Cyclooxygenase-2 Expression and Activity are Induced by Amyloid-Beta 1-42 in Brain-Derived Cells

  • MacKenzie Hilfers Bilunas
  • Steven A. Moore
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)


One of the early events in Alzheimer’s disease (AD) is the extracellular deposition of amyloid-beta peptide (An), a 39- to 43- amino acid cleavage product of the transmembrane glycoprotein, amyloid precursor protein. Excess A13 within the brain has long been thought to play a major role in AD pathogenesis, however, the mechanisms of its actions are highly debatable. Recent evidence suggests that inflammation may be the pathogenetic link between AP deposition and neuronal death (Halliday et al., 2000).


Ribonuclease Protection Assay Cerebral Endothelium Essential Fatty Acid Precursor Cerebrovascular Cell Vascular Cell Culture 
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  1. 1.
    Chang J., Coleman P., O’Banion K., 1996, Prostaglandin G/H synthase-2 (cyclooxygenase-2) mRNA expression is decreased in Alzheimer’s diseaseNeurobiol. Aging.17:801.PubMedCrossRefGoogle Scholar
  2. 2.
    Chiang C., Stalder A., Samimi A., Campbell I.L., 1994, Reactive gliosis as a consequence of interleukin-6 expression in the brain: Studies in transgenic miceDev. Neurosci.16:212.PubMedCrossRefGoogle Scholar
  3. 3.
    Goodwin D., Landino L., Marnett L., 1999, Effects of nitric oxide and nitric oxide-derived species on prostaglandin endoperoxide synthase and prostaglandin biosynthesis, FASEB. 13:1121.Google Scholar
  4. 4.
    Halliday G., Robinson S., Shepherd C., Kril J., 2000, Alzheimer’s disease and inflammation: a review of cellular and therapeutic mechanismsClin. Exp. Pharmacol. Physiol.27:1.PubMedCrossRefGoogle Scholar
  5. 5.
    Ho L., Pieroni C., Winger D., Purohit D., Aisen P., Pasinetti G., 1999, Regional distribution of cyclooxygenase-2 in the hippocampal formation in Alzheimer’s diseaseJ. Neurosci. Res.57:295.PubMedCrossRefGoogle Scholar
  6. 6.
    Hu J., Akama K., Krafft G., Chromy B., Van Eldik L., 1998, Amyloid-ß peptide activates cultured astrocytes: morphological alterations, cytokine induction and nitric oxide releaseBrain Res.785:195.PubMedCrossRefGoogle Scholar
  7. 7.
    Johnstone M., Gearing A., Miller K., 1999, A central role for astrocytes in the inflammatory response to beta-amyloid; chemokines, cytokines and reactive oxygen species are producedJ. Neuroimmunol.93:182.PubMedCrossRefGoogle Scholar
  8. 8.
    Landolfi C., Soldo L., Polenzani L., Apicella C., de Joannon A., Coletta I., Di Cesare F.M., Pinza, M., Milanese C.,1998, Inflammatory molecule release by ß-amyloid-treated T98G astrocytoma cells: role of prostaglandins and modulation by paracetamolEur. J. Pharmacol.360:55.PubMedCrossRefGoogle Scholar
  9. 9.
    McGeer P., Schulzer M., McGeer E.,1996, Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: A review of 17 epidemiologic studiesNeurol.47:425.CrossRefGoogle Scholar
  10. 10.
    Mitchell J. and Warner T., 1999, Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapyBr. J. Pharmacol.128:1121.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Moore S.A., Strauch A., Yoder E., Rubenstein P., Hart M.,1984, Cerebral microvascular smooth muscle in tissue cultureIn Vitro.20:512.PubMedCrossRefGoogle Scholar
  12. 12.
    Moore S.A., Yoder E., and Spector A.,1990, Role of the blood-brain barrier in the formation of long-chain w-3 and w-6 fatty acids from essential fatty acid precursors.J. Neurochem.55:391.PubMedCrossRefGoogle Scholar
  13. 13.
    Moore S.A., Yoder E., Murphy S., Dutton G., Spector A.,1991, Astrocytes, not neurons, produce docosahexaenoic acid (22:6w-3) and arachidonic acid (20:4w-6)J. Neurochem.56:518.PubMedCrossRefGoogle Scholar
  14. 14.
    Moore S.A., Yoder E., Rich G., Hilfers M., Albright J.,1999, Regulation of cerebrovascular cyclooxygenase-2 by pro-and anti-inflammatory cytokines.Adv. Exp. Med. Biol.69:647.Google Scholar
  15. 15.
    O’Banion M., Miller J., Chang J., Kaplan M., Coleman P.,1996, Interleukin-113 induces prostaglandin G/H synthase-2 (cyclooxygenase-2) in primary mucine astrocyte culturesJ. Neurochem.66: 2532.PubMedCrossRefGoogle Scholar
  16. 16.
    Pasinetti G.,1998, Cyclooxygenase and inflammation in Alzheimer’s disease: Experimental approaches and clincial interventionsJ. Neurosci. Res.54:1.PubMedCrossRefGoogle Scholar
  17. 17.
    Pasinetti G. and Aisen P., 1998, Cyclooxygnease-2 expression is increased in frontal cortex of Alzheimer’s disease brainNeurology87:319.Google Scholar
  18. 18.
    Price J., Sutton E., Hellermann A., Thomas T.,1997, (3 -amyloid induces cerebrovascular endothelial dysfunction in the rat brainNeurol. Res.19:534.PubMedGoogle Scholar
  19. 19.
    Su G., Arendash G., kalaria R., Bjugstad K., Mullan M.,1999, Intravascular infusions of soluble 13amyloid compromise the blood-brain barrier, activate CNS glial cells and induce peripheral hemorrhageBrain Res.818:105.PubMedCrossRefGoogle Scholar
  20. 20.
    Weldon D., Rogers S., Ghilardi J., Finke M., Cleary J., O’Hare E., Esler W., Maggio J., Mantyh P.,1998, Fibrillar (3-amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivoJ. Neuro.18:2161.Google Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • MacKenzie Hilfers Bilunas
    • 1
  • Steven A. Moore
    • 1
  1. 1.Department of PathologyThe University of IowaIowa CityIA

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