NO-flurbiprofen reduces amyloid-β, is neuroprotective in cell culture, and enhances cognition in response to cholinergic blockade

Journal of Neurochemistry

Volumn 111, Issue 3, 2009, Pages 766-776

  Abdul Hay, Samer O ^a   Luo, Jia ^a   Ashghodom, Rezene T ^a   Thatcher, Gregory R J ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

Alzheimer's disease; Amyloid; Nitrate; Non steroidal anti inflammatory drug

Indexed keywords

AMINO ACID; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-42]; CYCLIC GMP; FLURBIPROFEN; FLURBIPROFEN 4 NITROXYBUTYL ESTER; NITRATE; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN SYNTHASE; SCOPOLAMINE;

AMINO ACID BLOOD LEVEL; ANIMAL CELL; ANIMAL EXPERIMENT; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BEHAVIOR; CELL ASSAY; CELL CULTURE; CHOLINERGIC RECEPTOR BLOCKING; COGNITION; COGNITIVE DEFECT; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFICACY; DRUG INHIBITION; DRUG POTENCY; DRUG TARGETING; IN VITRO STUDY; IN VIVO STUDY; MALE; MEMORY; MOUSE; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; REFERENCE MEMORY; SIGNAL TRANSDUCTION; SPATIAL MEMORY;

AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; AVOIDANCE LEARNING; CELL LINE, TUMOR; COGNITION DISORDERS; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME-LINKED IMMUNOSORBENT ASSAY; FLURBIPROFEN; HUMANS; IMMUNOPRECIPITATION; LIPOPOLYSACCHARIDES; MALE; MAZE LEARNING; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NEUROBLASTOMA; NEUROPROTECTIVE AGENTS; NITRIC OXIDE SYNTHASE TYPE II; PEPTIDE FRAGMENTS; PROSTAGLANDINS; RATS; RATS, LONG-EVANS; SCOPOLAMINE; SPECTROMETRY, MASS, MATRIX-ASSISTED LASER DESORPTION-IONIZATION; TETRAZOLIUM SALTS; THIAZOLES; TRANSFECTION;

EID: 70349915914     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/j.1471-4159.2009.06353.x     Document Type: Article

References (73)

