P2Y receptors in Alzheimer's disease

Biology of the Cell

Volumn 107, Issue 1, 2015, Pages 1-21

  Erb, Laurie ^a   Cao, Chen ^a   Ajit, Deepa ^a   Weisman, Gary A ^a  

^a University of Missouri   (United States)

Author keywords

Alzheimer's disease; Neuroinflammation; Neurovascular Regulation; P2Y receptors; Purinergic receptors

Indexed keywords

AMYLOID BETA PROTEIN; PURINERGIC P2Y RECEPTOR;

ALZHEIMER DISEASE; ANIMAL; BRAIN; DISEASE MODEL; GENETICS; HUMAN; METABOLISM; MOUSE; MULTIGENE FAMILY;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; BRAIN; DISEASE MODELS, ANIMAL; HUMANS; MICE; MULTIGENE FAMILY; RECEPTORS, PURINERGIC P2Y;

EID: 84920165130     PISSN: 02484900     EISSN: 1768322X     Source Type: Journal    
DOI: 10.1111/boc.201400043     Document Type: Article

References (231)

1. Agresti, C., Meomartini, M.E., Amadio, S., Ambrosini, E., Volonte, C., Aloisi, F. and Visentin, S. (2005) ATP regulates oligodendrocyte progenitor migration, proliferation, and differentiation: involvement of metabotropic P2 receptors. Brain Res. Brain Res. Rev. 48, 157-165
2. Aizawa, H., Wakatsuki, S., Ishii, A., Moriyama, K., Sasaki, Y., Ohashi, K., Sekine-Aizawa, Y., Sehara-Fujisawa, A., Mizuno, K., Goshima, Y. and Yahara, I. (2001) Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse. Nat. Neurosci. 4, 367-373
3. 2 nucleotide receptors enhances early pathology in the TgCRND8 mouse model of Alzheimer's disease. Mol. Neurobiol. 49, 1031-1042
4. Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G.M., Cooper, N.R., Eikelenboom, P., Emmerling, M., Fiebich, B.L. (2000) Inflammation and Alzheimer's disease. Neurobiol. Aging 21, 383-421
5. Alsop, D.C., Detre, J.A. and Grossman, M. (2000) Assessment of cerebral blood flow in Alzheimer's disease by spin-labeled magnetic resonance imaging. Ann. Neurol. 47, 93-100
6. 12 receptor protein in cortical gray matter lesions in multiple sclerosis. Cereb. Cortex 20, 1263-1273
7. Amadio, S., Montilli, C., Picconi, B., Calabresi, P. and Volonte, C. (2007) Mapping P2X and P2Y receptor proteins in striatum and substantia nigra: an immunohistological study. Purinergic Signal. 3, 389-398
8. 12 metabotropic receptor in adult rat brain. Neuroscience 141, 1171-1180
9. Arthur, D.B., Akassoglou, K. and Insel, P.A. (2005) P2Y2 receptor activates nerve growth factor/TrkA signaling to enhance neuronal differentiation. Proc. Natl. Acad. Sci. U.S.A. 102, 19138-19143
10. Backstrom, J.R., Lim, G.P., Cullen, M.J. and Tokes, Z.A. (1996) Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-beta peptide (1-40). J. Neurosci. 16, 7910-7919
11. 2 nucleotide receptor interacts with alphaV integrins to activate Go and induce cell migration. J. Biol. Chem. 280, 39050-39057
12. Bamberger, M.E., Harris, M.E., McDonald, D.R., Husemann, J. and Landreth, G.E. (2003) A cell surface receptor complex for fibrillar beta-amyloid mediates microglial activation. J. Neurosci. 23, 2665-2674
13. Barone, E., Di Domenico, F., Sultana, R., Coccia, R., Mancuso, C., Perluigi, M. and Butterfield, D.A. (2012) Heme oxygenase-1 posttranslational modifications in the brain of subjects with Alzheimer disease and mild cognitive impairment. Free Radic. Biol. Med. 52, 2292-2301
14. Beigi, R., Kobatake, E., Aizawa, M. and Dubyak, G.R. (1999) Detection of local ATP release from activated platelets using cell surface-attached firefly luciferase. Am. J. Physiol. 276, C267-278
15. Bell, R.D., Deane, R., Chow, N., Long, X., Sagare, A., Singh, I., Streb, J.W., Guo, H., Rubio, A., Van Nostrand, W. (2009) SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells. Nat. Cell Biol. 11, 143-153
16. Bell, R.D. and Zlokovic, B.V. (2009) Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease. Acta Neuropathol. 118, 103-113
17. 6 receptors on monocytes is required for TLR1/2-induced neutrophil migration by regulating IL-8 secretion. Eur. J. Immunol. 39, 2885-2894
18. Bennett, G.C. and Boarder, M.R. (2000) The effect of nucleotides and adenosine on stimulus-evoked glutamate release from rat brain cortical slices. Br. J. Pharmacol. 131, 617-623
19. Bergfeld, G.R. and Forrester, T. (1992) Release of ATP from human erythrocytes in response to a brief period of hypoxia and hypercapnia. Cardiovasc. Res. 26, 40-47
20. Boche, D., Denham, N., Holmes, C. and Nicoll, J.A. (2010) Neuropathology after active Abeta42 immunotherapy: implications for Alzheimer's disease pathogenesis. Acta Neuropathol. 120, 369-384
21. Bodin, P. and Burnstock, G. (1995) Synergistic effect of acute hypoxia on flow-induced release of ATP from cultured endothelial cells. Experientia 51, 256-259
22. Bolmont, T., Haiss, F., Eicke, D., Radde, R., Mathis, C.A., Klunk, W.E., Kohsaka, S., Jucker, M. and Calhoun, M.E. (2008) Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J. Neurosci. 28, 4283-4292
23. Brayden, J.E. (1991) Hyperpolarization and relaxation of resistance arteries in response to adenosine diphosphate. Distribution and mechanism of action. Circ. Res. 69, 1415-1420
24. Bruce-Keller, A.J., Gupta, S., Parrino, T.E., Knight, A.G., Ebenezer, P.J., Weidner, A.M., LeVine, H. III, Keller, J.N. and Markesbery, W.R. (2010) NOX activity is increased in mild cognitive impairment. Antioxid. Redox Signal. 12, 1371-1382
25. 2 nucleotide receptors inhibit trauma-induced death of astrocytic cells. J. Neurochem. 103, 1785-1800
26. Burnstock, G. (2008). Purinergic signalling and disorders of the central nervous system. Nat. Rev. Drug Discov. 7, 575-590
