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Inicio Revista Española de Geriatría y Gerontología El péptido β-amiloide: mecanismos de neurotoxicidad. neuroprotección por anti...
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Vol. 36. Núm. 2.
Páginas 109-116 (enero 2001)
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Vol. 36. Núm. 2.
Páginas 109-116 (enero 2001)
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El péptido β-amiloide: mecanismos de neurotoxicidad. neuroprotección por antioxidantes y estrógenos
Amyloid β-peptide: Mechanisms of Neurotoxicity. Neuroprotection by Antioxidants and Estrogens
Visitas
22102
F.J. Muñoz López**
Autor para correspondencia
paco.munoz@cexs.upf.es

Correspondencia: F. J. Muñoz López. Universitat Pompeu Fabra. Dr. Aiguader, 80. 08003 Barcelona. E-mail:
Departament de Cienciès Experimentals i de la Salut. Facultat de Cienciès de la Salut i de la Vida. Universitat Pompeu Fabra. Barcelona
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RESUMEN

La enfermedad de Alzheimer (EA) se caracteriza por la muerte neuronal asociada a la presencia de placas seniles y ovillos neurofibrilares. El componente principal de las placas seniles es el péptido β- amiloide (Aβ) el cual es considerado como un inductor de la neurodegeneración observada en el cerebro de individuos con EA. El objetivo del presente trabajo es revisar el estado actual de la investigación básica sobre los mecanismos de acción neurotóxicos del Aβ, así como el efecto neuroprotector de los estrógenos y de distintos antioxidantes como la vitamina E y la melatonina.

Palabras clave:
β-amiloide
Estrés oxidativo
Antioxidantes
Estrógenos
SUMMARY

The hallmarks of Alzheimer’s disease (AD) are neuronal death, senile plaques and neurofibrillary tangles. Senile plaques are mainly composed of amyloid β-peptide (Aβ) which is considered to trigger the neurodegeneration found in the brains of AD patients. The main goal of the present work is to review the proposed mechanisms which are involved in the Aβ-mediated cytotoxicity and the neuroprotective role of estrogens and antioxidants such as vitamin E and melatonin.

