Enhanced Activation of NF-κB Signaling by Apolipoprotein E4

  • Gal Ophir
  • Liza Mizrahi
  • Daniel M. Michaelson
Part of the Advances in Behavioral Biology book series (ABBI, volume 57)


Microglial Activation ApoE Genotype Human ApoE3 ApoE4 Mouse ApoE3 Transgenic Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. McGeer EG, McGeer PL. Inflammatory processes in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:741–749.PubMedCrossRefGoogle Scholar
  2. Eikelenboom P, van Gool WA. Neuroinflammatory perspectives on the two faces of Alzheimer's disease. J Neural Transm 2004;111:281–294.PubMedCrossRefGoogle Scholar
  3. Rogers JT, Lahiri DK. Metal and inflammatory targets for Alzheimer's disease. Curr Drug Targets 2004;5:535–551.PubMedCrossRefGoogle Scholar
  4. Roses D. Apolipoprotein E alleles as risk factors in Alzheimer's disease. Annu Rev Med 1996;47:387–400.PubMedCrossRefGoogle Scholar
  5. Egensperger R, Kosel S, von Eitzen U, Graeber MB. Microglial activation in Alzheimer disease: association with APOE genotype. Brain Pathol 1998;8:439–447.PubMedCrossRefGoogle Scholar
  6. Ophir G, Amarglio N, Jacob-Hirsch J, et al. Apolipoprotein E4 enhances brain inflammation by modulation of the NF-kB signaling cascade. Neurobiol Dis 2005;20:709–718.PubMedCrossRefGoogle Scholar
  7. Sabo T, Lomnitski L, Nyska A, et al. Susceptibility of transgenic mice expressing human apolipoprotein E to closed head injury, the allele E3 is neuroprotective whereas E4 increases fatalities. Neuroscience 2000;101:879–884.PubMedCrossRefGoogle Scholar
  8. Murphy MM, Mirtasinovic OM, Sullivan PM. Microarray comparison of gene expression in the hippocampus of aged apoE3 and E4 transgenic mice. Neurobiol Aging 2004;25:316–320.CrossRefGoogle Scholar
  9. Xu PT, Schmechel D, Rothrock-Christian T, et al. Human apolipoprotein E2, E3, and E4 isoform-specific transgenic mice, human-like pattern of glial and neuronal immunoreactivity in central nervous system not observed in wild-type mice. Neurobiol Dis 1996;3:229–245.PubMedCrossRefGoogle Scholar
  10. Ophir G, Meilin S, Efrati M, et al. Human apoE3 but not apoE4 rescues impaired astrocyte activation in apoE null mice. Neurobiol Dis 2003;12:56–64.PubMedCrossRefGoogle Scholar
  11. Hanada T, Yoshimura A. Regulation of cytokine signaling and inflammation. Cytokine Growth Factor Rev 2002;13:413–421.PubMedCrossRefGoogle Scholar
  12. Reichart F, Rotshenker S. Deficient activation of microglia during optic nerve degeneration. J Neuroimmunol 1996;70:153–161.CrossRefGoogle Scholar
  13. Rotshenker S. Microglia and macrophage activation and the regulation of complement-receptor-3 (CR3/MAC-1)-mediated phagocytosis in injury and disease. J Mol Neurosci 2003;21:65–72.PubMedCrossRefGoogle Scholar
  14. Laskowitz DT, Goel S, Bennett ER, Matthew WD. Apolipoprotein E suppresses glial cell secretion of TNF alpha. J Neuroimmunol 1997;76:70–74.PubMedCrossRefGoogle Scholar
  15. Barger SW, Harmon AD. Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature 1997;388:878–881.PubMedCrossRefGoogle Scholar
  16. Lynch JR, Morgan D, Mance J, et al. Apolipoprotein E modulates glial activation and the endogenous central system inflammatory response. J Neuroimmunol 2001;114:107–113.PubMedCrossRefGoogle Scholar
  17. Colton CA, Brown CM, Czapiga M, Vitek MP. Apolipoprotein-E allele-specific regulation of nitric oxide production. Ann N Y Acad Sci 2002;962:212–225.PubMedCrossRefGoogle Scholar
  18. Guo L, LaDu MJ, Van Eldik LJ. A dual role for apolipoprotein E in neuroinflammation, anti- and pro-inflammatory activity. J Mol Neurosci 2004;23:205–212.PubMedCrossRefGoogle Scholar
  19. Chen S, Averett WT, Manelli A, et al. Isoform-specific effects of apolipoprotein E on secretion of inflammatory mediators in adult rat microglia. J Alzheimers Dis 2005;7:25–35.PubMedGoogle Scholar
  20. Mirzoeva S, Koppal T, Petrova TV, et al. Screening in a cell-based assay for inhibitors of microglial nitric oxide production reveals calmodulin-regulated protein kinases as potential drug discovery targets. Brain Res 1999;844:126–134.PubMedCrossRefGoogle Scholar
  21. Trushin SA, Pennington KN, Algeciras-Schimnich A, Paya CV. Protein kinase C and calcineurin synergize to activate IkappaB kinase and NF-kappaB in T lymphocytes. J Biol Chem 1999;74:22923–22931.CrossRefGoogle Scholar
  22. Suo Z, Wu M, Citron BA, et al. Persistent protease-activated receptor-4 signaling mediates thrombin-induced microglial activation. J Biol Chem 2003;278:31177–31183.PubMedCrossRefGoogle Scholar
  23. Kim Y, Moon JS, Lee KS, et al. Ca2+/calmodulin-dependent protein phosphatase calcineurin mediates the expression of iNOS through IKK and NF-kappaB activity in LPS-stimulated mouse peritoneal macrophages and RAW 264.7 cells. Biochem Biophys Res Commun 2004;314:695–703.PubMedCrossRefGoogle Scholar
  24. Muller W, Meske V, Berlin K, et al. Apolipoprotein E isoforms increase intracellular Ca2+ differentially through an omega-agatoxin IVa-sensitive Ca2+-channel. Brain Pathol 1998;8:641–653.PubMedCrossRefGoogle Scholar
  25. Bacskai BJ, Xia MQ, Strickland DK, et al. The endocytic receptor protein LRP also mediates neuronal calcium signaling via N-methyl-d-aspartate receptors. Proc Natl Acad Sci U S A 2000;97:11551–11556.PubMedCrossRefGoogle Scholar
  26. Veinbergs I, Everson A, Sagara Y, Masliah E. Neurotoxic effects of apolipoprotein E4 are mediated via dysregulation of calcium homeostasis. J Neurosci Res 2002;67:379–387.PubMedCrossRefGoogle Scholar
  27. Qiu Z, Crutcher KA, Hyman BT, Rebeck GW. ApoE isoforms affect neuronal N-methyl-d-aspartate calcium responses and toxicity via receptor-mediated processes. Neuroscience 2003;122:291–303.PubMedCrossRefGoogle Scholar
  28. Noguchi T, Noguchi M, Masubuchi H, et al. IL-1β down-regulates tissue type plasminogen activation by up regulating low density lipoprotein receptor-related protein in AML 12 cells. Biochem Biophys Res Commun 2001;288:42–48.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Gal Ophir
    • 1
  • Liza Mizrahi
  • Daniel M. Michaelson
  1. 1.Department of Neurobiochemistry, George S. Wise Faculty of Life SciencesTel Aviv UniversityTel Aviv 69978Israel

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