Molecular Neurobiology

, Volume 17, Issue 1–3, pp 73–86

Cellular and molecular basis of estrogen’s neuroprotection

Potential relevance for Alzheimer’s disease
  • Nibaldo C. Inestrosa
  • Maria-Paz Marzolo
  • Andrea B. Bonnefont
Original Articles

Abstract

Alzheimer’s disease (AD) is one of the most common types of dementia among the aged population, with a higher prevalence in women. The reason for this latter observation remained unsolved for years, but recent studies have provided evidence that a lack of circulating estrogen in postmenopausal women could be a relevant factor.

Moreover, follow-up studies among postmenopausal women who had received estrogenreplacement therapy (ERT), suggested that they had a markedly reduced risk of developing AD. In addition, studies among older women who already had AD indeed confirmed that a decrease in estrogen levels was likely to be an important factor in triggering the pathogenesis of the disease.

In this review article, we will discuss the evidence suggesting that estrogen may have a protective role against AD, mainly through its action as: a trophic factor for cholinergic neurons, a modulator for the expression of apolipoprotein E (ApoE) in the brain, an antioxidant compound decreasing the neuronal damage caused by oxidative stress, and a promoter of the physiological nonamyloidogenic processing of the amyloid precursor protein (APP), decreasing the production of the amyloid-Β-peptide (AΒ), a key factor in the pathogenesis of AD.

Index Entries

Neuroprotection estrogen cholinergic neurons apolipoprotein E APP processing oxidative stress Alzheimer’s disease 

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References

  1. Alvarez J., Moreno R. D., and Inestrosa N. C. (1995) Mitosis of Schwan cells and demyelination are induced by the amyloid precursor protein and other protease inhibitors in the rat sciatic nerve.Eur. J. Neurosci. 7, 152–159.PubMedGoogle Scholar
  2. Bachman D. K., Wolf P. A., and Linn R. (1992) Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham study.Neurology 42, 115–119.PubMedGoogle Scholar
  3. Banker G. A. (1980) Trophic interactions between astroglial cells and hippocampal neurons in culture.Science 209, 809–810.PubMedGoogle Scholar
  4. Behl C., Davis J., Lesley R., and Schunbert D. (1994) Hydrogen peroxide mediates amyloid-beta protein toxicity.Cell 77, 817–827.PubMedGoogle Scholar
  5. Behl C., Davis J., Cole G. M., and Schubert D. (1992) Vitamin E protects nerve cells from amyloid-beta protein toxicity.Biochem. Biophys. Res. Commun. 186, 944–990.PubMedGoogle Scholar
  6. Behl C., Thomas S., Lezoulac’h F., Post A., Widmann M., Newton C. J., and Holsboer F. (1997) Neuroprotection against oxidative stress by estrogen: structure-activity relationship.Mol. Pharmacol. 51, 535–541.PubMedGoogle Scholar
  7. Behl C. W., Widman M. T., and Holsboer F. (1995) 17-beta-estradiol protects neurons from oxidative stress-induced cell death in vitro.Biochem. Biophys. Res. Commun. 216, 473–478.PubMedGoogle Scholar
  8. Bellosta S., Nathan B. P., Orth M., Dong L. M., Mahley R. W., and Pitas R. E. (1995) Stable expression and secretion of apolipoproteins E3 and E4 in mouse neuroblastoma cells produces differential effects on neurite outgrowth.J. Biol. Chem. 270, 27,063–27,071.Google Scholar
  9. Bertrand P., Poirier J., Tomiichiro O., Finch C. E., and Pasinetti G. M. (1995) Association of apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clustering) in Alzheimer disease.Mol. Brain Res. 33, 174–178.PubMedGoogle Scholar