27. Burnstock, G. and Knight, G.E. (2004) Cellular distribution and functions of P2 receptor subtypes in different systems. Int. Rev. Cytol. 240, 31-304
28. Burnstock, G. and Ralevic, V. (2014) Purinergic signaling and blood vessels in health and disease. Pharmacol. Rev. 66, 102-192
29. 2 receptors are coupled to the NO/cGMP pathway to vasodilate the rat arterial mesenteric bed. Br. J. Pharmacol. 136, 847-856
30. Cacabelos, R., Alvarez, X.A., Fernandez-Novoa, L., Franco, A., Mangues, R., Pellicer, A. and Nishimura, T. (1994) Brain interleukin-1 beta in Alzheimer's disease and vascular dementia. Methods Find. Exp. Clin. Pharmacol. 16, 141-151
31. Caccamo, A., Oddo, S., Billings, L.M., Green, K.N., Martinez-Coria, H., Fisher, A. and LaFerla, F.M. (2006) M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron 49, 671-682
32. 6 and atypical UTP-sensitive receptors coupled to rises in intracellular calcium in mouse cultured superior cervical ganglion neurons and glia. Br. J. Pharmacol. 143, 525-532
33. 2 nucleotide receptors enhance alpha-secretase-dependent amyloid precursor protein processing. J. Biol. Chem. 280, 18696-18702
34. Chakfe, Y., Seguin, R., Antel, J.P., Morissette, C., Malo, D., Henderson, D. and Seguela, P. (2002) ADP and AMP induce interleukin-1beta release from microglial cells through activation of ATP-primed P2X7 receptor channels. J. Neurosci. 22, 3061-3069
35. 2 receptor sensitizes mouse bladder sensory neurons and facilitates purinergic currents. J. Neurosci. 30, 2365-2372
36. 1 receptors in cognitive deficit after focal cerebral stroke in a rodent model. J. Neuroinflammation 10, 95
37. Choi, H.B., Ryu, J.K., Kim, S.U. and McLarnon, J.G. (2007) Modulation of the purinergic P2X7 receptor attenuates lipopolysaccharide-mediated microglial activation and neuronal damage in inflamed brain. J. Neurosci. 27, 4957-4968
38. Chorna, N.E., Santiago-Perez, L.I., Erb, L., Seye, C.I., Neary, J.T., Sun, G.Y., Weisman, G.A. and Gonzalez, F.A. (2004) P2Y receptors activate neuroprotective mechanisms in astrocytic cells. J. Neuroschem. 91, 119-132
39. Chow, N., Bell, R.D., Deane, R., Streb, J.W., Chen, J., Brooks, A., Van Nostrand, W., Miano, J.M. and Zlokovic, B.V. (2007) Serum response factor and myocardin mediate arterial hypercontractility and cerebral blood flow dysregulation in Alzheimer's phenotype. Proc. Natl. Acad. Sci. U.S.A. 104, 823-828
40. Claudio, L. (1996) Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer's disease patients. Acta Neuropathol. 91, 6-14
41. Costa-Mattioli, M., Sossin, W.S., Klann, E. and Sonenberg, N. (2009) Translational control of long-lasting synaptic plasticity and memory. Neuron 61, 10-26
42. Csolle, C., Heinrich, A., Kittel, A. and Sperlagh, B. (2008) P2Y receptor mediated inhibitory modulation of noradrenaline release in response to electrical field stimulation and ischemic conditions in superfused rat hippocampus slices. J. Neurochem. 106, 347-360
43. Cunha, R.A., Ribeiro, J.A. and Sebastiao, A.M. (1994) Purinergic modulation of the evoked release of [3H]acetylcholine from the hippocampus and cerebral cortex of the rat: role of the ectonucleotidases. Eur. J. Neurosci. 6, 33-42
44. 2 receptor mRNA in astrocytes cultured from rat brain. Int. J. Immunopathol. Pharmacol. 20, 301-316
45. 6 receptor architecture in native and transfected neuronal systems. Biochim. Biophys. Acta 1768, 1592-1599
46. Davalos, D., Grutzendler, J., Yang, G., Kim, J.V., Zuo, Y., Jung, S., Littman, D.R., Dustin, M.L. and Gan, W.B. (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8, 752-758
47. De Lorenzo, S., Veggetti, M., Muchnik, S. and Losavio, A. (2006) Presynaptic inhibition of spontaneous acetylcholine release mediated by P2Y receptors at the mouse neuromuscular junction. Neuroscience 142, 71-85
48. 13 and ATP-gated P2X7 receptors on axonal elongation. J. Cell Sci. 125, 176-188
49. Deuss, M., Reiss, K. and Hartmann, D. (2008) Part-time alpha-secretases: the functional biology of ADAM 9, 10 and 17. Curr. Alzheimer Res. 5, 187-201
50. Dietrich, H.H., Horiuchi, T., Xiang, C., Hongo, K., Falck, J.R. and Dacey, R.G. Jr. (2009) Mechanism of ATP-induced local and conducted vasomotor responses in isolated rat cerebral penetrating arterioles. J. Vascular Res. 46, 253-264
51. Dietrich, H.H., Xiang, C., Han, B.H., Zipfel, G.J. and Holtzman, D.M. (2010) Soluble amyloid-beta, effect on cerebral arteriolar regulation and vascular cells. Mol. Neurodegener. 5, 15
52. 12 receptor in platelet activation. J. Clin. Invest. 113, 340-345
53. Elliott, M.R., Chekeni, F.B., Trampont, P.C., Lazarowski, E.R., Kadl, A., Walk, S.F., Park, D., Woodson, R.I., Ostankovich, M., Sharma, P. (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461, 282-286
54. Eltzschig, H.K., Eckle, T., Mager, A., Kuper, N., Karcher, C., Weissmuller, T., Boengler, K., Schulz, R., Robson, S.C. and Colgan, S.P. (2006) ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ. Res. 99, 1100-1108
55. Endo, M., Ohashi, K. and Mizuno, K. (2007) LIM kinase and slingshot are critical for neurite extension. J. Biol. Chem. 282, 13692-13702
56. Endo, M., Ohashi, K., Sasaki, Y., Goshima, Y., Niwa, R., Uemura, T. and Mizuno, K. (2003) Control of growth cone motility and morphology by LIM kinase and Slingshot via phosphorylation and dephosphorylation of cofilin. J. Neurosci. 23, 2527-2537
