIVE DISEASES; NEURONS; NEUROPROTECTIVE AGENTS; POTASSIUM CHANNELS, CALCIUM-ACTIVATED; RATS; RECEPTORS, PURINERGIC P2X7;

EID: 79960776760     PISSN: 18715273     EISSN: 19963181     Source Type: Journal    
DOI: 10.2174/187152711794488638     Document Type: Review

References (178)

1. Block, M.L.; Zecca, L.; Hong, J.S. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci., 2007, 8, 57-69.
2. Hanisch, U-K.; Kettenmann, H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci., 2007, 10, 1387-1394.
3. Craft, J.M.; Watterson, D.M.; Van Eldik, L.J. Neuroinflammation: a potential therapeutic target. Expert Opin. Ther. Targets, 2005, 9, 887-900.
4. McGeer, P.L.; Schulzer, M.; McGeer, E.G. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology, 1996, 47, 425-432. 52 CNS & Neurological Disorders-Drug Targets, 2011, Vol. 10, No. 1
5. McGeer, P.L.; McGeer, E.G. Polymorphisms in inflammatory genes and the risk of Alzheimer's disease. Arch. Neurol., 2001, 58, 1790-1792.
6. Akiyama, H.; Barger, S.; Barnum, S.; Bradt, B.; Bauer, J.; Cole, G.M.; Cooper, N.R.; Eikelenboom, P.; Emmerling, M.; Fiebich, B.L.; Finch, C.E.; Frautschy, S.; Griffin, W.S.; Hampel, H.; Hull, M.; Landreth, G.; Lue, L.; Mrak, R.; Mackenzie, I.R.; McGeer, P.L.; O'Banion, M.K.; Pachter, J.; Pasinetti, G.; Plata-Salaman, C.; Rogers, J.; Rydel, R.; Shen, Y.; Streit, W.; Strohmeyer, R.; Tooyoma, I.; Van Muiswinkel, F.L.; Veerhuis, R.; Walker, D.; Webster, S.; Wegrzyniak, B.; Wenk, G.; Wyss-Coray, T. Inflammation and Alzheimer's disease. Neurobiol. Aging, 2003, 21, 383-421.
7. McGeer, P.L.; McGeer, E.G. Inflammation and the degenerative diseases of aging. Ann. NY Acad. Sci., 2004, 1035, 104-116.
8. Langford, D.; Masliah, E. Crosstalk between components of the blood brain barrier and cells in the CNS in microglial activation in AIDS. Brain Pathol., 2001, 11, 306-312.
9. Perry, V.H.; Cunningham, C.; Boche, D. Atypical inflammation in the central nervous system in prion disease. Curr. Opin. Neurol., 2002, 15, 349-354.
10. Teismann, T.; Schulz, J.B. Cellular pathology of Parkinson's disease: astrocytes, microglia and inflammation. Cell Tissue Res., 2004, 318, 149-161.
11. Danton, G.H.; Dietrich, W.D. Inflammatory mechanisms after ischemia and stroke. J. Neuropathol. Exp. Neurol., 2003, 62, 127-136.
12. Keane, R.W.; Davis, A.R.; Dietrich, W.D. Inflammatory and apoptotic signaling after spinal cord injury. J. Neurotrauma, 2006, 23, 335-344.
13. Bramlett, H.M.; Dietrich, W.D. Pathophysiology of cerebral ischemia and brain trauma: similarities and differences. J. Cereb. Blood Flow Metab., 2004, 24, 133-150.
14. Pocock, J.M.; Kettenmann, H. Neurotransmitter receptors on microglia. Trends Neurosci., 2007, 30, 527-535.
15. 7 receptors as a transducer in the co-occurrence of neurological/psychiatric and cardiovascular disorders: a hypothesis. Cardiovasc. Psychiatry Neurol., 2009, 2009, 545263.
16. 7 purinergic receptor: from physiology to neurological disorders. FASEB J., 2009, 24, 337-345.
17. North, R.A. Molecular physiology of P2X receptors. Physiol. Rev., 2002, 82, 1013-1067.
18. Burnstock, G. Introduction: P2 receptors. Curr. Top. Med. Chem., 2004, 4, 793-803.
19. Khakh B.S, North R.A. P2X receptors as cell-surface ATP sensors in health and disease. Nature, 2006, 442, 527-532.
20. North, R.A.; Surprenant, A. Pharmacology of cloned P2X receptors. Annu. Rev. Pharmacol. Toxicol., 2006, 40, 563-580.
21. Steinberg, T.H.; Newman, A.S.; Swanson, J.A.; Silverstein, S.C. ATP4-permeabilizes the plasma membrane of mouse macrophages to fluorescent dyes. J. Biol. Chem., 1987, 262, 8884-8888.
22. 7). Science, 1996, 272, 735-738.
23. Di Virgilio, F.; Chiozzi, P.; Ferrari, D.; Falzoni, S.; Sanz, J.M.; Morelli, A.; Torboli, M.; Bolognesi, G.; Baricordi, O.R. Nucleotide receptors: an emerging family of regulatory molecules in blood cells. Blood, 2001, 97, 587-600.
