Celecoxib Inhibits Prion Protein 90-231-Mediated Pro-inflammatory Responses in Microglial Cells

Molecular Neurobiology

Volumn 53, Issue 1, 2016, Pages 57-72

  Villa, Valentina ^a   Thellung, Stefano ^a   Corsaro, Alessandro ^a   Novelli, Federica ^b   Tasso, Bruno ^b   Colucci D’Amato, Luca ^c   Gatta, Elena ^b   Tonelli, Michele ^b   Florio, Tullio ^a  

^a UNIVERSITY OF GENOA   (Italy)

^b UNIVERSITY OF GENOA   (Italy)

^c SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

Celecoxib; Cyclooxygenase; Microglia; Nitric oxide synthase; Prion diseases; PrP90 231

Indexed keywords

CELECOXIB; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; KETOPROFEN; NITRIC OXIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PRION PROTEIN; PROSTAGLANDIN E2; PRP 90 231 PROTEIN; UNCLASSIFIED DRUG; CONDITIONED MEDIUM; CYTOKINE; LIPOPOLYSACCHARIDE; PRION;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CELL ACTIVATION; CELL COUNTING; CELL MEDIATED CYTOTOXICITY; CELL PROLIFERATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; ENZYME ACTIVATION; INFLAMMATION; MICROGLIA; MTT ASSAY; NERVE DEGENERATION; NEUROTOXICITY; NONHUMAN; PEPTIDE SYNTHESIS; PRION DISEASE; PROSTAGLANDIN RELEASE; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; PROTEIN SYNTHESIS REGULATION; RAT; ANIMAL; CONDITIONED MEDIUM; DRUG EFFECTS; METABOLISM; NERVE CELL; PHARMACOLOGY; PRION; PRION DISEASES; SPRAGUE DAWLEY RAT;

ANIMALS; CELECOXIB; CULTURE MEDIA, CONDITIONED; CYTOKINES; LIPOPOLYSACCHARIDES; MICROGLIA; NEURONS; NITRIC OXIDE; PRION DISEASES; PRIONS; RATS, SPRAGUE-DAWLEY;

EID: 84953346308     PISSN: 08937648     EISSN: 15591182     Source Type: Journal    
DOI: 10.1007/s12035-014-8982-4     Document Type: Article

References (98)