57. Erlinge, D. and Burnstock, G. (2008) P2 receptors in cardiovascular regulation and disease. Purinergic Signal. 4, 1-20
58. 13 receptor activates the Nrf2/HO-1 axis and protects against oxidative stress-induced neuronal death. Free Radic. Biol. Med. 49, 416-426
59. Farias, M. 3rd, Gorman, M.W., Savage, M.V. and Feigl, E.O. (2005) Plasma ATP during exercise: possible role in regulation of coronary blood flow. Am. J. Physiol. Heart Circ. Physiol. 288, H1586-1590
60. Fiala, M., Zhang, L., Gan, X., Sherry, B., Taub, D., Graves, M.C., Hama, S., Way, D., Weinand, M., Witte, M. (1998) Amyloid-beta induces chemokine secretion and monocyte migration across a human blood-brain barrier model. Mol. Med. 4, 480-489
61. Figge, C., Loers, G., Schachner, M. and Tilling, T. (2012) Neurite outgrowth triggered by the cell adhesion molecule L1 requires activation and inactivation of the cytoskeletal protein cofilin. Mol. Cell. Neurosci. 49, 196-204
62. Forrester, T. (1978) Extracellular nucleotides in exercise: possible effect on brain metabolism. J. Physiol. (Paris) 74, 477-483
63. Forrester, T., Harper, A.M., MacKenzie, E.T. and Thomson, E.M. (1979) Effect of adenosine triphosphate and some derivatives on cerebral blood flow and metabolism. J. Physiol. 296, 343-355
64. Franke, H., Krugel, U., Grosche, J., Heine, C., Hartig, W., Allgaier, C. and Illes, P. (2004) P2Y receptor expression on astrocytes in the nucleus accumbens of rats. Neuroscience 127, 431-441
65. Frautschy, S.A., Yang, F., Irrizarry, M., Hyman, B., Saido, T.C., Hsiao, K. and Cole, G.M. (1998) Microglial response to amyloid plaques in APPsw transgenic mice. Am. J. Pathol. 152, 307-317
66. Fujita, T., Tozaki-Saitoh, H. and Inoue, K. (2009) P2Y1 receptor signaling enhances neuroprotection by astrocytes against oxidative stress via IL-6 release in hippocampal cultures. Glia 57, 244-257
67. Griffin, W.S. (2006) Inflammation and neurodegenerative diseases. Am. J. Clin. Nutr. 83, 470S-474S
68. Guns, P.J., Korda, A., Crauwels, H.M., Van Assche, T., Robaye, B., Boeynaems, J.M. and Bult, H. (2005) Pharmacological characterization of nucleotide P2Y receptors on endothelial cells of the mouse aorta. Br. J. Pharmacol. 146, 288-295
69. Guns, P.J., Van Assche, T., Fransen, P., Robaye, B., Boeynaems, J.M. and Bult, H. (2006) Endothelium-dependent relaxation evoked by ATP and UTP in the aorta of P2Y2-deficient mice. Br. J. Pharmacol. 147, 569-574
70. Haass, C. and Selkoe, D.J. (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat. Rev. Mol. Cell Biol. 8, 101-112
71. Hao, W., Liu, Y., Liu, S., Walter, S., Grimm, M.O., Kiliaan, A.J., Penke, B., Hartmann, T., Rube, C.E., Menger, M.D. and Fassbender, K. (2011) Myeloid differentiation factor 88-deficient bone marrow cells improve Alzheimer's disease-related symptoms and pathology. Brain 134, 278-292
72. Hardebo, J.E., Kahrstrom, J., Owman, C. and Salford, L.G. (1987) Endothelium-dependent relaxation by uridine tri- and diphosphate in isolated human pial vessels. Blood Vessels 24, 150-155
73. Hashimoto, M., Shinozuka, K., Tanabe, Y., Gamoh, S., Hara, T., Hossain, M.S., Kwon, Y.M., Kunitomo, M. and Masumura, S. (1999) Hypotension induced by exercise is associated with enhanced release of adenyl purines from aged rat artery. Am. J. Physiol. 276, H970-H975
74. 12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9, 1512-1519
75. Heine, C., Wegner, A., Grosche, J., Allgaier, C., Illes, P. and Franke, H. (2007) P2 receptor expression in the dopaminergic system of the rat brain during development. Neuroscience 149, 165-181
76. Hernandez-Guillamon, M., Delgado, P., Ortega, L., Pares, M., Rosell, A., Garcia-Bonilla, L., Fernandez-Cadenas, I., Borrell-Pages, M., Boada, M. and Montaner, J. (2009) Neuronal TIMP-1 release accompanies astrocytic MMP-9 secretion and enhances astrocyte proliferation induced by beta-amyloid 25-35 fragment. J. Neurosci. Res. 87, 2115-2125
77. Higuchi, M., Zhang, B., Forman, M.S., Yoshiyama, Y., Trojanowski, J.Q. and Lee, V.M. (2005) Axonal degeneration induced by targeted expression of mutant human tau in oligodendrocytes of transgenic mice that model glial tauopathies. J. Neurosci. 25, 9434-9443
78. Hisada, T., Ayaori, M., Ohrui, N., Nakashima, H., Nakaya, K., Uto-Kondo, H., Yakushiji, E., Takiguchi, S., Terao, Y., Miyamoto, Y. (2012) Statin inhibits hypoxia-induced endothelin-1 via accelerated degradation of HIF-1alpha in vascular smooth muscle cells. Cardiovasc. Res. 95, 251-259
79. Ho, G.J., Drego, R., Hakimian, E. and Masliah, E. (2005) Mechanisms of cell signaling and inflammation in Alzheimer's disease. Curr. Drug Targets Inflamm. Allergy 4, 247-256
80. Honda, S., Sasaki, Y., Ohsawa, K., Imai, Y., Nakamura, Y., Inoue, K. and Kohsaka, S. (2001) Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J. Neurosci. 21, 1975-1982
81. Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F. and Cole, G. (1996) Correlative memory deficits, Abeta elevation and amyloid plaques in transgenic mice. Science 274, 99-102
82. Iadecola, C. (2004) Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat. Rev. Neurosci. 5, 347-360
83. Iadecola, C., Zhang, F., Niwa, K., Eckman, C., Turner, S.K., Fischer, E., Younkin, S., Borchelt, D.R., Hsiao, K.K. and Carlson, G.A. (1999) SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat. Neurosci. 2, 157-161