  10. Birge S. J. (1996) Is there a role of estrogen replacement therapy in the prevention and treatment of dementia?J. Amer. Geriat. Soc. 44, 865–870.PubMedGoogle Scholar
  11. Blass J. P. and Poirier J. (1996) Pathology of the Alzheimer syndrome, inClinical Diagnosis and Management of Alzheimer’s Disease, (Gauthier S., ed.) Martin Dunitz Press, London, pp. 17–31.Google Scholar
  12. Boyles J. K., Zoellner C. D., Anderson L. J., Kosick L. M., Pitas R. E., Hui D. Y., Mahley R. W., Gebicke-Haerter P. J., Ignatius M. J., and Shooter E. M. (1989) A role for apolipoprotein E, apolipoprotein A-1, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelinization of the rat sciatic nerve.J. Clin. Invest. 83, 1015–1031.PubMedGoogle Scholar
  13. Braughler J. M. and Pregenzer J. F. (1989) The 21-aminosteroid inhibitors of lipid peroxidation: reactions with lipid peroxyl and phenoxy radicals.Free Rad. Biol. Med. 7, 125–130.PubMedGoogle Scholar
  14. Breedlove S. M. (1992) Sexual dimorphism in the vertebrate nervous system.J. Neurosci. 12, 4133–4142.PubMedGoogle Scholar
  15. Breen K., Bruce M., and Anderton B. H. (1991) Betaamyloid precursor protein mediates neuronal cell-cell and cell-surface adhesion.J. Neurosci. Res. 28, 90–100.PubMedGoogle Scholar
  16. Bronfman F. C., Soto C., Tapia L., Tapia V., and Inestrosa N. C. (1996) Extracellular matrix regulates the amount of the beta-amyloid precursor protein and its amyloidogenic fragments.J. Cell. Physiol. 166, 360–369.PubMedGoogle Scholar
  17. Brown R. H. (1995) Amyotrophic lateral sclerosis: recent insights from genetics and transgenic mice.Cell 80, 687–695.PubMedGoogle Scholar
  18. Bu G., Maksymovitch E. A., Nerbonne J. M., and Schwartz A. L. (1994) Expression and function of the low density lipoprotein receptor-related protein (LRP) in mammalian central neurons.J. Biol. Chem. 269, 18,521–18,528.Google Scholar
  19. Carpenter M. K., Hassinger T. D., Whalen L. R., and Kater S. B. (1994) CNS white matter can be altered to support neuronal outgrowth.J. Neurosci. Res. 37, 1–14.PubMedGoogle Scholar
  20. Chen M. and Yankner B. A. (1991) An antibody to beta-amyloid and the amyloid precursor inhibits cell-substratum adhesion in many mammalian cell types.Neurosci. Lett. 125, 223–226.PubMedGoogle Scholar
  21. Christie R. H., Chung H., Rebeck G. W., Strickland D., and Hyman B. (1996) Expression of the very low-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer’s disease.J. Neuropathol. Exp. Neurol. 55, 491–498.PubMedGoogle Scholar
  22. Copain A., Koh J. Y., and Cotman C. W. (1991) Betaamyloid increases neuronal susceptibility to injury by glucose deprivation.NeuroReport 2, 763–765.Google Scholar
  23. Corder E. H., Saunders A. M., Strittmatter W. J., Schmechel D. E., Gaskell P. C., Small G. W., Roses A. D., Haines J. L., and Pericak-Vance M. A. (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families.Science. 261, 921–923.PubMedGoogle Scholar
  24. Corder E. H., Saunders A. M., Strittmatter W. J., Schmechel D. E., Gaskell P. C., Jr., Rimmler J. B., Locke P. A., Conneally P. M., Schmader K. E., and Tanzi R. E. (1995) Apolipoprotein E, survival in Alzheimer’s disease patients, and the competing risks of death and Alzheimer’s disease.Neurology 45, 1323–1328.PubMedGoogle Scholar
  25. Coyle J. T. and Puttfarken P. (1993) Oxidative stress, glutamate and neurodegenerative disorders.Science 262, 689–695.PubMedGoogle Scholar