1. Skaper SD (2007) The brain as a target for inflammatory processes and neuroprotective strategies. Ann N Y Acad Sci 1122:23–34
2. Prusiner SB (1998) Prions. Proc Natl Acad Sci U S A 95(23):13363–13383
3. Corsaro A, Thellung S, Villa V, Nizzari M, Florio T (2012) Role of prion protein aggregation in neurotoxicity. Int J Mol Sci 13(7):8648–8669
4. Prusiner SB (1998) The prion diseases. Brain Pathol 8(3):499–513
5. Muller WE, Ushijima H, Schroder HC, Forrest JM, Schatton WF, Rytik PG, Heffner-Lauc M (1993) Cytoprotective effect of NMDA receptor antagonists on prion protein (PrionSc)-induced toxicity in rat cortical cell cultures. Eur J Pharmacol 246(3):261–267
6. Sorrentino S, Bucciarelli T, Corsaro A, Tosatto A, Thellung S, Villa V, Schinina ME, Maras B, Galeno R, Scotti L, Creati F, Marrone A, Re N, Aceto A, Florio T, Mazzanti M (2012) Calcium binding promotes prion protein fragment 90–231 conformational change toward a membrane destabilizing and cytotoxic structure. PLoS One 7(7):e38314. doi:10.1371/journal.pone.0038314
7. Falsig J, Julius C, Margalith I, Schwarz P, Heppner FL, Aguzzi A (2008) A versatile prion replication assay in organotypic brain slices. Nat Neurosci 11(1):109–117
8. Mallucci G, Dickinson A, Linehan J, Klohn PC, Brandner S, Collinge J (2003) Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 302(5646):871–874
9. Pekny M, Nilsson M (2005) Astrocyte activation and reactive gliosis. Glia 50(4):427–434
10. Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C (2002) 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 202(1–2):13–23
11. Williams AE, Lawson LJ, Perry VH, Fraser H (1994) Characterization of the microglial response in murine scrapie. Neuropathol Appl Neurobiol 20(1):47–55
12. Tribouillard-Tanvier D, Race B, Striebel JF, Carroll JA, Phillips K, Chesebro B (2012) Early cytokine elevation, PrPres deposition and gliosis in mouse scrapie: no effect on disease by deletion of cytokine genes, IL-12p40 and IL-12p35. J Virol 86(19):10377-10383
13. Forloni G, Angeretti N, Chiesa R, Monzani E, Salmona M, Bugiani O, Tagliavini F (1993) Neurotoxicity of a prion protein fragment. Nature 362(6420):543–546
14. Brown DR (2000) Prion protein peptides: optimal toxicity and peptide blockade of toxicity. Mol Cell Neurosci 15(1):66–78
15. Thellung S, Florio T, Corsaro A, Arena S, Merlino M, Salmona M, Tagliavini F, Bugiani O, Forloni G, Schettini G (2000) Intracellular mechanisms mediating the neuronal death and astrogliosis induced by the prion protein fragment 106–126. Int J Dev Neurosci 18(4–5):481–492
16. Thellung S, Florio T, Villa V, Corsaro A, Arena S, Amico C, Robello M, Salmona M, Forloni G, Bugiani O, Tagliavini F, Schettini G (2000) Apoptotic cell death and impairment of L-type voltage-sensitive calcium channel activity in rat cerebellar granule cells treated with the prion protein fragment 106–126. Neurobiol Dis 7(4):299–309
17. Florio T, Paludi D, Villa V, Principe DR, Corsaro A, Millo E, Damonte G, D’Arrigo C, Russo C, Schettini G, Aceto A (2003) Contribution of two conserved glycine residues to fibrillogenesis of the 106–126 prion protein fragment. Evidence that a soluble variant of the 106–126 peptide is neurotoxic. J Neurochem 85(1):62–72
18. Florio T, Grimaldi M, Scorziello A, Salmona M, Bugiani O, Tagliavini F, Forloni G, Schettini G (1996) Intracellular calcium rise through L-type calcium channels, as molecular mechanism for prion protein fragment 106-126-induced astroglial proliferation. Biochem Biophys Res Commun 228(2):397–405
19. Mouillet-Richard S, Ermonval M, Chebassier C, Laplanche JL, Lehmann S, Launay JM, Kellermann O (2000) Signal transduction through prion protein. Science 289(5486):1925–1928
20. Brown DR, Schmidt B, Kretzschmar HA (1996) Role of microglia and host prion protein in neurotoxicity of a prion protein fragment. Nature 380(6572):345–347
21. Giese A, Brown DR, Groschup MH, Feldmann C, Haist I, Kretzschmar HA (1998) Role of microglia in neuronal cell death in prion disease. Brain Pathol 8(3):449–457