84. Jantzen, H.M., Gousset, L., Bhaskar, V., Vincent, D., Tai, A., Reynolds, E.E. and Conley, P.B. (1999) Evidence for two distinct G-protein-coupled ADP receptors mediating platelet activation. Thromb. Haemost. 81, 111-117
85. Jiang, Q., Lee, C.Y., Mandrekar, S., Wilkinson, B., Cramer, P., Zelcer, N., Mann, K., Lamb, B., Willson, T.M., Collins, J.L. (2008) ApoE promotes the proteolytic degradation of Abeta. Neuron 58, 681-693
86. Jimenez, E., Zafra, F., Perez-Sen, R., Delicado, E.G., Miras-Portugal, M.T., Aragon, C. and Lopez-Corcuera, B. (2011) P2Y purinergic regulation of the glycine neurotransmitter transporters. J. Biol. Chem. 286, 10712-10724
87. Kawarabayashi, T., Younkin, L.H., Saido, T.C., Shoji, M., Ashe, K.H. and Younkin, S.G. (2001) Age-dependent changes in brain, CSF and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J. Neurosci. 21, 372-381
88. Kelleher, R.J. and Soiza, R.L. (2013) Evidence of endothelial dysfunction in the development of Alzheimer's disease: is Alzheimer's a vascular disorder? Am. J. Cardiovasc. Dis. 3, 197-226
89. Kennedy, C. and Burnstock, G. (1985) ATP produces vasodilation via P1 purinoceptors and vasoconstriction via P2 purinoceptors in the isolated rabbit central ear artery. Blood Vessels 22, 145-155
90. 4 receptor. Mol. Pharmacol. 57, 926-931
91. 6 receptor. J. Immunol. 186, 3701-3709
92. 2 receptor activation. J. Neurochem. 121, 228-238
93. 14-receptor-mediated signal(s). Cell. Mol. Neurobiol. 33, 47-58
94. Klegeris, A., McGeer, E.G. and McGeer, P.L. (2007) Therapeutic approaches to inflammation in neurodegenerative disease. Curr. Opin. Neurol. 20, 351-357
95. Kobayashi, K., Fukuoka, T., Yamanaka, H., Dai, Y., Obata, K., Tokunaga, A. and Noguchi, K. (2006) Neurons and glial cells differentially express P2Y receptor mRNAs in the rat dorsal root ganglion and spinal cord. J. Comp. Neurol. 498, 443-454
96. Koch, H., von Kugelgen, I. and Starke, K. (1997) P2-receptor-mediated inhibition of noradrenaline release in the rat hippocampus. Naunyn Schmiedebergs Arch. Pharmacol. 355, 707-715
97. Koenigsknecht, J. and Landreth, G. (2004) Microglial phagocytosis of fibrillar beta-amyloid through a beta1 integrin-dependent mechanism. J. Neurosci. 24, 9838-9846
98. Kohama, S.G., Rosene, D.L. and Sherman, L.S. (2012) Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline. Age 34, 1093-1110
99. 6 receptors is a mediator of microglial phagocytosis. Nature 446, 1091-1095
100. Koles, L., Leichsenring, A., Rubini, P. and Illes, P. (2011) P2 receptor signaling in neurons and glial cells of the central nervous system. Adv. Pharmacol. 61, 441-493
101. Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E. and Tanaka, K. (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880-884
102. 2 receptor. J. Neurochem. 109, 1300-1310
103. 2 nucleotide receptor mRNA expression is an immediate early gene response in activated thymocytes. Proc. Natl. Acad. Sci. U.S.A. 94, 831-836
104. Krugel, U., Kittner, H. and Illes, P. (1999) Adenosine 5′-triphosphate-induced dopamine release in the rat nucleus accumbens in vivo. Neurosci. Lett. 265, 49-52
105. Krugel, U., Kittner, H. and Illes, P. (2001) Mechanisms of adenosine 5′-triphosphate-induced dopamine release in the rat nucleus accumbens in vivo. Synapse 39, 222-232
106. 1 receptor is involved in the regulation of cytokine/chemokine transcription and cerebral damage in a rat model of cerebral ischemia. J. Cereb. Blood Flow Metab. 31, 1930-1941
107. Kuhn, P.H., Wang, H., Dislich, B., Colombo, A., Zeitschel, U., Ellwart, J.W., Kremmer, E., Rossner, S. and Lichtenthaler, S.F. (2010) ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. EMBO J. 29, 3020-3032
108. Lacar, B., Herman, P., Platel, J.C., Kubera, C., Hyder, F. and Bordey, A. (2012) Neural progenitor cells regulate capillary blood flow in the postnatal subventricular zone. J. Neurosci. 32, 16435-16448
109. Lai, M.K., Tan, M.G., Kirvell, S., Hobbs, C., Lee, J., Esiri, M.M., Chen, C.P. and Francis, P.T. (2008) Selective loss of P2Y2 nucleotide receptor immunoreactivity is associated with Alzheimer's disease neuropathology. J. Neural Transm. 115, 1165-1172
110. Lee, Y.J., Han, S.B., Nam, S.Y., Oh, K.W. and Hong, J.T. (2010) Inflammation and Alzheimer's disease. Arch. Pharm. Res. 33, 1539-1556
111. 2 nucleotide receptors on alpha-secretase-dependent APP processing in Neuro-2a cells. FEBS Lett. 585, 2255-2262
112. 4 receptor-mediated pinocytosis contributes to amyloid beta-induced self-uptake by microglia. Mol. Cell Biol. 33, 4282-4293
113. Lichtenthaler, S.F. (2012) Alpha-secretase cleavage of the amyloid precursor protein: proteolysis regulated by signaling pathways and protein trafficking. Curr. Alzheimer Res. 9, 165-177
114. Liu, F., Iqbal, K., Grundke-Iqbal, I., Rossie, S. and Gong, C.X. (2005) Dephosphorylation of tau by protein phosphatase 5: impairment in Alzheimer's disease. J. Biol. Chem. 280, 1790-1796
115. Liu, X.B., Shen, Y., Plane, J.M. and Deng, W. (2013) Vulnerability of premyelinating oligodendrocytes to white-matter damage in neonatal brain injury. Neurosci. Bull. 29, 229-238
116. Lorenzl, S., Albers, D.S., Relkin, N., Ngyuen, T., Hilgenberg, S.L., Chirichigno, J., Cudkowicz, M.E. and Beal, M.F. (2003) Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer's disease. Neurochem. Int. 43, 191-196
117. Lustig, K.D., Erb, L., Landis, D.M., Hicks-Taylor, C.S., Zhang, X., Sportiello, M.G. and Weisman, G.A. (1992) Mechanisms by which extracellular ATP and UTP stimulate the release of prostacyclin from bovine pulmonary artery endothelial cells. Biochim. Biophys. Acta 1134, 61-72