24. 7 receptor. Neuropharmacology, 1997, 36, 1277-1283.
25. Ferrari, D.; Villalba, M.; Chiozzi, P.; Falzoni, S.; Ricciardi-Castagnoli, P.; Di Virgilio, F. Mouse microglia cells express a plasma membrane pore gated by extracellular ATP. J. Immunol., 1996, 156, 1531-1539.
26. 7 receptor expression in rodent brain. J. Neurosci., 2004, 24, 6307-6314.
27. 7 receptor function and immunoreactivity in neurons. Trends Neurosci., 2006, 29, 257-262.
28. 7 receptor antagonists/interleukin-1 inhibitors. J. Med. Chem., 2007, 50, 5882-5885.
29. 7 antagonists. J. Med. Chem., 2008, 51, 3030-3034.
30. 7 antagonist, dose-dependently reduces neuropathic pain in the rat. J. Pharmacol. Exp.Ther., 2006, 319, 1376-1385.
31. 7 receptors induces CCL3 production in microglial cells through transcription factor NFAT. J. Neurochem., 2009, 108, 115-125.
32. 7 receptor-mediated IL-1b release. J. Neurochem., 2008, 106, 271-280.
33. Dinarello, C.A. Immunological and inflammatory functions of the interleukin-1 family. Annu. Rev. Immunol., 2009, 27, 519-550.
34. Perregaux, D.G.; McNiff, P.; Laliberte, R.; Conklyn, M.; Gabel, C.A. ATP acts as an agonist to promote stimulus-induced secretion of IL-1b and IL-18 in human blood. J. Immunol., 2000, 165, 4615-4623.
35. 7 receptors. J. Biol. Chem., 2001, 276, 125-132.
36. 7 receptor. J. Physiol., 1999, 519, 335-346.
37. Ferrari, D.; Chiozzi, P.; Falzoni, S.; Hanau, S.; Di Virgilio, F. Purinergic modulation of interleukin-1 release from microglial cells stimulated with bacterial endotoxin. J. Exp. Med., 1997, 185, 579-582.
38. 7 receptor channels. J. Neurosci., 2002, 22, 3061-3069.
39. Filippini, A.; Taffs, R.E.; Agui, T.; Sitkovsky, M.V. Ecto-ATPase activity in cytolytic T-lymphocytes. Protection from the cytolytic effects of extracellular ATP. J. Biol. Chem., 1990, 265, 334-340.
40. 7-independent mechanism. J. Immunol., 1999, 163, 558-561.
41. Ferrari, D.; Chiozzi, P.; Falzoni, S.; Dal Susino, M.; Collo, G.; Buell, G.; Di Virgilio, F. ATP-mediated cytotoxicity in microglial cells. Neuropharmacology, 1997, 36, 1295-1301.
42. Beigi, R.; Kobatake, E.; Aizawa, M.; Dubyak, G.R. Detection of local ATP release from activated platelets using cell surface- attached firefly luciferase. Am. J. Physiol., 1999, 276(45), C267-C278.
43. Dubyak, G.R.; el-Moatassim, C. Signal transduction via P2- purinergic receptors for extracellular ATP and other nucleotides. Am. J. Physiol., 1993, 265, C577-C606.
44. Lazarowski, E.R.; Boucher, R.C.; and Harden, T.K. Constitutive release of ATP and evidence for major contribution of ectonucleotide pyrophosphatase and nucleoside diphosphokinase to extracellular nucleotide concentrations. J. Biol. Chem., 2000, 275, 31061-31068.
45. Nieber, K.; Eschke, D.; Brand, E. Brain hypoxia: effects of ATP and adenosine. Prog. Brain Res., 1999, 120, 287-297.
46. Pellegatti, P.; Falzoni, S.; Pinton, P.; Rizzuto, R.; Di Virgilio, F. A novel recombinant plasma membrane-targeted luciferase reveals a Ion Channels on Microglia: Therapeutic Targets for Neuroprotection new pathway for ATP secretion. Mol. Cell. Biol., 2005, 16, 3659-3665.
47. 7 nucleotide receptor expression by pro-and anti-inflammatory stimuli in THP-1 monocytes. J. Leukocyte Biol., 1998, 64, 265-273.
48. 7 receptor expression and function in human astrocytes. Glia, 2005, 49, 245-258.
49. Allan, S.M.; Rothwell, N.J. Cytokines and acute neurodegeneration. Nat. Neurosci., 2001, 2, 734-744.
50. 7 receptors in neurodegeneration. Eur. J. Pharmacol., 2002, 447, 261-269.
51. 7 receptor inhibition improves recovery after spinal cord injury. Nat. Med., 2004, 10, 821-827.
52. 7 receptor alters leukocyte function and attenuates an inflammatory response. J. Immunol., 2002, 168, 6436-6445.
53. 7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain, 2005, 114, 386-396.
54. 7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease. J. Biol. Chem., 2003, 278, 13309-13317.
55. 7 receptors on microglial cells mediate injury to cortical neurons in vitro. Glia, 2006, 54, 234-242.