22. Corsaro A, Thellung S, Villa V, Nizzari M, Aceto A, Florio T (2012) Recombinant human prion protein fragment 90–231, a useful model to study prion neurotoxicity. Omics: J Integ Biol 16(1–2):50–59. doi:10.1089/omi.2011.0038
23. Corsaro A, Thellung S, Russo C, Villa V, Arena S, D’Adamo MC, Paludi D, Rossi Principe D, Damonte G, Benatti U, Aceto A, Tagliavini F, Schettini G, Florio T (2002) Expression in E. coli and purification of recombinant fragments of wild type and mutant human prion protein. Neurochem Int 41(1):55–63
24. Checler F, Vincent B (2002) Alzheimer’s and prion diseases: distinct pathologies, common proteolytic denominators. Trends Neurosci 25(12):616–620
25. Chen SG, Teplow DB, Parchi P, Teller JK, Gambetti P, Autilio-Gambetti L (1995) Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem 270(32):19173–19180
26. Zou WQ, Capellari S, Parchi P, Sy MS, Gambetti P, Chen SG (2003) Identification of novel proteinase K-resistant C-terminal fragments of PrP in Creutzfeldt-Jakob disease. J Biol Chem 278(42):40429–40436
27. Chiesa R, Harris DA (2001) Prion diseases: what is the neurotoxic molecule? Neurobiol Dis 8(5):743–763
28. Corsaro A, Paludi D, Villa V, D’Arrigo C, Chiovitti K, Thellung S, Russo C, Di Cola D, Ballerini P, Patrone E, Schettini G, Aceto A, Florio T (2006) Conformation dependent pro-apoptotic activity of the recombinant human prion protein fragment 90–231. Int J Immunopathol Pharmacol 19(2):339–356
29. Villa V, Corsaro A, Thellung S, Paludi D, Chiovitti K, Venezia V, Nizzari M, Russo C, Schettini G, Aceto A, Florio T (2006) Characterization of the proapoptotic intracellular mechanisms induced by a toxic conformer of the recombinant human prion protein fragment 90–231. Ann N Y Acad Sci 1090:276–291
30. Chiovitti K, Corsaro A, Thellung S, Villa V, Paludi D, D’Arrigo C, Russo C, Perico A, Ianieri A, Di Cola D, Vergara A, Aceto A, Florio T (2007) Intracellular accumulation of a mild-denatured monomer of the human PrP fragment 90–231, as possible mechanism of its neurotoxic effects. J Neurochem 103(6):2597–2609
31. Corsaro A, Thellung S, Chiovitti K, Villa V, Simi A, Raggi F, Paludi D, Russo C, Aceto A, Florio T (2009) Dual modulation of ERK1/2 and p38 MAP kinase activities induced by minocycline reverses the neurotoxic effects of the prion protein fragment 90–231. Neurotox Res 15(2):138–154
32. Thellung S, Corsaro A, Villa V, Simi A, Vella S, Pagano A, Florio T (2011) Human PrP90-231-induced cell death is associated with intracellular accumulation of insoluble and protease-resistant macroaggregates and lysosomal dysfunction. Cell Death Disease 2:e138
33. Thellung S, Gatta E, Pellistri F, Corsaro A, Villa V, Vassalli M, Robello M, Florio T (2013) Excitotoxicity through NMDA receptors mediates cerebellar granule neuron apoptosis induced by prion protein 90–231 fragment. Neurotox Res 23(4):301–314
34. Villa V, Tonelli M, Thellung S, Corsaro A, Tasso B, Novelli F, Canu C, Pino A, Chiovitti K, Paludi D, Russo C, Sparatore A, Aceto A, Boido V, Sparatore F, Florio T (2011) Efficacy of novel acridine derivatives in the inhibition of hPrP90-231 prion protein fragment toxicity. Neurotox Res 19(4):556–574
35. Corsaro A, Thellung S, Bucciarelli T, Scotti L, Chiovitti K, Villa V, D’Arrigo C, Aceto A, Florio T (2011) High hydrophobic amino acid exposure is responsible of the neurotoxic effects induced by E200K or D202N disease-related mutations of the human prion protein. Int J Biochem Cell Biol 43(3):372–382. doi:10.1016/j.biocel.2010.11.007
36. Paulis D, Maras B, Schinina ME, di Francesco L, Principe S, Galeno R, Abdel-Haq H, Cardone F, Florio T, Pocchiari M, Mazzanti M (2011) The pathological prion protein forms ionic conductance in lipid bilayer. Neurochem Int 59(2):168–174
37. Thellung S, Villa V, Corsaro A, Pellistri F, Venezia V, Russo C, Aceto A, Robello M, Florio T (2007) ERK1/2 and p38 MAP kinases control prion protein fragment 90-231-induced astrocyte proliferation and microglia activation. Glia 55(14):1469–1485
38. Thellung S, Corsaro A, Villa V, Venezia V, Nizzari M, Bisaglia M, Russo C, Schettini G, Aceto A, Florio T (2007) Amino-terminally truncated prion protein PrP90-231 induces microglial activation in vitro. Ann N Y Acad Sci 1096:258–270
39. Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10(11):1387–1394
40. Gao HM, Hong JS (2008) Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol 29(8):357–365
41. Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8(1):57–69
42. Perry VH, Cunningham C, Boche D (2002) Atypical inflammation in the central nervous system in prion disease. Curr Opin Neurol 15(3):349–354
43. Marella M, Gaggioli C, Batoz M, Deckert M, Tartare-Deckert S, Chabry J (2005) Pathological prion protein exposure switches on neuronal mitogen-activated protein kinase pathway resulting in microglia recruitment. J Biol Chem 280(2):1529–1534
44. Eikelenboom P, Bate C, Van Gool WA, Hoozemans JJ, Rozemuller JM, Veerhuis R, Williams A (2002) Neuroinflammation in Alzheimer’s disease and prion disease. Glia 40(2):232–239
45. Int’ Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, Breteler MM, Stricker BH (2001) Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med 345(21):1515–1521
46. Aguzzi A, Heikenwalder M, Miele G (2004) Progress and problems in the biology, diagnostics, and therapeutics of prion diseases. J Clin Invest 114(2):153–160
47. Forloni G, Iussich S, Awan T, Colombo L, Angeretti N, Girola L, Bertani I, Poli G, Caramelli M, Grazia Bruzzone M, Farina L, Limido L, Rossi G, Giaccone G, Ironside JW, Bugiani O, Salmona M, Tagliavini F (2002) Tetracyclines affect prion infectivity. Proc Natl Acad Sci U S A 99(16):10849–10854
48. Collinge J, Gorham M, Hudson F, Kennedy A, Keogh G, Pal S, Rossor M, Rudge P, Siddique D, Spyer M, Thomas D, Walker S, Webb T, Wroe S, Darbyshire J (2009) Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial. Lancet Neurol 8(4):334–344
49. Ciccarelli R, Di Iorio P, D’Alimonte I, Giuliani P, Florio T, Caciagli F, Middlemiss PJ, Rathbone MP (2000) Cultured astrocyte proliferation induced by extracellular guanosine involves endogenous adenosine and is raised by the co-presence of microglia. Glia 29(3):202–211
50. Colucci-D’Amato GL, Tino A, Pernas-Alonso R, ffrench-Mullen JM, di Porzio U (1999) Neuronal and glial properties coexist in a novel mouse CNS immortalized cell line. Exp Cell Res 252(2):383–391
51. Chambery A, Colucci-D’Amato L, Vissers JP, Scarpella S, Langridge JI, Parente A (2009) Proteomic profiling of proliferating and differentiated neural mes-c-myc A1 cell line from mouse embryonic mesencephalon by LC-MS. J Proteome Res 8(1):227–238. doi:10.1021/pr800454n
52. Gentile MT, Nawa Y, Lunardi G, Florio T, Matsui H, Colucci-D’Amato L (2012) Tryptophan hydroxylase 2 (TPH2) in a neuronal cell line: modulation by cell differentiation and NRSF/rest activity. J Neurochem 123(6):963–970
53. Paludi D, Thellung S, Chiovitti K, Corsaro A, Villa V, Russo C, Ianieri A, Bertsch U, Kretzschmar HA, Aceto A, Florio T (2007) Different structural stability and toxicity of PrP(ARR) and PrP(ARQ) sheep prion protein variants. J Neurochem 103(6):2291–2300
54. Jones LJ, Gray M, Yue ST, Haugland RP, Singer VL (2001) Sensitive determination of cell number using the CyQUANT cell proliferation assay. J Immunol Methods 254(1–2):85–98
55. Baker BJ, Park KW, Qin H, Ma X, Benveniste EN (2010) IL-27 inhibits OSM-mediated TNF-alpha and iNOS gene expression in microglia. Glia 58(9):1082–1093
56. Arena S, Pattarozzi A, Corsaro A, Schettini G, Florio T (2005) Somatostatin receptor subtype-dependent regulation of nitric oxide release: involvement of different intracellular pathways. Mol Endocrinol 19(1):255–267
57. Thellung S, Villa V, Corsaro A, Arena S, Millo E, Damonte G, Benatti U, Tagliavini F, Florio T, Schettini G (2002) p38 MAP kinase mediates the cell death induced by PrP106-126 in the SH-SY5Y neuroblastoma cells. Neurobiol Dis 9(1):69–81
58. Bruce-Keller AJ, Keeling JL, Keller JN, Huang FF, Camondola S, Mattson MP (2000) Antiinflammatory effects of estrogen on microglial activation. Endocrinology 141(10):3646–3656
59. Bonaiuto C, McDonald PP, Rossi F, Cassatella MA (1997) Activation of nuclear factor-kappa B by beta-amyloid peptides and interferon-gamma in murine microglia. J Neuroimmunol 77(1):51–56