  26. Das S. K., Taylor J. A., Korach K. S., Paria B. C., Dey S. K., and Lubahn D. B. (1997) Estrogenic responses in estrogen-α deficient mice reveal a distinct estrogen signaling pathway.Proc. Natl. Acad. Sci. USA 94, 12,786–12,791.Google Scholar
  27. Dickson R. B., Mc Manaway M. E., and Lippman M. E. (1986) Estrogen-induced factors of breast cancer cells partially replace estrogen to promote tumor growth.Science 232, 1540–1543.PubMedGoogle Scholar
  28. Drouva S. V., Gorenne I., Laplante E., Rerat E., Enjalbert A., and Kordon C. (1990) Estradiol modulates protein kinase C activity in the rat pituitary in vivo and in vitro.Endocrinology 126, 536–544.PubMedGoogle Scholar
  29. Elkabes S., DiCicco-Bloom E. M., and Black I. B. (1996) Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function.J. Neurosci. 16, 2508–2521.PubMedGoogle Scholar
  30. Elshourbagy N. A., Liao W. S., Mahley R. W., and Taylor J. M. (1985) Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets.Proc. Natl Acad. Sci. USA 82, 203–207.PubMedGoogle Scholar
  31. Evans R. M. (1988) The steroid and thyroid receptor superfamily.Science 240, 889–895.PubMedGoogle Scholar
  32. Fillit H., Weinreb H., Cholst I., Luine V., Mc Ewen B., Amador R., and Zabriskie J. (1986). Observation in a preliminary open trial of estradiol therapy for senile dementia: Alzheimer’s type.Psychoneuroendocrinology 11, 337–345.PubMedGoogle Scholar
  33. Fisher W., Gage F., and Bjorklund A. (1989) Degenerative changes in forebrain cholinergic nuclei correlate with cognitive impairments in aged rats.Eur. J. Neurosci. 1, 34–35.Google Scholar
  34. Garcia-Segura L. M., Chowen J. A., Párducz, A., and Naftolin F. (1994) Gonadal hormones as promoters of structural synaptic plasticity: cellular mechanisms.Prog. Neurobiol. 44, 279–307.PubMedGoogle Scholar
  35. Gibbs R. B. (1994) Estrogen and nerve growth factor related systems in brain.Ann. NY Acad. Sci. 743, 165–199.PubMedGoogle Scholar
  36. Gibbs R. B. (1997) Effects of estrogen on basal forebrain cholinergic neurons vary as a function of dose and duration of treatment.Brain Res. 757, 10–16.PubMedGoogle Scholar
  37. Haass C. and Selkoe D. J. (1993) Cellular processing of beta-amyloid precursor protein and the genesis of amyloid-beta-peptide.Cell 75, 1039–1042.PubMedGoogle Scholar
  38. Hall E. D., Pazara K. E., and Linseman K. L. Sex differences in postischemic neuronal necrosis in gerbils.J. Cereb. Blood Flow Metab. 11, 292–298.Google Scholar
  39. Henderson V., Paganini-Hill A. A., Emanuel C. K., Dunn M. E., and Buckwelker J. G. (1994) Estrogen replacement therapy in older women: comparison between Alzheimer’s disease cases and nondemented controls.Arch. Neurol. 51, 896–899.PubMedGoogle Scholar
  40. Honjo H., Ogino Y., Naitoh K., Urabe M., Kitawaki J., Yasuda J., Yamamoto T., Ishihara S., Okada H., Yonezawa T., Hayashi K., and Nambara T. (1989) In vivo effects by estrone sulfate on the central nervous system: senile dementia (Alzheimer’s type).J. Steroid Biochem. 34, 521–525.PubMedGoogle Scholar
  41. Honjo J., Tamura T., Matsumoto Y., Kawata M., Ogino Y., Tamaka K., Yamamoto T., Ueda S., and Okado H. (1992) Estrogen as a growth factor to central nervous cells.J. Steroid. Biochem. 41, 633–635.Google Scholar
  42. Ishiguro M., Imai Y., and Kohsaka S. (1995) Expression and distribution of low density lipoprotein receptor-related protein mRNA in the rat central nervous system.Brain Res. Mol. Brain Res. 33, 37–46.PubMedGoogle Scholar