56. McLarnon, J.G.; Ryu, J.K.; Walker, D.G.; Choi, H.B. Upregulated expression of purinergic P2X(7) receptor in Alzheimer disease and amyloid-b peptide-treated microglia and in peptide-injected rat hippocampus. J. Neuropathol. Exp. Neurol., 2006, 65, 1090-1097.
57. 7 receptor expression. J. Immunol., 2009, 182, 4378-4385.
58. 7 receptor expression after ischemia in the cerebral cortex of rats. J. Neuropathol. Exp. Neurol., 2004, 63, 686-699.
59. 7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol., 2006, 6, 12.
60. D'Ambrosi, N.; Finocchi, P.; Apolloni, S.; Cozzolino, M.; Ferri, A.Padovano, V.; Pietrini, G.; Carri, M.T.; Volanté. The proinflammatory action of P2 receptors is enhanced in SOD1 models for amyotrophic lateral sclerosis. J. Immunol., 2009, 183, 4648-4656.
61. 7 deficiency suppresses development of experimental autoimmune encephalomyelitis. J. Neuroinflammation, 2008, 5, 33.
62. 7 receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1 secretion. FASEB J., 2010, 24(8), 2916-2927.
63. Volanté, C.; Amadio, S.; Cavaliere, F.; D'Ambrosi, N.; Vacca, F.Bernardi, G. Extracellular ATP and neurodegeneration. Curr. Drug Targets CNS Neurol. Disord., 2003, 2, 403-412.
64. Honda, S.; Sasaki, Y.; Ohsawa, K.; Imai, Y.; Nakamura, Y.; Inoue, K.; Kohsaka, S. Extracellular ATP and ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J. Neurosci., 2001, 21, 1975-1982.
65. Verderio, C.; Matteoli, M. ATP mediates calcium signalling between astrocytes and microglial cells: modulation by IFN-g. J. Immunol., 2001, 166, 6383-6391. CNS & Neurological Disorders - Drug Targets, 2011, Vol. 10, No. 1 53
66. Waxman, S.G.; Swadlow, H.A. The conduction properties of axons in central white matter. Prog. Neurobiol., 1977, 8, 297-324.
67. Gould, E.; Beylin, A.; Tanapat, P.; Reeves, A.; Shors, T.J. Learning enhances adult neurogenesis in the hippocampal formation. Nat. Neurosci., 1999, 2, 260-265.
68. Mesulam, M.M. A plasticity-based theory of the pathogenesis of Alzheimer's disease. Ann. NY Acad. Sci., 2000, 924, 42-52.
69. Bartzokis, G.; Beckson, M.; Lu, P.H.; Nuechterlein, K.H.; Edwards, N.; Mintz, J. Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study. Arch. Gen. Psychiatry, 2001, 58, 461-465.
70. Felts, P.A.; Baker, T.A.; Smith, K.J. Conduction in segmentally demyelinated mammalian central axons. J. Neurosci., 1997, 17, 7267-7277.
71. O'Sullivan, M.; Jones, D.K.; Summers, P.E.; Morris, R.G.; Williams, S.C.; Markus, H.S. Evidence for cortical disconnection as a mechanism of age-related cognitive decline. Neurology, 2001, 57, 632-638.
72. Ge, Y.; Grossmann, R.I.; Babb, J.S.; Rabin, M.L.; Mannon, L.J.Kolson, D.L. Age-related total gray matter and white matter changes in normal adult brain. Part II: quantitative magnetization transfer ratio histogram analysis. Am. J. Neuroradiol., 2002, 23, 1334-1341.
73. Tang, Y.; Nyengaard, J.R.; Pakkenberg, B.; Gundersen, H.J. Age- induced white matter changes in the human brain: a stereological investigation. Neurobiol. Aging, 1997, 18, 609-615.
74. Braak, H.; Del Tredici, K.; Schultz, C.; Braak, E. Vulnerability of select neuronal types to Alzheimer's disease. Ann. NY Acad. Sci., 2000, 924, 53-61.
75. Bresnahan, J.C. An electron-microscopic analysis of axonal alterations following blunt contusion of the spinal cord of the rhesus monkey (Macaca mulatta). J. Neurol. Sci., 1978, 37, 59-82.
76. Blight, A.R. Macrophages and inflammatory damage in spinal cord injury. J. Neurotrauma, 1992, 9, S83-S91.
77. Yam, P.S.; Takasago, T.; Dewar, D.; Graham, D.I.; McCulloch, J. Amyloid precursor protein accumulates in white matter at the margin of a focal ischemic lesion. Brain Res., 1997, 760, 150-157.
78. Yam, P.S.; Dewar, D.; McCulloch, J. Axonal injury caused by focal cerebral ischemia in the rat. J. Neurotrauma, 1998, 15, 441-450.
79. Peters, A.; Moss, M.B.; Sethares, C. Effects of aging on myelinated nerve fibers in monkey primary visual cortex. J. Comp. Neurol., 2000, 419, 364-376.
80. Bartzokis, G.; Cummings, J.; Sultzer, D.; Henderson, V.W.; Neuchterlein, K.H.; Mintz, J. White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study. Arch. Neurol., 2003, 60, 393-398.