1. Abdul-Hay S. O., Edirisinghe P. Thatcher G. R. J. (2009) Selective modulation of amyloid β peptide degradation by flurbiprofen, fenofibrate, and related compounds regulates Aβ levels. J. Neurochem. doi
2. Ajmone-Cat M. A., Nicolini A. Minghetti L. (2001) Differential effects of the nonsteroidal antiinflammatory drug flurbiprofen and its nitric oxide-releasing derivative, nitroflurbiprofen, on prostaglandin E(2), interleukin-1beta, and nitric oxide synthesis by activated microglia. J. Neurosci. Res. 66, 715 722.
3. Akiyama H., Barger S., Barnum S. et al. (2000) Inflammation and Alzheimer's disease. Neurobiol. Aging 21, 383 421.
4. Bartus R. T., Dean R. L. III., Beer B. Lippa A. S. (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217, 408 414.
5. Bennett B. M., Reynolds J. N., Prusky G. T., Douglas R. M., Sutherland R. J. Thatcher G. R. (2007) Cognitive deficits in rats after forebrain cholinergic depletion are reversed by a novel NO mimetic nitrate ester. Neuropsychopharmacology 32, 505 513.
6. Bernardo A., Gasparini L., Ongini E. Minghetti L. (2006) Dynamic regulation of microglial functions by the non-steroidal anti-inflammatory drug NCX 2216: implications for chronic treatments of neurodegenerative diseases. Neurobiol. Dis. 22, 25 32.
7. Bhat N. R., Feinstein D. L., Shen Q. Bhat A. N. (2002) p38 MAPK-mediated transcriptional activation of inducible nitric-oxide synthase in glial cells. Roles of nuclear factors, nuclear factor kappa B, cAMP response element-binding protein CCAAT/enhancer-binding protein-beta, and activating transcription factor-2. J. Biol. Chem. 277, 29584 29592.
8. Bolla M., Almirante N. Benedini F. (2005) Therapeutic potential of nitrate esters of commonly used drugs. Curr. Top. Med. Chem. 5, 707 720.
9. Bonkale W. L., Winblad B., Ravid R. Cowburn R. F. (1995) Reduced nitric oxide responsive soluble guanylyl cyclase activity in the superior temporal cortex of patients with Alzheimer's disease. Neurosci. Lett. 187, 5 8.
10. Bredt D. S. Snyder S. H. (1989) Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc. Natl Acad. Sci. USA 86, 9030 9033.
11. Breitner J. C., Haneuse S. J., Walker R., Dublin S., Crane P. K., Gray S. L. Larson E. B. (2009) Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort. Neurology 72, 1899 1905.
12. Butterfield D. A., Griffin S., Munch G. Pasinetti G. M. (2002) Amyloid beta-peptide and amyloid pathology are central to the oxidative stress and inflammatory cascades under which Alzheimer's disease brain exists. J. Alzheimers Dis. 4, 193 201.
13. Chalmers I. M., Cathcart B. J., Kumar E. B., Dick W. C. Buchanan W. W. (1972) Clinico-pharmacological studies and clinical evaluation of flurbiprofen. A new non-steroidal antirheumatic agent. Ann. Rheum. Dis. 31, 319 324.
14. Cullen W. K., Suh Y. H., Anwyl R. Rowan M. J. (1997) Block of LTP in rat hippocampus in vivo by beta-amyloid precursor protein fragments. Neuroreport 8, 3213 3217.
15. Devan B. D., Sierra-Mercado D. Jr., Jimenez M., Bowker J. L., Duffy K. B., Spangler E. L. Ingram D. K. (2004) Phosphodiesterase inhibition by sildenafil citrate attenuates the learning impairment induced by blockade of cholinergic muscarinic receptors in rats. Pharmacol. Biochem. Behav. 79, 691 699.
16. Devan B. D., Bowker J. L., Duffy K. B., Bharati I. S., Jimenez M., Sierra-Mercado D. Jr., Nelson C. M., Spangler E. L. Ingram D. K. (2006) Phosphodiesterase inhibition by sildenafil citrate attenuates a maze learning impairment in rats induced by nitric oxide synthase inhibition. Psychopharmacology (Berl.) 183, 439 445.
17. Eriksen J. L., Sagi S. A., Smith T. E. et al. (2003) NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J. Clin. Invest. 112, 440 449.