118. 1 receptor activation inhibits NMDA receptor-channels in layer V pyramidal neurons of the rat prefrontal and parietal cortex. Neurochem. Int. 42, 161-172
119. Ma, T., Trinh, M.A., Wexler, A.J., Bourbon, C., Gatti, E., Pierre, P., Cavener, D.R. and Klann, E. (2013) Suppression of eIF2alpha kinases alleviates Alzheimer's disease-related plasticity and memory deficits. Nat. Neurosci. 16, 1299-1305
120. Malin, S.A. and Molliver, D.C. (2010) Gi- and Gq-coupled ADP (P2Y) receptors act in opposition to modulate nociceptive signaling and inflammatory pain behavior. Mol. Pain 6, 21
121. 6 receptor mediated contractions in human cerebral arteries. BMC Pharmacol. 3, 4
122. Mandrekar, S., Jiang, Q., Lee, C.Y., Koenigsknecht-Talboo, J., Holtzman, D.M. and Landreth, G.E. (2009) Microglia mediate the clearance of soluble Abeta through fluid phase macropinocytosis. J. Neurosci. 29, 4252-4262
123. Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S.W. and Bates, G.P. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493-506
124. Mao, P. and Reddy, P.H. (2011) Aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction in Alzheimer's disease: implications for early intervention and therapeutics. Biochim. Biophys. Acta 1812, 1359-1370
125. Matsumoto, Y., Yanase, D., Noguchi-Shinohara, M., Ono, K., Yoshita, M. and Yamada, M. (2007) Blood-brain barrier permeability correlates with medial temporal lobe atrophy but not with amyloid-beta protein transport across the blood-brain barrier in Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 23, 241-245
126. Mayeux, R. and Stern, Y. (2012) Epidemiology of Alzheimer disease. Cold Spring Harb. Perspect. Med. 2, a006239
127. McGeer, E.G., Klegeris, A. and McGeer, P.L. (2005) Inflammation, the complement system and the diseases of aging. Neurobiol. Aging 26 (Suppl 1), 94-97
128. Mead, E.L., Mosley, A., Eaton, S., Dobson, L., Heales, S.J. and Pocock, J.M. (2012) Microglial neurotransmitter receptors trigger superoxide production in microglia; consequences for microglial-neuronal interactions. J. Neurochem. 121, 287-301
129. Meberg, P.J. and Bamburg, J.R. (2000) Increase in neurite outgrowth mediated by overexpression of actin depolymerizing factor. J. Neurosci. 20, 2459-2469
130. Meberg, P.J., Ono, S., Minamide, L.S., Takahashi, M. and Bamburg, J.R. (1998) Actin depolymerizing factor and cofilin phosphorylation dynamics: response to signals that regulate neurite extension. Cell. Motil. Cytoskeleton 39, 172-190
131. Mendoza-Fernandez, V., Andrew, R.D. and Barajas-Lopez, C. (2000) ATP inhibits glutamate synaptic release by acting at P2Y receptors in pyramidal neurons of hippocampal slices. J. Pharmacol. Exp. Ther. 293, 172-179
132. Meyer-Luehmann, M., Spires-Jones, T.L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., Koenigsknecht-Talboo, J., Holtzman, D.M., Bacskai, B.J. and Hyman, B.T. (2008) Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 451, 720-724
133. Miao, L.Y., Tang, J.P., Esposito, D.P. and Zhang, J.H. (2001) Age-related changes in P2 receptor mRNA of rat cerebral arteries. Exp. Gerontol. 37, 67-79
134. Mingam, R., De Smedt, V., Amedee, T., Bluthe, R.M., Kelley, K.W., Dantzer, R. and Laye, S. (2008) In vitro and in vivo evidence for a role of the P2X7 receptor in the release of IL-1 beta in the murine brain. Brain Behav. Immun. 22, 234-244
135. Mishra, S.K., Braun, N., Shukla, V., Fullgrabe, M., Schomerus, C., Korf, H.W., Gachet, C., Ikehara, Y., Sevigny, J., Robson, S.C. and Zimmermann, H. (2006) Extracellular nucleotide signaling in adult neural stem cells: synergism with growth factor-mediated cellular proliferation. Development 133, 675-684
136. Misiti, F., Orsini, F., Clementi, M.E., Masala, D., Tellone, E., Galtieri, A. and Giardina, B. (2008) Amyloid peptide inhibits ATP release from human erythrocytes. Biochem. Cell Biol. 86, 501-508
137. Miyagi, Y., Kobayashi, S., Nishimura, J., Fukui, M. and Kanaide, H. (1996) Dual regulation of cerebrovascular tone by UTP: P2U receptor-mediated contraction and endothelium-dependent relaxation. Br. J. Pharmacol. 118, 847-856
138. Mizoguchi, H., Takuma, K., Fukuzaki, E., Ibi, D., Someya, E., Akazawa, K.H., Alkam, T., Tsunekawa, H., Mouri, A., Noda, Y. (2009) Matrix metalloprotease-9 inhibition improves amyloid beta-mediated cognitive impairment and neurotoxicity in mice. J. Pharmacol. Exp. Ther. 331, 14-22
139. Monsonego, A. and Weiner, H.L. (2003) Immunotherapeutic approaches to Alzheimer's disease. Science 302, 834-838
140. 1 purinergic receptor in the human brain: striking neuronal localisation. J. Comp. Neurol. 421, 374-384
141. 1 purinergic receptor in Alzheimer's disease. Neuroreport 11, 3799-3803
142. Moore, D.J., Chambers, J.K., Wahlin, J.P., Tan, K.B., Moore, G.B., Jenkins, O., Emson, P.C. and Murdock, P.R. (2001) Expression pattern of human P2Y receptor subtypes: a quantitative reverse transcription-polymerase chain reaction study. Biochim. Biophys. Acta 1521, 107-119
143. 1 purinergic receptor in neurons and glial cells of the central nervous system. Brain Res. Mol. Brain Res. 78, 50-58
144. Nasu-Tada, K., Koizumi, S. and Inoue, K. (2005) Involvement of beta1 integrin in microglial chemotaxis and proliferation on fibronectin: different regulations by ADP through PKA. Glia 52, 98-107