81. Bartzokis, G. Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease. Neurobiol. Aging, 2004, 25, 5-18.
82. Fields, R.D.; Burnstock, G. Purinergic signaling in neuron-glia interactions. Nat. Rev. Neurosci., 2006, 7, 423-436.
83. James, G.; Butt, A.M. P2Y and P2X purinoceptor mediated Ca2+ signalling in glial cell pathology in the central nervous system. Eur. J. Pharmacol., 2002, 447, 247-260.
84. Agresti, C.; Meomartini, M.E.; Amadio, S.; Ambrosini, E.; Serafini, B.; Franchini, L.; Volanté, C.; Aloisi, F.; Visentin, S. Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development. Glia, 2005, 50, 132-144.
85. 7 receptor mRNA in the rat brain. Brain Res., 2008, 1194, 45-55.
86. 7 receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis. J. Neurosci., 2007, 27, 9525-9533.
87. 7 receptors mediate ischemic damage to oligodendrocytes. Glia, 2010, 58, 730-740.
88. Culbert, A.; Skaper, S.D.; Howlett, D.R.; Evans, N.A.; Facci, L.Soden, P.E.; Seymour, Z.M.; Guillot, F.; Gaestel, M.; Richardson, J.C. MAPK-activated protein kinase 2 deficiency in microglia 54 CNS & Neurological Disorders - Drug Targets, 2011, Vol. 10, No. 1 inhibits pro-inflammatory mediator release and resultant neurotoxicity: relevance to neuroinflammation in a transgenic mouse model of Alzheimer disease. J. Biol. Chem., 2006, 281, 23658-23667.
89. Rosin, C.; Bates, T.E.; Skaper, S.D. Excitatory amino acid induced oligodendrocyte cell death in vitro: receptor-dependent and - independent mechanisms. J. Neurochem., 2004, 90, 1173-1185.
90. Vasilevko, V.; Xu, F.; Previti, M.; Van Nostrand, W.E.; Cribbs, D.H. Experimental investigation of antibody-mediated clearance mechanisms of amyloid-in CNS of Tg-SwDI transgenic mice. J. Neurosci., 2007, 27, 13376-13383.
91. 7 receptor-mediated release of excitatory amino acids from astrocytes. J. Neurosci., 2003, 23, 1320-1328.
92. McDonald, J.W.; Althomsons, S.P.; Hyrc, K.L.; Choi, D; Goldberg, M.P. Oligodendrocytes from forebrain are highly vulnerable to AMPA/kainate receptor-mediated excitotoxicity. Nat. Med., 1998, 4, 291-297.
93. Matute, C.; Domercq, M.; Sánchez-Gómez, M.V. Glutamate- mediated glial injury: mechanisms and clinical importance. Glia, 2006, 53, 212-224.
94. Pitt, D.; Werner, P.; Raine, C.S. Glutamate excitotoxicity in a model of multiple sclerosis. Nat. Med., 2000, 6, 67-70.
95. 7 pore. J. Neurosci., 2009, 29, 3781-3791.
96. 7 receptor. FASEB J., 2010, 24(9), 3393-3404.
97. Davalos, D.; Grutzendler, J.; Yang, G.; Kim, J.V.; Zuo, Y.; Jung, S.; Littman, D.R.; Dustin, M.L.; Gan, W.B. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci., 2005, 8, 752-758.
98. Sorce, S.; Krause, K.H. NOX enzymes in the central nervous system: from signaling to disease. Antioxid. Redox. Signal., 2009, 11, 2481-2504.
99. Floyd, R.A. Antioxidants, oxidative stress, and degenerative neurological disorders. Proc. Soc. Exp. Biol. Med., 1999, 222, 236-245.
100. Sultana, R.; Butterfield, D.A. Role of oxidative stress in the progression of Alzheimer's disease. J. Alzheimers Dis., 2010, 19, 341-353.
101. Reynolds, A.; Laurie, C.; Mosley, R.L.; Gendelman, H.E. Oxidative stress and the pathogenesis of neurodegenerative disorders. Int. Rev. Neurobiol., 2007, 82, 297-325.
102. Ducharme, G.; Newell, E.W.; Pinto, C.; Schlichter, L.C. Small- conductance Cl-channels contribute to volume regulation and phagocytosis in microglia. Eur. J. Neurosci., 2007, 26, 2119-2130.
103. Milton, R.H.; Abeti, R.; Averaimo, S.; DeBiasi, S.; Vitellaro, L.; Jiang, L.; Curmi, P.M.G.; Breit, S.N.; Duchen, M.R.; Mazzanti, M. CLIC1 function is required for -amyloid-induced generation of reactive oxygen species by microglia. J. Neurosci., 2008, 28, 11488-11499.
104. Moreland, J.G.; Davis, A.P.; Bailey, G.; Nauseef, W.M.; Lamb, F.S. Anion channels, including ClC-3, are required for normal neutrophil oxidative function, phagocytosis, and transendothelial migration. J. Biol. Chem., 2006, 281, 12277-12288.
105. Valenzuela, S.M.; Martin, D.K.; Por, S.B.; Robbins, J.M.; Warton, K.; Bootcov, M.R.; Schofield, P.R.; Campbell, T.J.; Breit, S.N. Molecular cloning and expression of a chloride ion channel of cell nuclei. J. Biol. Chem., 1997, 272, 12575-12582.