18. Francis P. T., Palmer A. M., Snape M. Wilcock G. K. (1999) The cholinergic hypothesis of Alzheimer's disease: a review of progress. J. Neurol. Neurosurg. Psychiatry 66, 137 147.
19. Furlan R., Kurne A., Bergami A. et al. (2004) A nitric oxide releasing derivative of flurbiprofen inhibits experimental autoimmune encephalomyelitis. J. Neuroimmunol. 150, 10 19.
20. Galasko D. R., Graff-Radford N., May S. et al. (2007) Safety, tolerability, pharmacokinetics, and Abeta levels after short-term administration of R-flurbiprofen in healthy elderly individuals. Alzheimer Dis. Assoc. Disord. 21, 292 299.
21. Garthwaite J., Garthwaite G., Palmer R. M. Moncada S. (1989) NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices. Eur. J. Pharmacol. 172, 413 416.
22. Gasparini L., Ongini E. Wenk G. (2004) Non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease: old and new mechanisms of action. J. Neurochem. 91, 521 536.
23. Gasparini L., Ongini E., Wilcock D. Morgan D. (2005) Activity of flurbiprofen and chemically related anti-inflammatory drugs in models of Alzheimer's disease. Brain Res. Brain Res. Rev. 48, 400 408.
24. Govoni M., Casagrande S., Maucci R., Chiroli V. Tocchetti P. (2006) In vitro metabolism of (nitrooxy)butyl ester nitric oxide-releasing compounds: comparison with glyceryl trinitrate. J. Pharmacol. Exp. Ther. 317, 752 761.
25. van Groen T. Kadish I. (2005) Transgenic AD model mice, effects of potential anti-AD treatments on inflammation and pathology. Brain Res. Brain Res. Rev. 48, 370 378.
26. Hagos G. K., Abdul-Hay S. O., Sohn J., Edirisinghe P. D., Chandrasena R. E., Wang Z., Li Q. Thatcher G. R. (2008) Anti-inflammatory, antiproliferative, and cytoprotective activity of NO chimera nitrates of use in cancer chemoprevention. Mol. Pharmacol. 74, 1381 1391.
27. Hardy J. Selkoe D. J. (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science (USA) 297, 353 356.
28. Hauss-Wegrzyniak B., Vraniak P. Wenk G. L. (1999a) The effects of a novel NSAID on chronic neuroinflammation are age dependent. Neurobiol. Aging 20, 305 313.
29. Hauss-Wegrzyniak B., Willard L. B., Del Soldato P., Pepeu G. Wenk G. L. (1999b) Peripheral administration of novel anti-inflammatories can attenuate the effects of chronic inflammation within the CNS. Brain Res. 815, 36 43.
30. Hinz B., Brune K., Rau T. Pahl A. (2001) Flurbiprofen enantiomers inhibit inducible nitric oxide synthase expression in RAW 264.7 macrophages. Pharm. Res. 18, 151 156.
31. Idris A. I., Ralston S. H. van't Hof R. J. (2009) The nitrosylated flurbiprofen derivative HCT1026 inhibits cytokine-induced signalling through a novel mechanism of action. Eur. J. Pharmacol. 602, 215 222.
32. Ingram D. K., Spangler E. L., Meyer R. C. London E. D. (1998) Learning in a 14-unit T-maze is impaired in rats following systemic treatment with N omega-nitro-L-arginine. Eur. J. Pharmacol. 341, 1 9.
33. Jantzen P. T., Connor K. E., DiCarlo G., Wenk G. L., Wallace J. L., Rojiani A. M., Coppola D., Morgan D. Gordon M. N. (2002) Microglial activation and beta -amyloid deposit reduction caused by a nitric oxide-releasing nonsteroidal anti-inflammatory drug in amyloid precursor protein plus presenilin-1 transgenic mice. J. Neurosci. 22, 2246 2254.
34. Kim J., Onstead L., Randle S., Price R., Smithson L., Zwizinski C., Dickson D. W., Golde T. McGowan E. (2007) Abeta40 inhibits amyloid deposition in vivo. J. Neurosci. 27, 627 633.
35. Klegeris A. McGeer P. L. (2002) Cyclooxygenase and 5-lipoxygenase inhibitors protect against mononuclear phagocyte neurotoxicity. Neurobiol. Aging 23, 787 794.
36. Kowalska M. A. Badellino K. (1994) beta-Amyloid protein induces platelet aggregation and supports platelet adhesion. Biochem. Biophys. Res. Commun. 205, 1829 1835.