  43. Jaffe A. B., Torand-Allerand C. D., Greengard P., and Gandy S. E. (1994) Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein.J. Biol. Chem. 269, 13,065–13,068.Google Scholar
  44. Jing S., Tapley P., and Barbacid M. (1992) Nerve growth factor mediates signal transduction through trk homodimer receptors.Neuron 9, 1067–1079.PubMedGoogle Scholar
  45. Jones K. J. (1988) Steroid hormones and neurotrophism: relationship to nerve injury.Metab. Brain. Dis. 3, 1–18.PubMedGoogle Scholar
  46. Kaplan D. R., Martin-Zanca D., and Parada L. F. (1991a) Tyrosine phosphorylation and tyrosine kinase activity of the trk-proto-oncogene produced by NGF.Nature 350, 158–160.PubMedGoogle Scholar
  47. Kaplan D. R., Hempstead B., Martin-Zanca D., Chao M. V., and Parada L. F. (1991b) The trk proto-oncogene product: a signal transducing receptor for nerve growth factor.Science 252, 554–558.PubMedGoogle Scholar
  48. Kibbey M. C., Jucker M., Weeks B. S., Neve R. L., Van Norstrand W. E., and Kleinman H. K. (1993) Beta-amyloid precursor protein binds to neuritepromoting IKVAV site of Laminin.Proc. Natl. Acad. Sci. USA 90, 10,150–10,153.Google Scholar
  49. Kim D. H., Iijima H., Goto K., Sakai J., Ishii H., Kim H. J., Suzuki H., Kondo H., Saeki S., and Yamamoto T. (1996) Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain.J. Biol. Chem. 271, 8373–80.PubMedGoogle Scholar
  50. Koh J. Y., Yang L. L., and Cotman C. W. (1990) Betaamyloid protein increases the vulnerability of culture cortical neurons to excitotoxic damage.Brain. Res. 533, 315–320.PubMedGoogle Scholar
  51. Korach K. S. (1994) Insights from the study of animals lacking functional estrogen receptor.Science 266, 1524–1527.PubMedGoogle Scholar
  52. Kuiper G. G., Enmark E., Pelto-Huikko M., Nilsson S., and Gustafsson J. A. (1996) Cloning of a novel estrogen receptor expressed in rat prostate and ovary.Proc. Natl. Acad. Sci. USA 93, 5925–5930.PubMedGoogle Scholar
  53. Kushwaha R. S., Foster D. M., Barrett K. D., Carey K. D., and Bernard M.G. (1991) Metabolic regulation of plasma apolipoprotein E by estrogen and progesterone in the baboon (Papio sp.).Metabolism 40, 93–100.PubMedGoogle Scholar
  54. Landers J. P. and Spelsberg T. C. (1992) New concepts in steroid hormone action: transcription factors, proto-oncogenes, and the cascade model for steroid regulation of gene expression.Crit. Rev. Eukaryotic Gene Expression 2, 19–63.Google Scholar
  55. Lobo R. A. (1995) Benefits and risks of estrogen replacement therapy.Arn. J. Obstet. Gynecol. 173, 982–989.Google Scholar
  56. Lockhart B. P., Benicourt C., Junien J.-L., and Privat A. (1994) Inhibition of free radical formation fail to alternate direct beta-amyloid peptide-mediated neurotoxicity in rat hippocampal cultures.J. Neurosci. Res. 39, 494–505.PubMedGoogle Scholar
  57. Lubahn D. B., Moyer J. S., Golding T. S., Course J. F., Korach K. S., and Smities O. (1993) Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene.Proc. Natl. Acad. Sci. USA 90, 11162–11166.PubMedGoogle Scholar
  58. Luine V. N. (1992) Estradiol increases choline acetyl transferase activity in specific basal forebrain nuclei and projection area of female rats.Exp. Neurol. 89, 484–490.Google Scholar
  59. Lustig R. H. (1994) Anin vitro model for the effects of estrogen on neurons employing estrogen receptor-transfected PC12 cells.J. Neurosci. 14, 3945–3957.PubMedGoogle Scholar