106. Harrop, S.J.; DeMaere, M.Z.; Fairlie, W.D.; Reztsova, T.; Valenzuela, S.M.; Mazzanti, M.; Tonini, R.; Qiu, M.R.; Jankova, L.; Warton, K.; Bauskin, A.R.; Wu, W.M.; Pankhurst, S.; Campbell, T.J.; Breit, S.N.; Curmi, P.M. Crystal structure of a soluble form of the intracellular chloride ion channel CLIC1 (NCC27) at 1.4-A resolution. J. Biol. Chem., 2001, 276, 44993-45000.
107. Littler, D.R.; Harrop, S.J.; Fairlie, W.D.; Brown, L.J.; Pankhurst, G.J.; Pankhurst, S.; DeMaere, M.Z.; Campbell, T.J.; Bauskin, A.R.; Tonini, R.; Mazzanti, M.; Breit, S.N.; Curmi, P.M.J. The intracellular chloride ion channel protein CLIC1 undergoes a Stephen D. Skaper redox-controlled structural transition. J. Biol. Chem., 2004, 279, 9298-9305.
108. Shimohama, S.; Tanino, H.; Kawakami, N.; Okamura, N.; Kodama, H.; Yamaguchi, T.; Hayakawa, T.; Nunomura, A.; Chiba, S.; Perry, G.; Smith, M.; Fujimoto, S. Activation of NADPH oxidase in Alzheimer's disease brains. Biochem. Biophys. Res. Commun., 2000, 273, 5-9.
109. Parachikova, A.; Agadjanyan, M.G.; Cribbs, D.H.; Blurton-Jones, M.; Perreau, V.; Rogers, J.; Beach, T.G.; Cotman, C.W. Inflammatory changes parallel the early stages of Alzheimer disease. Neurobiol. Aging, 2007, 28, 1821-1833.
110. Bianca, V.D.; Dusi, S.; Bianchini, E.; Dal Prà, I.; Rossi, F.-Amyloid activates the O2 forming NADPH oxidase in microglia, monocytes, and neutrophils: a possible inflammatory mechanism of neuronal damage in Alzheimer's disease. J. Biol. Chem., 1999, 274, 15493-15499.
111. Novarino, G.; Fabrizi, C.; Tonini, R.; Denti, M.A.; Malchiodi-Albedi, F.; Lauro, G.M.; Sacchetti, B.; Paradisi, S.; Ferroni, A.; Curmi, P.M.; Breit, S.N.; Mazzanti, M. Involvement of the intracellular ion channel CLIC1 in microglia-mediated -amyloid-induced neurotoxicity. J. Neurosci., 2004, 24, 5322-5330.
112. Paradisi, S.; Matteucci, A.; Fabrizi, C.; Denti, M.A.; Abeti, R.Breit, S.N.; Malchiodi-Albedi, F.; Mazzanti, M. Blockade of chloride intracellular ion channel 1 stimulates A phagocytosis. J. Neurosci. Res., 2008, 86, 2488-2498.
113. Tonini, R.; Ferroni, A.; Valenzuela, S.M.; Warton, K.; Campbell, T.J.; Breit, S.N.; Mazzanti, M. Functional characterization of the NCC27 nuclear protein in stable transfected cho-k1 cells. FASEB J., 2000, 14, 1171-1178.
114. Valenzuela, S.M.; Mazzanti, M.; Tonini, R.; Qiu, M.R.; Warton, K.; Musgrove, E.A.; Campbell, T.J.; Breit, S.N. The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle. J. Physiol., 2000, 529, 541-552.
115. Inoue, K.; Nakajima, K.; Morimoto, T.; Kikuchi, Y.; Koizumi, S.Illes, P.; Kohsaka, S. ATP stimulation of Ca2+-dependent plasminogen release from cultured microglia. Br. J. Pharmacol., 1998, 123, 1304-1310.
116. Moller, T.; Contos, J.J.; Musante, D.B.; Chun, J.; Ransom, B.R. Expression and function of lysophosphatidic acid receptors in cultured rodent microglial cells. J. Biol. Chem., 2001, 276, 25946-25952.
117. D'Aversa, T.G.; Yu, K.O.; Berman, J.W. Expression of chemokines by human fetal microglia after treatment with the human immunodeficiency virus type 1 protein Tat. J. Neurovirol., 2004, 10, 86-97.
118. Farber, K.; Kettenmann, H. Functional role of calcium signals for microglial function. Glia, 2006, 54, 656-665.
119. Kohler, M.; Hirschberg, B.; Bond, C.T.; Kinzie, J.M.; Marrion, N.V.; Maylie, J.; Adelman, J.P. Small-conductance, calcium- activated potassium channels from mammalian brain. Science, 1996, 273, 1709-1714.
120. Xia, X.M.; Fakler, B.; Rivard, A.; Wayman, G.; Johnson-Pais, T.Keen, J.E.; Ishii, T.; Hirschberg, B.; Bond, C.T.; Lutsenko, S.Maylie, J.; Adelman, J.P. Mechanism of calcium gating in small- conductance calcium-activated potassium channels. Nature, 1998, 395, 503-507.