37. Lundberg J. O., Weitzberg E. Gladwin M. T. (2008) The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat. Rev. Drug Discov. 7, 156 167.
38. MacNaughton W. K., Cirino G. Wallace J. L. (1989) Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach. Life Sci. 45, 1869 1876.
39. Mariotto S., Menegazzi M., Carcereri de Prati A., Cuzzolin L., Adami A., Suzuki H. Benoni G. (1995) Protective effect of NO on gastric lesions and inhibition of expression of gastric inducible NOS by flurbiprofen and its nitro-derivative, nitroflurbiprofen. Br. J. Pharmacol. 116, 1713 1714.
40. Masliah E. (1995) Mechanisms of synaptic dysfunction in Alzheimer's disease. Histol. Histopathol. 10, 509 519.
41. Mattson M. P., Guo Z. H. Geiger J. D. (1999) Secreted form of amyloid precursor protein enhances basal glucose and glutamate transport and protects against oxidative impairment of glucose and glutamate transport in synaptosomes by a cyclic GMP- mediated mechanism. J. Neurochem. 73, 532 537.
42. Morihara T., Chu T., Ubeda O., Beech W. Cole G. M. (2002) Selective inhibition of Abeta42 production by NSAID R-enantiomers. J. Neurochem. 83, 1009 1012.
43. O'Dell T. J., Hawkins R. D., Kandel E. R. Arancio O. (1991) Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proc. Natl Acad. Sci. USA 88, 11285 11289.
44. Prosperi C., Scali C., Pepeu G. Casamenti F. (2001) NO-flurbiprofen attenuates excitotoxin-induced brain inflammation, and releases nitric oxide in the brain. Jpn. J. Pharmacol. 86, 230 235.
45. Prosperi C., Scali C., Barba M., Bellucci A., Giovannini M. G., Pepeu G. Casamenti F. (2004) Comparison between flurbiprofen and its nitric oxide-releasing derivatives HCT-1026 and NCX-2216 on Abeta(1-42)-induced brain inflammation and neuronal damage in the rat. Int. J. Immunopathol. Pharmacol. 17, 317 330.
46. Puzzo D., Vitolo O., Trinchese F., Jacob J. P., Palmeri A. Arancio O. (2005) Amyloid-beta peptide inhibits activation of the nitric oxide/cGMP/cAMP-responsive element-binding protein pathway during hippocampal synaptic plasticity. J. Neurosci. 25, 6887 6897.
47. Rich J. B., Rasmusson D. X., Folstein M. F., Carson K. A., Kawas C. Brandt J. (1995) Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology 45, 51 55.
48. Ronchetti D., Impagnatiello F., Guzzetta M., Gasparini L., Borgatti M., Gambari R. Ongini E. (2006) Modulation of iNOS expression by a nitric oxide-releasing derivative of the natural antioxidant ferulic acid in activated RAW 264.7 macrophages. Eur. J. Pharmacol. 532, 162 169.
49. Rosi S., McGann K., Hauss-Wegrzyniak B. Wenk G. L. (2003) The influence of brain inflammation upon neuronal adenosine A2B receptors. J. Neurochem. 86, 220 227.
50. Schenk D., Barbour R., Dunn W. et al. (1999) Immunization with amyloid-b attenuates Alzheimer's disease-like pathology in the PDAPP mouse. Nature (London) 400, 173 177.
51. Smith S., Dringenberg H. C., Bennett B. M., Thatcher G. R. J. Reynolds J. N. (2000) A novel nitrate ester reverses the cognitive impairment caused by scopolamine in the Morris water maze. Neuroreport 11, 3883 3886.
52. Somasundaram S., Rafi S., Jacob M. et al. (1997) Intestinal tolerability of nitroxybutyl-flurbiprofen in rats. Gut 40, 608 613.
53. Stewart W. F., Kawas C., Corrada M. Metter E. J. (1997) Risk of Alzheimer's disease and duration of NSAID use. Neurology 48, 626 632.
54. Szekely C. A., Green R. C., Breitner J. C. et al. (2008) No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer's dementia in six pooled cohort studies. Neurology 70, 2291 2298.
55. Terry A. V. Jr. Buccafusco J. J. (2003) The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J. Pharmacol. Exp. Ther. 306, 821 827.