  60. Mahley R. W. (1989) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.Science 240, 622–630.Google Scholar
  61. Mahley R. W. (1996) Heparan sulfate proteoglycan/low density lipoprotein receptor-related protein pathway involved in type III hyperlipoproteinemia and Alzheimer’s disease.Isr. J. Med. Sci. 32, 414–29.PubMedGoogle Scholar
  62. Maizels E. T., Miller J. B., Cutler R. J., Jackiw V., Carney E. M., Mizuno K., Ohno S., and Hunzicker D. M. (1992) Estrogen modulates Ca2[female]-independent lipid-stimulated kinase in the rabbit corpus luteum of pseudopregnancy. Identification of luteal estrogen-modulated lipid-stimulated kinase as protein kinase C delta.J. Biol Chem. 267, 17,061–17,068.Google Scholar
  63. Masliah E., Mallory M., Ge N., Alford M., Veinbergs I., and Rose A. D. (1995) Neurodegeneration in the central nervous system of apoE-deficient mice.Exp. Neurol. 136, 107–122.PubMedGoogle Scholar
  64. Mattson M. P., Cheng B., Davis D., Bryant K., Lieberburg I., and Rydel R. E. (1992) Beta-amyloid peptide destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity.J. Neurosci. 12, 376–389.PubMedGoogle Scholar
  65. Mc Ewen B. S. (1981) Endocrine effects on the brain and their relationship to behavior, inBasic Neurochemistry, 3rd ed. Little Crown & Co., Boston pp. 775–799.Google Scholar
  66. Mc Ewen B. S. (1988) Steroid hormones in the brain: linking nature and nurture.Neurochem. Res. 13, 663–669.Google Scholar
  67. Mc Ewen B. S., Coirini H., Danielsson A., Frankfurt M., Gould E., Mendelson S., Segarra A., and Wooley C. (1991) Steroid and thyroid hormones modulate a changing brain.J. Steroid Biochem. Mol Biol. 40, 1–14.Google Scholar
  68. Mc Ewen B. S., de Kloet E. R., and Rostene W. (1986) Adrenal steroid receptors and actions in the nervous system.Physiol. Rev. 66, 1121–1188.Google Scholar
  69. Mc Ewen B. S., Gerlach J. L., and Micco D. J. (1975) Putative glucocorticoid receptors in hippocampus and other regions of the rat brain, inThe Hippocampus: A Comprehensive Treatise. (Issacson, R. and Pribramm, K., eds.) Plenum, New York, pp. 285–322.Google Scholar
  70. Mc Ewen B. S., Zigmond R. E., and Gerlach J. (1972) Sites of steroid binding and action in the brain, inStructure and Function of Nervous Tissue, vol. 5. (G.H. Bourne, ed.) Academic, New York. pp. 205–291.Google Scholar
  71. Mecocci P. L., MacGarvey U., and Beal M. F. (1994) Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease.Ann. Neurol. 36, 747–750.PubMedGoogle Scholar
  72. Miranda R. C. and Toran-Allerand C. D. (1992) Developmental expression of estrogen receptor mRNA in the rat cerebral cortex: a nonisotopic in situ hybridization histochemistry study.Cereb. Cortex 2, 1–15.PubMedGoogle Scholar
  73. Miranda R., Sohrabji F., Singh M., and Toran-Allerand C. D. (1996) Nerve growth factor (NGF) regulation of estrogen receptors in expiant cultures of the developing forebrain.J. Neurobiol. 31, 77–87.PubMedGoogle Scholar
  74. Milward E. A., Papadopoulos R., Fuller S. J., Moir R. D., Small D., Beyreuther K., and Masters C. L. (1992) The amyloid precursor protein of AD is a mediator of the effects of nerve growth factor on neurite outgrowth.Neuron 9, 129–137.PubMedGoogle Scholar
  75. Milward E. A., Papadopoulos R., Fuller S. J., Moir R. D., Small D., Beyreuther K., and Masters C. L. (1992) The amyloid precursor protein of AD is a mediator of the effects of nerve growth factor on neurite outgrowth.Neuron 9, 129–137.PubMedGoogle Scholar