145. Neary, J.T., Kang, Y., Willoughby, K.A. and Ellis, E.F. (2003) Activation of extracellular signal-regulated kinase by stretch-induced injury in astrocytes involves extracellular ATP and P2 purinergic receptors. J. Neurosci. 23, 2348-2356
146. Nicoll, J.A., Wilkinson, D., Holmes, C., Steart, P., Markham, H. and Weller, R.O. (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat. Med. 9, 448-452
147. Niwa, K., Carlson, G.A. and Iadecola, C. (2000a) Exogenous A beta1-40 reproduces cerebrovascular alterations resulting from amyloid precursor protein overexpression in mice. J. Cereb. Blood Flow Metab. 20, 1659-1668
148. Niwa, K., Younkin, L., Ebeling, C., Turner, S.K., Westaway, D., Younkin, S., Ashe, K.H., Carlson, G.A. and Iadecola, C. (2000b) Abeta 1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation. Proc. Natl. Acad. Sci. U.S.A. 97, 9735-9740
149. Niwa, K., Porter, V.A., Kazama, K., Cornfield, D., Carlson, G.A. and Iadecola, C. (2001) A beta-peptides enhance vasoconstriction in cerebral circulation. Am. J. Physiol .Heart Circ. Physiol. 281, H2417-2424
150. Niwa, K., Kazama, K., Younkin, L., Younkin, S.G., Carlson, G.A. and Iadecola, C. (2002) Cerebrovascular autoregulation is profoundly impaired in mice overexpressing amyloid precursor protein. Am. J. Physiol. Heart Circ. Physiol. 283, H315-323
151. O'Brien, R.J. and Wong, P.C. (2011) Amyloid precursor protein processing and Alzheimer's disease. Ann. Rev. Neurosci. 34, 185-204
152. Obulesu, M., Venu, R. and Somashekhar, R. (2011) Tau mediated neurodegeneration: an insight into Alzheimer's disease pathology. Neurochem. Res. 36, 1329-1335
153. Ortega, F., Perez-Sen, R. and Miras-Portugal, M.T. (2008) Gi-coupled P2Y-ADP receptor mediates GSK-3 phosphorylation and beta-catenin nuclear translocation in granule neurons. J. Neurochem. 104, 62-73
154. Paris, D., Humphrey, J., Quadros, A., Patel, N., Crescentini, R., Crawford, F. and Mullan, M. (2003) Vasoactive effects of A beta in isolated human cerebrovessels and in a transgenic mouse model of Alzheimer's disease: role of inflammation. Neurol. Res. 25, 642-651
155. Perlmutter, L.S., Barron, E. and Chui, H.C. (1990) Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease. Neurosci. Lett. 119, 32-36
156. 2 nucleotide receptor-mediated responses in brain cells. Mol. Neurobiol. 41, 356-366
157. 2 nucleotide receptor mediate neurite extension in IL-1beta-treated mouse primary cortical neurons. J. Neurochem. 125, 885-896
158. Pettersson, A.F., Engardt, M. and Wahlund, L.O. (2002) Activity level and balance in subjects with mild Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 13, 213-216
159. Piccini, A., Carta, S., Tassi, S., Lasiglie, D., Fossati, G. and Rubartelli, A. (2008) ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1beta and IL-18 secretion in an autocrine way. Proc. Natl. Acad. Sci. U.S.A. 105, 8067-8072
160. Pichiule, P., Chavez, J.C., Schmidt, A.M. and Vannucci, S.J. (2007) Hypoxia-inducible factor-1 mediates neuronal expression of the receptor for advanced glycation end products following hypoxia/ischemia. J. Biol. Chem. 282, 36330-36340
161. Pratico, D. (2008) Oxidative stress hypothesis in Alzheimer's disease: a reappraisal. Trends Pharmacol. Sci. 29, 609-615
162. Price, G.D., Robertson, S.J. and Edwards, F.A. (2003) Long-term potentiation of glutamatergic synaptic transmission induced by activation of presynaptic P2Y receptors in the rat medial habenula nucleus. Eur. J. Neurosci. 17, 844-850
163. Pull, I. and McIlwain, H. (1972) Adenine derivatives as neurohumoral agents in the brain. The quantities liberated on excitation of superfused cerebral tissues. Biochem. J. 130, 975-981
164. Rahman, A. (2009) The role of adenosine in Alzheimer's disease. Curr. Neuropharmacol. 7, 207-216
165. Ralevic, V. and Burnstock, G. (1996) Relative contribution of P2U- and P2Y-purinoceptors to endothelium-dependent vasodilatation in the golden hamster isolated mesenteric arterial bed. Br. J. Pharmacol. 117, 1797-1802
166. 2 receptors have salt-resistant hypertension and facilitated renal Na+ and water reabsorption. FASEB J. 21, 3717-3726
167. 2 receptor activation decreases blood pressure and increases renal Na(+) excretion. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R510-518
168. Rivest, S. (2009) Regulation of innate immune responses in the brain. Nat. Rev. Immunol. 9, 429-439
169. Roberts, S.B., Ripellino, J.A., Ingalls, K.M., Robakis, N.K. and Felsenstein, K.M. (1994) Non-amyloidogenic cleavage of the beta-amyloid precursor protein by an integral membrane metalloendopeptidase. J. Biol. Chem. 269, 3111-3116
170. 4 receptors in the rat hippocampus. J. Neurosci. 25, 6286-6295
171. Rodriguez-Zayas, A.E., Torrado, A.I. and Miranda, J.D. (2010) P2Y2 receptor expression is altered in rats after spinal cord injury. Int. J. Dev. Neurosci. 28, 413-421
172. Rothwell, N.J. and Luheshi, G.N. (2000) Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci. 23, 618-625
173. Rowe, W.B., Blalock, E.M., Chen, K.C., Kadish, I., Wang, D., Barrett, J.E., Thibault, O., Porter, N.M., Rose, G.M. and Landfield, P.W. (2007) Hippocampal expression analyses reveal selective association of immediate-early, neuroenergetic, and myelinogenic pathways with cognitive impairment in aged rats. J. Neurosci. 27, 3098-3110
174. Rozemuller, A.J., van Gool, W.A. and Eikelenboom, P. (2005) The neuroinflammatory response in plaques and amyloid angiopathy in Alzheimer's disease: therapeutic implications. Curr. Drug Targets CNS Neurol. Disord. 4, 223-233