56. Thatcher G. R. J., Bennett B. M., Dringenberg H. C. Reynolds J. N. (2004) Novel nitrates as NO mimetics directed at Alzheimer's disease. J. Alzheimers Dis. 6, S75 S84.
57. Thatcher G. R. J., Bennett B. M. Reynolds J. N. (2005) Nitric oxide mimetic molecules as therapeutic agents in Alzheimer's disease. Curr. Alzheimer Res. 2, 171 182.
58. Thatcher G. R. J., Bennett B. M. Reynolds J. N. (2006) NO chimeras as therapeutic agents in Alzheimer's disease. Curr. Alzheimer Res. 3, 237 245.
59. Thomas E., Snyder P. J., Pietrzak R. H., Jackson C. E., Bednar M. Maruff P. (2008) Specific impairments in visuospatial working and short-term memory following low-dose scopolamine challenge in healthy older adults. Neuropsychologia 46, 2476 2484.
60. Ting K. K., Brew B. Guillemin G. (2007) The involvement of astrocytes and kynurenine pathway in Alzheimer's disease. Neurotox. Res. 12, 247 262.
61. Tonnaer J. A., Cheung C. L. De Boer T. (1991) cGMP formation and phosphoinositide turnover in rat brain slices are mediated by pharmacologically distinct muscarinic acetylcholine receptors. Eur. J. Pharmacol. 207, 183 188.
62. Vane J. R., Bakhle Y. S. Botting R. M. (1998) Cyclooxygenases 1 and 2. Annu. Rev. Pharmacol. Toxicol. 38, 97 120.
63. in t' Veld B. A., Ruitenberg A., Hofman A., Launer L. J., van Duijn C. M., Stijnen T., Breteler M. M. Stricker B. H. (2001) Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N. Engl. J. Med. 345, 1515 1521.
64. Venault P., Chapouthier G., de Carvalho L. P., Simiand J., Morre M., Dodd R. H. Rossier J. (1986) Benzodiazepine impairs and beta-carboline enhances performance in learning and memory tasks. Nature 321, 864 866.
65. Vitolo O. V., Sant'Angelo A., Costanzo V., Battaglia F., Arancio O. Shelanski M. (2002) Amyloid beta -peptide inhibition of the PKA/CREB pathway and long-term potentiation: reversibility by drugs that enhance cAMP signaling. Proc. Natl Acad. Sci. USA 99, 13217 13221.
66. Wallace J. L., Reuter B., Cicala C., McKnight W., Grisham M. B. Cirino G. (1994) Novel nonsteroidal anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat. Gastroenterology 107, 173 179.
67. Wallace J. L., Muscara M. N., de Nucci G., Zamuner S., Cirino G., del Soldato P. Ongini E. (2004) Gastric tolerability and prolonged prostaglandin inhibition in the brain with a nitric oxide-releasing flurbiprofen derivative, NCX-2216 [3-[4-(2-fluoro-alpha-methyl-[1,1′-biphenyl]-4-acetyloxy)-3- methoxyphenyl] -2-propenoic acid 4-nitrooxy butyl ester]. J. Pharmacol. Exp. Ther. 309, 626 633.
68. Walsh D. M., Klyubin I., Fadeeva J. V., Cullen W. K., Anwyl R., Wolfe M. S., Rowan M. J. Selkoe D. J. (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535 539.
69. Weggen S., Eriksen J. L., Das P. et al. (2001) A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 414, 212 216.
70. Wenk G. L., Rosi S., McGann K. Hauss-Wegrzyniak B. (2002) A nitric oxide-donating flurbiprofen derivative reduces neuroinflammation without interacting with galantamine in the rat. Eur. J. Pharmacol. 453, 319 324.
71. Wilcock D. M., Jantzen P. T., Li Q., Morgan D. Gordon M. N. (2007) Amyloid-beta vaccination, but not nitro-nonsteroidal anti-inflammatory drug treatment, increases vascular amyloid and microhemorrhage while both reduce parenchymal amyloid. Neuroscience 144, 950 960.
72. Wilcock G. K., Black S. E., Hendrix S. B., Zavitz K. H., Swabb E. A. Laughlin M. A. (2008) Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. Lancet Neurol. 7, 483 493.
73. Yang P., Felix E., Madden T., Fischer S. M. Newman R. A. (2002) Quantitative high-performance liquid chromatography/electrospray ionization tandem mass spectrometric analysis of 2- and 3-series prostaglandins in cultured tumor cells. Anal. Biochem. 308, 168 177.