  76. Mosselman S., Polman J., Djikema R. (1996) ERΒ: identification and characterization of a novel human estrogen receptor.FEBS Lett. 392, 49–53.PubMedGoogle Scholar
  77. Mukai K., Daifuku K., and Yokoyama S. (1990) Stopped-flow investigation of antioxidant activity of estrogen in solution.Biochem. Biophys. Acta. 1035, 348–352.PubMedGoogle Scholar
  78. Nakai M., Kawamata T., Taniguchi T., Maeda K., and Tanaka C. (1996) Expression of apolipoprotein E mRNA in rat microglia.Neurosci. Lett. 211, 41–44.PubMedGoogle Scholar
  79. Namba Y., Tomonaga M., Kawasaki H., Otomo E., and Ikeda L. (1991) Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease and kuru plaque amyloid in Creutzfeldt-Jacob disease.Brain. Res. 541, 163–166.PubMedGoogle Scholar
  80. Narita M., Bu G., Holtzman D. M., and Schwartz A. L. (1997) The low-density lipoprotein receptorrelated protein, a multifunctional apolipoprotein E receptor, modulates hippocampal neurite development.J. Neurochem. 68, 587–595.PubMedGoogle Scholar
  81. Nathan B. P., Bellosta S., Sanan D. A., Weisgraber K. H., Mahley R. W., and Pitas R. E. (1994) Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro.Science 264, 850–852.PubMedGoogle Scholar
  82. Newton C. J., Trapp T., and Pagotto U. (1994) The estrogen receptor modulates growth of pituitary tumor cells in the absence of exogenous estrogen.J. Mol. Endocrinol. 12, 303–312.PubMedGoogle Scholar
  83. Pace P., Taylor J., Suntharalingam S., Coombes R. C., and Ali S. (1997) Human estrogen receptor Β binds DNA in a manner similar to and dimerizes with estrogen receptor α.J. Biol. Chem. 272, 25,832–25,838.Google Scholar
  84. Paganini-Hill A. and Henderson V. W. (1994) Estrogen deficiency increases the risk of Alzheimer’s disease in women.Am. J. Epidemol. 140, 256–261.Google Scholar
  85. Paganini-Hill A. and Henderson V. W. (1996) Estrogen replacement therapy and risk of Alzheimer disease.Arch. Intern. Med. 156, 2213–2217.PubMedGoogle Scholar
  86. Parthasarathy S. S., Steinberg D., and Witztum J. L. (1992) The role of oxidized low-density lipoproteins in the pathogenesis of atherosclerosis.Ann. Rev. Med. 43, 219–225.PubMedGoogle Scholar
  87. Pitas R. E., Boyles J. K., Lee S. H., Foss D., and Mahley R. W. (1987) Lipoproteins and their receptors in the central nervous system-characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E (LDL) receptors in the brain.J. Biol. Chem. 262, 14,352–14,360.Google Scholar
  88. Pitas R. E., Boyles J. K., Lee S. H., Foss D., and Mahley R. W. (1987) Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein Econtaining lipoproteins.Biochim. Biophys. Acta 917, 148–161.PubMedGoogle Scholar
  89. Poirier J. (1994) Apolipoprotein E in animal models of CNS injury and in Alzheimer’s disease.Trends Neurosci. 17, 525–530.PubMedGoogle Scholar
  90. Poirier J., Baccichet A., Dea D., and Gauthier S. (1993) Cholesterol synthesis and lipoprotein reuptake during synaptic remodeling in hippocampus in adult rats.Neuroscience 55, 81–90.PubMedGoogle Scholar
  91. Poirier J., Davignon J., Bouthillier D., Kogan S., Bertrand P., and Gauthier S. (1993) Apolipoprotein E polymorphism and Alzheimer’s disease.Lancet 342, 697–699.PubMedGoogle Scholar
  92. Poirier J., Hess M., May P. C., and Finch C. E. (1991) Astrocytic apolipoprotein E mRNA and GPAP mRNA in hippocampus after etorhinal cortex lesioning.Mol. Brain Res. 11, 97–106.PubMedGoogle Scholar