175. 4 receptors in dorsal root, nodose and trigeminal ganglia of the rat. Histochem. Cell Biol. 120, 415-426
176. Ruitenberg, A., den Heijer, T., Bakker, S.L., van Swieten, J.C., Koudstaal, P.J., Hofman, A. and Breteler, M.M. (2005) Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam study. Ann. Neurol. 57, 789-794
177. Sagare, A.P., Bell, R.D. and Zlokovic, B.V. (2013) Neurovascular defects and faulty amyloid-beta vascular clearance in Alzheimer's disease. J. Alzheimers Dis. 33 (Suppl 1), S87-100
178. Sanada, M., Yasuda, H., Omatsu-Kanbe, M., Sango, K., Isono, T., Matsuura, H. and Kikkawa, R. (2002) Increase in intracellular Ca(2+) and calcitonin gene-related peptide release through metabotropic P2Y receptors in rat dorsal root ganglion neurons. Neuroscience 111, 413-422
179. Sanz, J.M., Chiozzi, P., Ferrari, D., Colaianna, M., Idzko, M., Falzoni, S., Fellin, R., Trabace, L. and Di Virgilio, F. (2009) Activation of microglia by amyloid {beta} requires P2X7 receptor expression. J. Immunol. 182, 4378-4385
180. Sasaki, Y., Hoshi, M., Akazawa, C., Nakamura, Y., Tsuzuki, H., Inoue, K. and Kohsaka, S. (2003). Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain. Glia 44, 242-250
181. Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Liao, Z., Lieberburg, I., Motter, R., Mutter, L., Soriano, F., Shopp, G., Vasquez, N., Vandevert, C., Walker, S., Wogulis, M., Yednock, T., Games, D., Seubert, P. (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400, 173-177
182. 2 nucleotide receptor up-regulation in submandibular gland cells from the NOD.B10 mouse model of Sjogren's syndrome. Arch. Oral Biol. 50, 533-540
183. Schuff, N., Matsumoto, S., Kmiecik, J., Studholme, C., Du, A., Ezekiel, F., Miller, B.L., Kramer, J.H., Jagust, W.J., Chui, H.C. and Weiner, M.W. (2009) Cerebral blood flow in ischemic vascular dementia and Alzheimer's disease, measured by arterial spin-labeling magnetic resonance imaging. Alzheimers Dement. 5, 454-462
184. Selkoe, D.J. (2001) Alzheimer's disease: genes, proteins, and therapy. Physiol. Rev. 81, 741-766
185. Serrano-Pozo, A., Frosch, M.P., Masliah E. and Hyman B.T. (2011) Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect. Med. 1, a006189
186. 2 nucleotide receptors mediate uridine 5′-triphosphate-induced intimal hyperplasia in collared rabbit carotid arteries. Circulation 106, 2720-2726
187. Shaftel, S.S., Carlson, T.J., Olschowka, J.A., Kyrkanides, S., Matousek, S.B. and O'Banion, M.K. (2007) Chronic interleukin-1beta expression in mouse brain leads to leukocyte infiltration and neutrophil-independent blood-brain barrier permeability without overt neurodegeneration. J. Neurosci. 27, 9301-9309
188. Shaftel, S.S., Griffin, W.S. and O'Banion, M.K. (2008) The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective. J. Neuroinflammation 5, 7
189. Shelat, P.B., Chalimoniuk, M., Wang, J.H., Strosznajder, J.B., Lee, J.C., Sun, A.Y., Simonyi, A. and Sun, G.Y. (2008) Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. J. Neurochem. 106, 45-55
190. 2 receptor in coronary artery smooth muscle cells. Mol. Pharmacol. 66, 1265-1274
191. Shie, F.S., Breyer, R.M. and Montine, T.J. (2005) Microglia lacking E Prostanoid Receptor subtype 2 have enhanced Abeta phagocytosis yet lack Abeta-activated neurotoxicity. Am. J. Pathol. 166, 1163-1172
192. Simard, A.R., Soulet, D., Gowing, G., Julien, J.P. and Rivest, S. (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 49, 489-502
193. Simon, J., Webb, T.E. and Barnard, E.A. (1997) Distribution of [35S]dATP alpha S binding sites in the adult rat neuraxis. Neuropharmacology 36, 1243-1251
194. Simonyi, A., He, Y., Sheng, W., Sun, A.Y., Wood, W.G., Weisman, G.A. and Sun, G.Y. (2010) Targeting NADPH oxidase and phospholipases A2 in Alzheimer's disease. Mol. Neurobiol. 41, 73-86
195. Sisodia, S.S. (1992) Beta-amyloid precursor protein cleavage by a membrane-bound protease. Proc. Natl. Acad. Sci. U.S.A. 89, 6075-6079
196. Skovronsky, D.M., Moore, D.B., Milla, M.E., Doms, R.W. and Lee, V.M. (2000) Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-golgi network. J. Biol. Chem. 275, 2568-2575
197. Sun, X., He, G., Qing, H., Zhou, W., Dobie, F., Cai, F., Staufenbiel, M., Huang, L.E. and Song, W. (2006) Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression. Proc. Natl. Acad. Sci. U.S.A. 103, 18727-18732
198. Suzuki, T., Hide, I., Ido, K., Kohsaka, S., Inoue, K. and Nakata, Y. (2004) Production and release of neuroprotective tumor necrosis factor by P2X7 receptor-activated microglia. J. Neurosci. 24, 1-7
199. Takenouchi, T., Iwamaru, Y., Sugama, S., Tsukimoto, M., Fujita, M., Sekigawa, A., Sekiyama, K., Sato, M., Kojima, S., Conti, B. (2011) The activation of P2X7 receptor induces cathepsin D-dependent production of a 20-kDa form of IL-1beta under acidic extracellular pH in LPS-primed microglial cells. J. Neurochem. 117, 712-723
200. Takenouchi, T., Sekiyama, K., Sekigawa, A., Fujita, M., Waragai, M., Sugama, S., Iwamaru, Y., Kitani, H. and Hashimoto, M. (2010) P2X7 receptor signaling pathway as a therapeutic target for neurodegenerative diseases. Arch. Immunol. Ther. Exp. (Warsz) 58, 91-96
201. Takenouchi, T., Sugama, S., Iwamaru, Y., Hashimoto, M. and Kitani, H. (2009) Modulation of the ATP-lnduced release and processing of IL-1beta in microglial cells. Crit. Rev. Immunol. 29, 335-345