60. Tiffany HL, Lavigne MC, Cui YH, Wang JM, Leto TL, Gao JL, Murphy PM (2001) Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide receptor 2, a G protein-coupled receptor expressed in phagocytes and brain. J Biol Chem 276(26):23645–23652
61. Chen K, Iribarren P, Hu J, Chen J, Gong W, Cho EH, Lockett S, Dunlop NM, Wang JM (2006) Activation of Toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid beta peptide. J Biol Chem 281(6):3651–3659
62. Weidner AM, Housley M, Murphy MP, Levine H 3rd (2011) Purified high molecular weight synthetic Abeta(1–42) and biological Abeta oligomers are equipotent in rapidly inducing MTT formazan exocytosis. Neurosci Lett 497(1):1–5
63. Minghetti L, Pocchiari M (2007) Cyclooxygenase-2, prostaglandin E2, and microglial activation in prion diseases. Int Rev Neurobiol 82:265–275
64. Rozemuller AJ, Jansen C, Carrano A, van Haastert ES, Hondius D, van der Vies SM, Hoozemans JJ (2012) Neuroinflammation and common mechanism in Alzheimer’s disease and prion amyloidosis: amyloid-associated proteins, neuroinflammation and neurofibrillary degeneration. Neurodegener Dis 10(1–4):301–304
65. Guiroy DC, Wakayama I, Liberski PP, Gajdusek DC (1994) Relationship of microglia and scrapie amyloid-immunoreactive plaques in kuru, Creutzfeldt-Jakob disease and Gerstmann-Straussler syndrome. Acta Neuropathol 87(5):526–530
66. Williams AE, van Dam AM, Man AHWK, Berkenbosch F, Eikelenboom P, Fraser H (1994) Cytokines, prostaglandins and lipocortin-1 are present in the brains of scrapie-infected mice. Brain Res 654(2):200–206
67. Brown DR, Schmidt B, Kretzschmar HA (1996) A neurotoxic prion protein fragment enhances proliferation of microglia but not astrocytes in culture. Glia 18(1):59–67
68. Qiu WQ, Ye Z, Kholodenko D, Seubert P, Selkoe DJ (1997) Degradation of amyloid beta-protein by a metalloprotease secreted by microglia and other neural and non-neural cells. J Biol Chem 272(10):6641–6646
69. Paresce DM, Ghosh RN, Maxfield FR (1996) Microglial cells internalize aggregates of the Alzheimer’s disease amyloid beta-protein via a scavenger receptor. Neuron 17(3):553–565
70. Kranich J, Krautler NJ, Falsig J, Ballmer B, Li S, Hutter G, Schwarz P, Moos R, Julius C, Miele G, Aguzzi A (2010) Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain-dependent manner. J Exp Med 207(10):2271–2281
71. Freixes M, Rodriguez A, Dalfo E, Ferrer I (2006) Oxidation, glycoxidation, lipoxidation, nitration, and responses to oxidative stress in the cerebral cortex in Creutzfeldt-Jakob disease. Neurobiol Aging 27(12):1807–1815
72. Kim JI, Ju WK, Choi JH, Choi E, Carp RI, Wisniewski HM, Kim YS (1999) Expression of cytokine genes and increased nuclear factor-kappa B activity in the brains of scrapie-infected mice. Brain Res Mol Brain Res 73(1–2):17–27
73. Muhleisen H, Gehrmann J, Meyermann R (1995) Reactive microglia in Creutzfeldt-Jakob disease. Neuropathol Appl Neurobiol 21(6):505–517
74. Lleo A, Galea E, Sastre M (2007) Molecular targets of non-steroidal anti-inflammatory drugs in neurodegenerative diseases. Cell Mol Life Sci 64(11):1403–1418
75. Imbimbo BP, Solfrizzi V, Panza F (2010) Are NSAIDs useful to treat Alzheimer’s disease or mild cognitive impairment? Front Aging Neurosci 2
76. Forloni G, Artuso V, Roiter I, Morbin M, Tagliavini F (2013) Therapy in prion diseases. Curr Top Med Chem 13(19):2465–2476
77. Farooqui AA, Ong WY, Horrocks LA (2006) Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev 58(3):591–620
78. Brown DR, Herms JW, Schmidt B, Kretzschmar HA (1997) PrP and beta-amyloid fragments activate different neurotoxic mechanisms in cultured mouse cells. Eur J Neurosci 9(6):1162–1169
79. Combs CK, Johnson DE, Cannady SB, Lehman TM, Landreth GE (1999) Identification of microglial signal transduction pathways mediating a neurotoxic response to amyloidogenic fragments of beta-amyloid and prion proteins. J Neurosci 19(3):928–939