121. Stocker, M. Ca2+-activated K channels: molecular determinants and function of the SK family. Nat. Rev. Neurosci., 2004, 5, 758-770.
122. Jensen, B.S.; Hertz, M.; Christophersen, P.; Madsen, L.S. The Ca2+-activated K+ channel of intermediate conductance: a possible target for immune suppression. Expert Opin. Ther. Targets, 2002, 6, 623-636.
123. Chandy, K.G.; Wulff, H.; Beeton, C.; Pennington, M.; Gutman, G.A.; Cahalan, M.D. K+ channels as targets for specific immunomodulation. Trends Pharmacol. Sci., 2004, 25, 280-289.
124. Köhler, R.; Wulff, H.; Eichler, I.; Kneifel, M.; Neumann, D.; Knorr, A.; Grgic, I.; Kampfe, D.; Si, H.; Wibawa, J.; Real, R.; Borner, K.; Brakemeier, S.; Orzechowski, H.D.; Reusch, H.P.; Paul, M.; Chandy, K.G.; Hoyer, J. Blockade of the intermediate- conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis. Circulation, 2003, 108, 1119-1125.
125. Grgic, I.; Eichler, I.; Heinau, P.; Si, H.; Brakemeier, S.; Hoyer, J.; Kohler, R. Selective blockade of the intermediate-conductance Ca2+-activated K+ channel suppresses proliferation of Ion Channels on Microglia: Therapeutic Targets for Neuroprotection microvascular and macrovascular endothelial cells and angiogenesis in vivo. Arterioscler. Thromb. Vasc. Biol., 2005, 25, 704-709.
126. Jager, H.; Dreker, T.; Buck, A.; Giehl, K.; Gress, T.; Grissmer, S. Blockage of intermediate-conductance Ca2+-activated K+ channels inhibit human pancreatic cancer cell growth in vitro. Mol. Pharmacol., 2004, 65, 630-638.
127. Tharp, D.L.; Wamhoff, B.R.; Turk, J.R.; Bowles, D.K. Upregulation of intermediate-conductance Ca2+-activated K+ channel (IKCa1) mediates phenotypic modulation of coronary smooth muscle. Am. J. Physiol. Heart Circ. Physiol., 2006, 291, H2493-H2503.
128. Mahaut-Smith, M.P.; Schlichter, L.C. Ca2+-activated K+ channels in human B lymphocytes and rat thymocytes. J. Physiol. (Lond.), 1989, 415, 69-83.
129. Ishii, T.M.; Maylie, J.; Adelman, J.P. Determinants of apamin and d-tubocurarine block in SK potassium channels. J. Biol. Chem., 1997, 272, 23195-23200.
130. Joiner, W.J.; Wang, L.Y.; Tang, M.D.; Kaczmarek, L.K. hSK4, a member of a novel subfamily of calcium-activated potassium channels. Proc. Natl. Acad. Sci. USA, 1997, 94, 11013-11018.
131. Khanna, R.; Chang, M.C.; Joiner, W.J.; Kaczmarek, L.K.; Schlichter, L.C. hSK4/hIK1, a calmodulin-binding KCa channel in human T lymphocytes: roles in proliferation and volume regulation. J. Biol. Chem., 1999, 274, 14838-14849.
132. Grissmer, S.; Nguyen, A.N.; Cahalan, M.D. Calcium-activated potassium channels in resting and activated human T lymphocytes: expression levels, calcium dependence, ion selectivity, and pharmacology. J. Gen. Physiol., 1993, 102, 601-630.
133. Logsdon, N.J.; Kang, J.; Togo, J.A.; Christian, E.P.; Aiyar, J. A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes. J. Biol. Chem., 1997, 272, 32723-32726.
134. Ghanshani, S.; Wulff, H.; Miller, M.J.; Rohm, H.; Neben, A.; Gutman, G.A.; Cahalan, M.D.; Chandy. K.G. Up-regulation of the IKCa1 potassium channel during T-cell activation: molecular mechanism and functional consequences. J. Biol. Chem., 2000, 275, 37137-37149.
135. Wulff, H.; Calabresi, P.A.; Allie, R.; Yun, S.; Pennington, M.Beeton, C.; Chandy, K.G. The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS. J. Clin. Invest., 2003, 111, 1703-1713.
136. Khanna, R.; Roy, L.; Zhu, X.; Schlichter, L.C. K+ channels and the microglial respiratory burst. Am. J. Physiol. Cell Physiol., 2001, 280, C796-C806.
137. Eder C, Klee R, Heinemann U: Pharmacological properties of Ca2+- activated K+ currents of ramified murine brain macrophages. Naunyn Schmiedebergs Arch. Pharmacol., 1997, 356, 233-239.
138. Schlichter, L.C.; Khanna, R. K+ channels and proliferation in neuroimmune cells. In: Roles of ion channels in physiopathology of nerve conduction and cell proliferation; Rouzaire-Dubois, B.; Benoit, E.; Dubois, J.M., Eds.; Trivandrum, Kerala, India: Research Signpost, 2002.