  93. Puttfarcken P. S., Manelli A. M., Falduto M. T., Getz G. S., and LaDu M. J. (1997) Effect of apolipoprotein E on neurite outgrowth and Β-amyloid-induced toxicity in developing rat primary hippocampal cultures.J. Neurochem. 68, 760–769.PubMedGoogle Scholar
  94. Rebeck G. W., Reiter J. S., Strickland D. K., and Hyman B. T. (1993) Apolipoprotein E in sporadic Alzheimer’s disease: allelic variation and receptor interactions.Neuron 11, 575–580.PubMedGoogle Scholar
  95. Rifici V. and Khachadurian A. K. (1992) The inhibition of low-density lipoprotein oxidation by 17-beta estradiol.Metabolism 41, 1110–1114.PubMedGoogle Scholar
  96. Sacks F. M. and Walsh B. W. (1994) Sex hormones and lipoprotein metabolism.Curt. Opin. Lipidol. 5, 236–240.Google Scholar
  97. Saitoh T., Sundsmo M., Rock J.-M., Kimura N., Cole G., Schubert D., Oltersdorf D., and Schenk D. B. (1989) Secreted form of amyloid-beta protein precursor is involved in the growth regulation of fibroblasts.Cell 58, 615–622.PubMedGoogle Scholar
  98. Schmechel D. E., Saunders A. M., Strittmatter W. J., Crain B. J., Hulette C. M., Joo S. H., Pericak-Vance M. A., Goldgaber D., and Roses A. D. (1993) Increased amyloid Β-peptide deposition in cerebral cortex as a consequence of apolipoprotein e genotype in late-onset Alzheimer’s disease.Proc. Natl. Acad. Sci. USA 90, 9649–9653.PubMedGoogle Scholar
  99. Schubert D., Jin L.-W., Saitoh T., and Cole G. (1991) The regulation of amyloid beta-protein precursor secretion and its modulatory role in cell adhesion.Neuron 3, 689–694.Google Scholar
  100. Selkoe D. J. (1996) Amyloid-beta-protein and the genetics of Alzheimer’s disease.J. Biol. Chem. 271, 18,295–18,298.Google Scholar
  101. Selkoe D. J. (1994) Cell biology of the amyloid betaprotein precursors and the mechanism of Alzheimer’s disease.Ann. Rev. Cell. Biol. 10, 373–403.PubMedGoogle Scholar
  102. Seubert P., Oltersdorf T., Lee M. G., Barbour R., Blomguist C., Davis D. L., Bryant K., Fritz L. C., Galasco D., Thal L. J., Lieberburg I., and Schenk D. B. (1993) Secretion of Β-amyloid precursor protein cleaved at the amino-terminus of the beta-amyloid peptide.Nature 361, 260–263.PubMedGoogle Scholar
  103. Shoji M., Golde T. E., Ghiso J., Cheung T. T., Estus S., Shaffer L. M., Cai X. D., McKay D. M., Tintner R., Frangione B., and Younkin S. G. (1992) Production of the Alzheimer amyloid beta protein by normal proteolitic processing.Science 258, 126–129.PubMedGoogle Scholar
  104. Simpkins J. W., Singh M., and Bishop J. (1994) The potential role for estrogen replacement therapy in the treatment of the cognitive decline and neurodegeneration associated with Alzheimer’s disease.Neurobiol. Aging. 15, S195-S197.PubMedGoogle Scholar
  105. Smith C. D., Carney J. Ml., Starke-Reed P. E., Oliver C. N., Stadtman E. R., Floyd R. A., and Markesbery W. R. (1991) Excess brain protein oxidation and enzyme disfunction in normal aging and Alzheimer’s disease.Proc. Natl. Acad. Sci. USA 88, 10,540–10,543.Google Scholar
  106. Sohrabji F., Miranda R. C., and C. D. Toran-Allerand. (1995) Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor.Proc. Natl. Acad. Sci. USA 92, 11,110–11,114.Google Scholar
  107. Soininen H. S. and Riekkinen P. J. Sr. (1996) Apolipoprotein E, memory and Alzheimer’s disease.Trends Neurosci. 19, 224–228.PubMedGoogle Scholar
  108. Soto C., Branes M. C., Alvarez J., and Inestrosa N. C. (1994) Structural determinants of the Alzheimer’s amyloid \-peptide.J. Neurochem. 63, 1191–1198.PubMedGoogle Scholar