80. Fabrizi C, Silei V, Menegazzi M, Salmona M, Bugiani O, Tagliavini F, Suzuki H, Lauro GM (2001) The stimulation of inducible nitric-oxide synthase by the prion protein fragment 106–126 in human microglia is tumor necrosis factor-alpha-dependent and involves p38 mitogen-activated protein kinase. J Biol Chem 276(28):25692–25696
81. Bate C, Boshuizen RS, Langeveld JP, Williams A (2002) Temporal and spatial relationship between the death of PrP-damaged neurones and microglial activation. Neuroreport 13(13):1695–1700
82. Gibbons HM, Dragunow M (2006) Microglia induce neural cell death via a proximity-dependent mechanism involving nitric oxide. Brain Res 1084(1):1–15
83. Bate C, Kempster S, Williams A (2006) Prostaglandin D2 mediates neuronal damage by amyloid-beta or prions which activates microglial cells. Neuropharmacology 50(2):229–237
84. Iravani MM, Kashefi K, Mander P, Rose S, Jenner P (2002) Involvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegeneration. Neuroscience 110(1):49–58
85. He Y, Imam SZ, Dong Z, Jankovic J, Ali SF, Appel SH, Le W (2003) Role of nitric oxide in rotenone-induced nigro-striatal injury. J Neurochem 86(6):1338–1345
86. Lee P, Son D, Lee J, Kim YS, Kim H, Kim SY (2003) Excessive production of nitric oxide induces the neuronal cell death in lipopolysaccharide-treated rat hippocampal slice culture. Neurosci Lett 349(1):33–36
87. Schutze S, Loleit T, Zeretzke M, Bunkowski S, Bruck W, Ribes S, Nau R (2012) Additive microglia-mediated neuronal injury caused by amyloid-beta and bacterial TLR agonists in murine neuron-microglia co-cultures quantified by an automated image analysis using cognition network technology. J Alzheimers Dis 31(3):651–657
88. Skaper SD, Facci L, Giusti P (2013) Intracellular ion channel CLIC1: involvement in microglia-mediated beta-amyloid peptide(1–42) neurotoxicity. Neurochem Res 38(9):1801–1808
89. Riemer C, Gultner S, Heise I, Holtkamp N, Baier M (2009) Neuroinflammation in prion diseases: concepts and targets for therapeutic intervention. CNS Neurol Disord Drug Targets 8(5):329–341
90. Hochstrasser T, Hohsfield LA, Sperner-Unterweger B, Humpel C (2013) beta-Amyloid induced effects on cholinergic, serotonergic, and dopaminergic neurons is differentially counteracted by anti-inflammatory drugs. J Neurosci Res 91(1):83–94
91. White MC, Johnson GG, Zhang W, Hobrath JV, Piazza GA, Grimaldi M (2013) Sulindac sulfide inhibits sarcoendoplasmic reticulum Ca2+ ATPase, induces endoplasmic reticulum stress response, and exerts toxicity in glioma cells: relevant similarities to and important differences from celecoxib. J Neurosci Res 91(3):393–406. doi:10.1002/jnr.23169
92. Johnson GG, White MC, Wu JH, Vallejo M, Grimaldi M (2014) The deadly connection between endoplasmic reticulum, Ca2+, protein synthesis, and the endoplasmic reticulum stress response in malignant glioma cells. Neuro-Oncology 16(8):1086–1099
93. Swierkosz TA, Mitchell JA, Warner TD, Botting RM, Vane JR (1995) Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids. Br J Pharmacol 114(7):1335–1342
94. Salvemini D, Manning PT, Zweifel BS, Seibert K, Connor J, Currie MG, Needleman P, Masferrer JL (1995) Dual inhibition of nitric oxide and prostaglandin production contributes to the antiinflammatory properties of nitric oxide synthase inhibitors. J Clin Invest 96(1):301–308
95. Hamilton LC, Warner TD (1998) Interactions between inducible isoforms of nitric oxide synthase and cyclo-oxygenase in vivo: investigations using the selective inhibitors, 1400W and celecoxib. Br J Pharmacol 125(2):335–340
96. Huang Y, Liu J, Wang LZ, Zhang WY, Zhu XZ (2005) Neuroprotective effects of cyclooxygenase-2 inhibitor celecoxib against toxicity of LPS-stimulated macrophages toward motor neurons. Acta Pharmacol Sin 26(8):952–958
97. Chiang YM, Lo CP, Chen YP, Wang SY, Yang NS, Kuo YH, Shyur LF (2005) Ethyl caffeate suppresses NF-kappaB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE2 in vitro or in mouse skin. Br J Pharmacol 146(3):352–363
98. Choi Y, Lee MK, Lim SY, Sung SH, Kim YC (2009) Inhibition of inducible NO synthase, cyclooxygenase-2 and interleukin-1beta by torilin is mediated by mitogen-activated protein kinases in microglial BV2 cells. Br J Pharmacol 156(6):933–940