139. Kaushal, V.; Koeberla, P.D.; Wang, Y.; Schlichter, L.C. The Ca2+- activated K+ channel KCNN4/Kca3.1 contributes to microglia activation and nitric oxide-dependent neurodegeneration. J. Neurosci., 2007, 27, 234-244.
140. Wulff, H.; Miller, M.J.; Hansel, W.; Grissmer, S.; Cahalan, M.D.; Chandy, K.G. Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1: a potential immunosuppressant. Proc. Natl. Acad. Sci. USA, 2000, 97, 8151-8156.
141. Mauler, F.; Hinz, V.; Horvath, E.; Schuhmacher, J.; Hofmann, H.A.; Wirtz, S.; Hahn, M.G.; Urbahns, K. Selective intermediate- /small-conductance calcium-activated potassium channel (KCNN4) blockers are potent and effective therapeutics in experimental brain oedema and traumatic brain injury caused by acute subdural haematoma. Eur. J. Neurosci., 2004, 20, 1761-1768.
142. Reich, E.; Cui, L.; Yang, L.; Pugliese-Sivo, C.; Golovko, A.; Petro, M.; Vassileva, G.; Chu, I.; Nomeir, A.A.; Zhang, L.K.; Liang, X.Kozlowski, J.A.; Narula, S.K.; Zavodny, P.J.; Chou, C.C. Blocking ion channel KCNN4 alleviates the symptoms of experimental autoimmune encephalomyelitis in mice. Eur. J. Immunol., 2005, 35, 1027-1036.
143. McNeish, A.J.; Sandow, S.L.; Neylon, C.B.; Chen, M.X.; Dora, K.A.; Garland, C.J. Evidence for involvement of both IKCa and CNS & Neurological Disorders-Drug Targets, 2011, Vol. 10, No. 1 55 SKCa channels in hyperpolarizing responses of the rat middle cerebral artery. Stroke, 2006, 37, 1277-1282.
144. Tharp, D.L.; Bowles, D.K. The intermediate-conductance Ca2+- activated K+ channel (KCa3.1) in vascular disease. Cardiovasc. Hematol. Agents Med. Chem., 2009, 7, 1-11.
145. Köhler, R.; Kaistha, B.P.; Wulff, H. Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease. Expert Opin. Ther. Targets, 2010, 14, 143-155.
146. Blank, T.; Nijholt, I.; Kye, M.J.; Spiess, J. Small conductance Ca2+- activated K+ channels as targets of CNS drug development. Curr. Drug Targets CNS Neurol. Disord., 2004, 3, 161-167.
147. Bond, C.T.; Maylie, J.; Adelman, J.P. SK channels in excitability, pacemaking and synaptic integration. Curr. Opin. Neurobiol., 2005, 15, 305-311.
148. Pedarzani, P.; Stocker, M. Molecular and cellular basis of small- and intermediate-conductance, calcium-activated potassium channel function in the brain. Cell. Mol. Life Sci., 2008, 65, 3196-3217.
149. Schlichter, L.C.; Kaushal, V.; Moxon-Emre, I.; Sivagnanam, V.; Vincent, C. The Ca2+ activated SK3 channel is expressed in microglia in the rat striatum and contributes to microglia-mediated neurotoxicity in vitro. J. Neuroinflammation, 2010, 7, 4.
150. Kim, S.U.; de Vellis, J. Microglia in health and disease. J. Neurosci. Res., 2005, 81, 302-313.
151. Huitinga, I.; van Rooijen, N.; de Groot, C.J.A.; Uitdehaag, B.M.J.Dijkstra, C.D. Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages. J. Exp. Med., 1990, 172, 1025-1033.
152. Heppner, F.L.; Greter, M.; Marino, D.; Falsig, J.; Raivich, G.Hövelmeyer, N.; Waisman, A.; Rülicke, T.; Prinz, M.; Priller, J.Becher, B.; Aguzzi, A. Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nat. Med., 2005, 11, 146-152.
153. Kotter, M.R.; Zhao, C.; van Rooijen, N.; Franklin, R.J.M. Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression. Neurobiol. Dis., 2005, 18, 166-175.
154. Stadelmann, C.; Kerschensteiner, M.; Misgeld, T.; Brück, W.; Hohlfeld, R.; Lassmann, H. BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain, 2002, 125, 75-85.
155. Filbin, M.T. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat. Rev. Neurosci., 2003, 4, 703-713.
156. Reichert, F.; Rotshenker, S. Complement-receptor-3 and scavenger-receptor-AI/II mediated myelin phagocytosis in microglia and macrophages. Neurobiol. Dis., 2003, 12, 65-72.
157. Wyss-Coray, T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat. Med., 2006, 12, 1005-1015.
158. El Khoury, J.; Luster, A.D. Mechanisms of microglia accumulation in Alzheimer's disease: therapeutic implications. Trends Pharmacol. Sci., 2008, 29, 626-632.
159. Fan, R.; Xu, F.; Previti, M.L.; Davis, J.; Grande, A.M.; Robinson, J.K.; Van Nostrand, W.E. Minocycline reduces microglial activation and improves behavioral deficits in a transgenic model of cerebral microvascular amyloid. J. Neurosci., 2007, 27, 3057-3063.