  109. Srivastava R. A., Bhasin N., and Srivastava N. (1996) Apolipoprotein E gene expression in various tissues of mouse and regulation by estrogen.Biochem. Mol. Biol. Int. 38, 91–101.PubMedGoogle Scholar
  110. Stephenson J. (1996) More evidence links NSAID, estrogen use with reduced Alzheimer risk.JAMA. 275, 1389–1390.PubMedGoogle Scholar
  111. Stone D. J., Rozovsky I., Morgan T. E., Anderson C. P., Hajian H., and Finch C. E. (1991) Astrocytes and microglia respond to estrogen with increased apoE mRNA in vivo and in vitro.Exp. Neurol. 143, 313–318.Google Scholar
  112. Subbarao K., Richardson J. S., and Ang L. C. (1990) Autopsy samples of Alzheimer’s cortex show increased peroxidation in vitro.J. Neurochem. 55, 342–345.PubMedGoogle Scholar
  113. Sugioka K., Shimosegawa Y., and Nakano M. (1987) Estrogen as natural antioxidant of membrane phospholipid peroxidation.FEBS Lett. 210, 37–39.PubMedGoogle Scholar
  114. Tang M.-X., Jacobs D., Stern Y., Marder K., Schofield P., Gurland B., Andrews H., and Mayeux R. (1996) Effect of estrogen during menopause on risk and age at onset of Alzheimer’s disease.Lancet. 348, 429–432.PubMedGoogle Scholar
  115. Torand-Allerand C. D., Miranda R. C., Bentham W. D. L., Sohrabji F., Brown T. J., Hochberg R. B., and MacLusky N. J. (1992) Estrogen receptors colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain.Proc. Natl. Acad. Sci. USA 89, 4668–4672.Google Scholar
  116. Van Harren F., Van Hest A., and Heinsbrock R. P. W. (1988) Behavioral differences between male and female rats: effects of gonadal hormones on learning and memory.Neurosci. Biobehav. Res. 14, 23–33.Google Scholar
  117. Weisgraber K.H. (1994) Apolipoprotein E: structure-function relationships.Adv. Protein Chem. 45, 249–302.PubMedGoogle Scholar
  118. Whitehouse P.J., Price D. L., Clark A. W., Coyle J. T., and DeLong M. R. (1981) Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis.Ann. Neurol. 10, 122–126.PubMedGoogle Scholar
  119. Wieland N. G. (1992) Estradiol selectively regulates agonist binding sites on the N-methyl-D-aspartate receptor complex in the CAI region of the hippocampus.Endocrinology 131, 662–667.Google Scholar
  120. Williams C. L. and Meek W. H. (1991) The organizational effects of gonadal steroids on sexually dimorphic spatial ability.Psychoneuroendocrinology 16, 155–176.PubMedGoogle Scholar
  121. Windier E. E., Kovanen P. J., Chao Y-S., Brown M. S., Havel R. J., and Goldstein J. L. (1980) The estradiol stimulated lipoprotein receptor of rat liver.J. Biol. Chem. 255, 10,464–10,471.Google Scholar
  122. Yamada T., Kondo A., Takamatsu J., Tateishi J., and Goto I. (1995) Apolipoprotein E mRNA in the brains of patients with Alzheimer’s disease.J. Neurol. Sci. 129, 56–61.PubMedGoogle Scholar
  123. Yankner B. A. (1996) Mechanisms of neuronal degeneration in Alzheimer’s disease.Neuron 16, 921–932.PubMedGoogle Scholar
  124. Zwain I. H., Yen S. S., and Cheng C. Y. (1997) Astrocytes cultured in vitro produce estradiol-17beta and express aromatase cytochrome P-450 (P-450 AROM) mRNA.Biochim. Biophys. Acta. 1334, 338–348.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 1998

Authors and Affiliations

  • Nibaldo C. Inestrosa
    • 1
  • Maria-Paz Marzolo
    • 1
  • Andrea B. Bonnefont
    • 1
  1. 1.Departamento de Biología Celular y Molecular, Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileChile

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