202. Talamagas, A.A., Efthimiopoulos, S., Tsilibary, E.C., Figueiredo-Pereira, M.E. and Tzinia, A.K. (2007) Abeta(1-40)-induced secretion of matrix metalloproteinase-9 results in sAPPalpha release by association with cell surface APP. Neurobiol. Dis. 28, 304-315
203. Terada, H., Kajiura, T., Kyoi, K., Utsumi, S. and Hori, H. (1976) [Effects of ATP on cerebral circulation-morphological observation of cerebral circulation and cerebral vasculature]. No To Shinkei 28, 151-156
204. Toda, N., Kawakami, M., Yamazaki, M. and Okamura, T. (1991) Comparison of endothelium-dependent responses of monkey cerebral and temporal arteries. Br. J. Pharmacol. 102, 805-810
205. Tran, M.D. (2011) P2 receptor stimulation induces amyloid precursor protein production and secretion in rat cortical astrocytes. Neurosci. Lett. 492, 155-159
206. 2 nucleotide receptors in rat salivary gland cells during short-term culture. Am. J. Physiol. 273, C1100-1107
207. Uesugi, A., Kataoka, A., Tozaki-Saitoh, H., Koga, Y., Tsuda, M., Robaye, B., Boeynaems, J.M. and Inoue, K. (2012) Involvement of protein kinase D in uridine diphosphate-induced microglial macropinocytosis and phagocytosis. Glia 60, 1094-1105
208. Vassar, R., Kovacs, D.M., Yan, R. and Wong, P.C. (2009) The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential. J. Neurosci. 29, 12787-12794
209. 11 receptor. J. Immunol. 179, 8544-8553
210. Verkhratsky, A., Krishtal, O.A. and Burnstock, G. (2009) Purinoceptors on neuroglia. Mol. Neurobiol. 39, 190-208
211. Volonte, C., Amadio, S., D'Ambrosi, N., Colpi, M. and Burnstock, G. (2006) P2 receptor web: complexity and fine-tuning. Pharmacol. Ther. 112, 264-280
212. von Kugelgen, I., Spath, L. and Starke, K. (1994) Evidence for P2-purinoceptor-mediated inhibition of noradrenaline release in rat brain cortex. Br. J. Pharmacol. 113, 815-822
213. Walker, D.G., Kim, S.U. and McGeer, P.L. (1995) Complement and cytokine gene expression in cultured microglial derived from postmortem human brains. J. Neurosci. Res. 40, 478-493
214. 12 inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur. Heart J. 30, 1964-1977
215. 2 receptors mediate ATP-induced resensitization of TRPV1 expressed by kidney projecting sensory neurons. Am. J. Physiol Regul. Integr. Comp. Physiol. 298, R1634-1641
216. Warkentin, S., Ohlsson, M., Wollmer, P., Edenbrandt, L. and Minthon, L. (2004) Regional cerebral blood flow in Alzheimer's disease: classification and analysis of heterogeneity. Dement. Geriatr. Cogn. Disord. 17, 207-214
217. 2 receptor interactions in neuroinflammation. Mol. Neurobiol. 46, 96-113
218. Weisman, G.A., Woods, L.T., Erb, L. and Seye, C.I. (2012b) P2Y receptors in the mammalian nervous system: pharmacology, ligands and therapeutic potential. CNS Neurol. Disord. Drug Targets 11, 722-738
219. Westerman, M.A., Cooper-Blacketer, D., Mariash, A., Kotilinek, L., Kawarabayashi, T., Younkin, L.H., Carlson, G.A., Younkin, S.G. and Ashe, K.H. (2002) The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. J. Neurosci. 22, 1858-1867
220. Wihlborg, A.K., Malmsjo, M., Eyjolfsson, A., Gustafsson, R., Jacobson, K. and Erlinge, D. (2003) Extracellular nucleotides induce vasodilatation in human arteries via prostaglandins, nitric oxide and endothelium-derived hyperpolarising factor. Br. J. Pharmacol. 138, 1451-1458
221. 4 receptors and their sensitivity to extracellular H+ and Zn2+ ions. Br. J. Pharmacol. 140, 1177-1186
222. Wilkinson, B., Koenigsknecht-Talboo, J., Grommes, C., Lee, C.Y. and Landreth, G. (2006) Fibrillar beta-amyloid-stimulated intracellular signaling cascades require Vav for induction of respiratory burst and phagocytosis in monocytes and microglia. J. Biol. Chem. 281, 20842-20850
223. Wyss-Coray, T. and Rogers, J. (2012) Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb. Perspect. Med. 2:a006346
224. Xu, B., Stephens, A., Kirschenheuter, G., Greslin, A.F., Cheng, X., Sennelo, J., Cattaneo, M., Zighetti, M.L., Chen, A., Kim, S.A. (2002) Acyclic analogues of adenosine bisphosphates as P2Y receptor antagonists: phosphate substitution leads to multiple pathways of inhibition of platelet aggregation. J. Med. Chem. 45, 5694-5709
225. Yan, P., Hu, X., Song, H., Yin, K., Bateman, R.J., Cirrito, J.R., Xiao, Q., Hsu, F.F., Turk, J.W., Xu, J. (2006) Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. J. Biol. Chem. 281, 24566-24574
226. Yeh, W.L., Lu, D.Y., Lin, C.J., Liou, H.C. and Fu, W.M. (2007) Inhibition of hypoxia-induced increase of blood-brain barrier permeability by YC-1 through the antagonism of HIF-1alpha accumulation and VEGF expression. Mol. Pharmacol. 72, 440-449
227. Yu, W. and Hill, W.G. (2013) Lack of specificity shown by P2Y6 receptor antibodies. Naunyn Schmiedebergs Arch. Pharmacol. 386, 885-891
228. Zhang, X., Zhou, K., Wang, R., Cui, J., Lipton, S.A., Liao, F.F., Xu, H. and Zhang, Y.W. (2007) Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J. Biol. Chem. 282, 10873-10880
229. Zheng, Z., White, C., Lee, J., Peterson, T.S., Bush, A.I., Sun, G.Y., Weisman, G.A. and Petris, M.J. (2010) Altered microglial copper homeostasis in a mouse model of Alzheimer's disease. J. Neurochem. 114, 1630-1638
230. Zilka, N., Ferencik, M. and Hulin, I. (2006). Neuroinflammation in Alzheimer's disease: protector or promoter? Bratisl. Lek. Listy 107, 374-383
231. Zlokovic, B.V. (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57, 178-201