160. Nathan, C.; Calingasan, N.; Nezezon, J.; Ding, A., Lucia, M.S.; La Perle, K.; Fuortes, M.; Lin, M., Ehrt, S.; Kwon, N.S.; Chen, J.; Vodovotz, Y.; Kipiani, K.; Beal, M.F. Protection from Alzheimer's- like disease in the mouse by genetic ablation of inducible nitric oxide synthase. J. Exp. Med., 2005, 202, 1163-1169.
161. Grathwohl, S.A.; Kälin, R.E.; Bolmont, T.; Prokop, S.; Winkelmann, G.; Kaeser, S.A.; Odenthal, J.; Radde, R.; Eldh, T.; Gandy, S.; Aguzzi, A.; Staufenbiel, M.; Mathews, P.M.; Wolburg, H.; Heppner, F.L.; Jucker, M. Formation and maintenance of Alzheimer's disease -amyloid plaques in the absence of microglia. Nat. Neurosci., 2009, 12, 1361-1363.
162. Meyer-Leuhmann, 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- plaques in a mouse model of Alzheimer's disease. Nature, 2008, 451, 720-724.
163. Town, T.; Laouar, Y.; Pittenger, C.; Mori, T.; Szekely, C.A.; Tan, J.; Duman, R.S.; Flavell, R.A. Blocking TGF-Smad2/3 innate 56 CNS & Neurological Disorders-Drug Targets, 2011, Vol. 10, No. 1 immune signaling mitigates Alzheimer-like pathology. Nat. Med., 2008, 14, 681-687.
164. Takata, K.; Kitamura, Y.; Yanagisawa, D.; Morikawa, S.; Morita, M.; Inubushi, T.; Tsuchiya, D.; Chishiro, S.; Saeki, M.; Taniguchi, T.; Shimohama, S.; Tooyama, I. Microglial transplantation increases amyloid- clearance in Alzheimer model rats. FEBS Lett., 2007, 581, 475-478.
165. Wang, Q.; Tang, X.N.; Yenari, M.A. The inflammatory response in stroke. J. Neuroimmunol., 2007, 184, 53-68.
166. Dheen, S.T.; Kaur, C.; Ling, E.A. Microglial activation and its implications in the brain diseases. Curr. Med. Chem., 2007, 14, 1189-1197.
167. Lalancette-Hébert, M.; Gowing, G.; Simard, A.; Weng, Y.C.; Kriz, J. Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. J. Neurosci., 2007, 27, 2596-2605.
168. Imai, F.; Suzuki, H.; Oda, J.; Ninomiya, T.; Ono, K.; Sano, H.; Sawada, M. Neuroprotective effect of exogenous microglia in global brain ischemia. J. Cereb. Blood Flow Metab., 2007, 27, 488-500.
169. Trapp, B.D.; Wujek, J.R.; Criste, G.A.; Jalabi, W.; Yin, X.; Kidd, G.J.; Stohlman, S.; Ransohoff, R. Evidence for synaptic stripping by cortical microglia. Glia, 2007, 55, 360-368.
170. Rappert, A.; Bechmann, I.; Pivneva, T.; Mahlo, J.; Biber, K.; Nolte, C.; Kovac, A.D.; Gerard, C.; Boddeke, H.W.; Nitsch, R.; Kettenmann, H. CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion. J. Neurosci., 2004, 24, 8500-8509. Stephen D. Skaper
171. McGeer, P.L.; McGeer, E.G. Inflammation, autotoxicity and Alzheimer disease. Neurobiol. Aging, 2001, 22, 799-809.
172. Eikelenboom, P.; Bate, C.; Van Gool, W.A.; Hoozemans, J.J.; Rozemuller, J.M.; Veerhuis, R.; Williams, A. Neuroinflammation in Alzheimer's disease and prion disease. Glia, 2002, 40, 232-239.
173. Golde, S.; Chandran, S.; Brown, G.C.; Compston, A. Different pathways for iNOS-mediated toxicity in vitro dependent on neuronal maturation and NMDA receptor expression. J. Neurochem., 2002, 82, 269-282.
174. Diemel, L.T.; Copelman, C.A.; Cuzner, M.L. Macrophages in CNS remyelination: friend or foe? Neurochem. Res., 1998, 23, 341-347.
175. Giulian, D. Microglia and the immune pathology of Alzheimer disease. Am. J. Hum. Genet., 1999, 65, 13-18.
176. Kaul, M.; Garden, G.A.; Lipton, S.A. Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature, 2001, 410, 988-994.
177. Heneka, M.T; Nadrigny, F.; Regen, T.; Martinez-Hernandez, A.; Dumitrescu-Ozimek, L.; Terwel, D.; Jardanhazi-Kurutz, D.; Walter, J.; Kirchhoff, F.; Hanisch, U.K.; Kummer, M.P. Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine. Proc. Natl. Acad. Sci. USA, 2010, 107, 6058-6063.
178. Fuhrmann, M.; Bittner, T.; Jung, C.K.; Burgold, S.; Page, R.M.; Mitteregger, G.; Haass, C.; LaFerla, F.M.; Kretzschmar, H.; Herms, J. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nat. Neurosci., 2010, 13, 411-413.