Key words:
β-amyloid
Oxidative stress
Antioxidants
Estrogens
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Bibliografía
[1.]
B. Muller-Hill, K. Beyreuther.
Molecular biology of Alzheimer’s disease.
Annu Rev Biochem, 58 (1989), pp. 287-307
[2.]
R.W. Jacobs, N. Farivar, L.L. Butcher.
Plaque-like lesions in the basal forebrain in Alzheimer’s disease.
Neurosci Lett, 56 (1985), pp. 347-351
[3.]
J. Kang, H.G. Lemaire, A. Unterbeck, J.M. Salbaum, C.L. Masters, K.H. Grzeschik, G. Multhaup, K. Beyreuther, B. Muller-Hill.
The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor.
Nature, 325 (1987), pp. 733-736
[4.]
E.J. Coulson, G.L. Barrett, E. Storey, P.F. Bartlett, K. Beyreuther, C.L. Masters.
Down-regulation of the amyloid protein precursor of Alzheimer’s disease by antisense oligonucleotides reduces neuronal adhesion to specific substrata.
Brain Res, 770 (1997), pp. 72-80
[5.]
T. Saitoh, M. Sundsmo, J.M. Roch, N. Kimura, G. Cole, D. Schubert, et al.
Secreted form of amyloid-b-protein precursor is involved in the growth regulation of fibroblasts.
Cell, 58 (1989), pp. 615-622
[6.]
D.J. Selkoe.
The cell biology of b-amyloid precursor protein and presenilin in Alzheimer’s disease.
Trends Cell Biol, 8 (1998), pp. 447-453
[7.]
K. Duff, C. Eckman, C. Zehr, X. Yu, C.M. Prada, J. Perez-Tur, et al.
Increased amyloid-b42 (43) in brains of mice expressing mutant presenilin 1.
Nature, 383 (1996), pp. 710-713
[8.]
D. Scheuner, C. Eckman, M. Jensen, X. Song, N. Suzuki, T.D. Bird, et al.
Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease.
Nat Med, 2 (1996), pp. 864-870
[9.]
J. Busciglio, D.H. Gabuzda, P. Matsudaira, B.A. Yankner.
Generation of b-amyloid in the secretory pathway in neuronal and nonneuronal cells.
Proc Natl Acad Sci USA, 90 (1993), pp. 2092-2096
[10.]
Y. Luo, T. Sunderland, G.S. Roth, B. Wolozin.
Physiological levels of betaamyloid peptide promote PC12 cell proliferation.
Neurosci Lett, 217 (1996), pp. 125-128
[11.]
C.J. Pike, A.J. Walencewicz, C.G. Glabe, C.W. Cotman.
Aggregation-related toxicity of synthetic beta-amyloid protein in hippocampal cultures.
Eur J Pharmacol, 207 (1991), pp. 367-368
[12.]
N.C. Inestrosa, A. Álvarez, C.A. Pérez, R.D. Moreno, M. Vicente, C. Linker, et al.
Acetylcholinesterase accelerates assembly of amyloid-b-peptides into Alzheimer’s fibrils: possible role of the peripheral site of the enzyme.
Neuron, 16 (1996), pp. 881-891
[13.]
X.D. Cai, T.E. Golde, S.G. Younkin.
Release of excess amyloid b protein from a mutant amyloid b protein precursor.
Science, 259 (1993), pp. 514-516
[14.]
W. Le, W.J. Xie, O. Nyormoi, B.K. Ho, R.G. Smith, S.H. Appel.
beta-Amyloid1- 40 increases expression of beta-amyloid precursor protein in neuronal hybrid cells.
J Neurochem, 65 (1995), pp. 2373-2376
[15.]
J.D. Harper, P.T. Lansbury.
Models of amyloid seeding in Alzheimer’s disease and scrapie: mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins.
Ann Rev Biochem, 66 (1997), pp. 385-407
[16.]
T. Dyrks, E. Dyrks, T. Hartmann, C. Masters, K. Beyreuter.
Amyloidogenicity of bA4 and bA4-bearing amyloid protein precursor fragments by metalcatalyzed oxidation.
J Biol Chem, 267 (1992), pp. 18210-18217
[17.]
T. Oda, P. Wals, H.H. Osterburg, S.A. Johnson, G.M. Pasinetti, T.E. Morgan, et al.
Clusterin (apoJ) alters the aggregation of amyloid beta-peptide (A beta 1-42) and forms slowly sedimenting A beta complexes that cause oxidative stress.
Exp Neurol, 136 (1995), pp. 22-31
[18.]
M.M. Mesulam, C. Geula, M.A. Moran.
Anatomy of cholinesterase inhibition in Alzheimer’s disease: effect of physostigmine and tetrahydroaminoacridine on plaques and tangles.
Ann Neurol, 22 (1987), pp. 683-691
[19.]
P.L. McGeer, T. Kawamata, D.G. Walker.
Distribution of clusterin in Alzheimer brain tissue.
Brain Res, 579 (1992), pp. 337-341
[20.]
A. Alvarez, R. Alarcon, C. Opazo, E.O. Campos, F.J. Muñoz, F.H. Calderon, et al.
Stable complexes involving acetylcholinesterase and amyloid-b peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer’s fibrils.
J Neurosci, 18 (1998), pp. 3213-3223
[21.]
F.J. Muñoz, N.C. Inestrosa.
Neurotoxicity of acetylcholinesterase-amyloid- b-peptide aggregates is dependent on the type of Ab-peptide and the AChE concentration present in the complexes.
FEBS Lett, 450 (1999), pp. 205-209
[22.]
T. Wisniewski, J. Ghiso, B. Frangione.
Peptides homologous to the amyloid protein of Alzheimer’s disease containing a glutamine for glutamic acid substitution have accelerated amyloid fibril formation.
Biochem Biophys Res Commun, 179 (1991), pp. 1247-1254
[23.]
Z. Wang, R. Natte, J.A. Berliner, S.G. van Duinen, H.V. Vinters, W.I. Rosenblum.
Toxicity of Dutch (E22Q) and Flemish (A21G) mutant amyloid b proteins to human cerebral microvessel and aortic smooth muscle cells.
Stroke, 31 (2000), pp. 534-538
[24.]
R. Katzman, R. Terry, R. DeTeresa, T. Brown, P. Davies, P. Fuld, et al.
Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques.
Ann Neurol, 23 (1988), pp. 138-144
[25.]
A.C. McKee, K.S. Kosik, N.W. Kowall.
Neuritic pathology and dementia in Alzheimer’s disease.
Ann Neurol, 30 (1991), pp. 156-165
[26.]
D.J. Selkoe.
Amyloid-b-protein and the genetics of Alzheimer’s disease.
J Biol Chem, 271 (1996), pp. 18295-18298
[27.]
B.J. Cummings, C.J. Pike, R. Shankle, C.W. Cotman.
b-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer’s disease.
Neurobiol Aging, 17 (1996), pp. 921-933
[28.]
Y. Xu, C.R. Jack Jr, P.C. O’Brien, E. Kokmen, G.E. Smith, R.J. Ivnik, et al.
Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD.
Neurology, 54 (2000), pp. 1760-1767
[29.]
W.F. Timmers, F. Tagliavini, J. Haan, B. Frangione.
Parenchymal preamyloid and amyloid deposits in the brains of patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type.
Neurosci Lett, 118 (1990), pp. 223-226
[30.]
R.A. Armstrong.
Factors determining the morphology of b-amyloid deposits in Down’s syndrome.
Neurodegeneration, 4 (1995), pp. 179-186
[31.]
A.M. Schmidt, S.D. Yan, J.L. Wautier, D. Stern.
Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis.
Circ Res, 84 (1999), pp. 489-497
[32.]
S.D. Yan, X. Chen, J. Fu, M. Chen, H. Zhu, A. Roher, et al.
RAGE and amyloid- b peptide neurotoxicity in Alzheimer’s disease.
Nature, 382 (1996), pp. 685-691
[33.]
Y. Liu, R. Dargusch, D. Schubert.
b-amyloid toxicity does not require RAGE protein.
Biochem Biophys Res Commun, 237 (1997), pp. 37-40
[34.]
D.M. Paresce, R.N. Ghosh, F.R. Maxfield.
Microglial cell internalize aggregates of Alzheimer’s disease amyloid b-protein via a scavenger receptor.
Neuron, 17 (1996), pp. 553-565
[35.]
P.L. McGeer, E.G. McGeer.
The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases.
Brain Res Brain Res Rev, 21 (1995), pp. 195-218
[36.]
P.L. McGeer, E.G. McGeer.
Mechanisms of cell death in Alzheimer disease- immunopathology.
J Neural Transm Suppl, 54 (1998), pp. 159-166
[37.]
V.D. Bianca, S. Dusi, E. Bianchini, I. Dal Pra, F. Rossi.
b-amyloid activates the O-2 forming NADPH oxidase in microglia, monocytes, and neutrophils. A possible inflammatory mechanism of neuronal damage in Alzheimer’s disease.
J Biol Chem, 274 (1999), pp. 15493-15499
[38.]
D. Blacker, M.A. Wilcox, N.M. Laird, L. Rodes, S.M. Horvath, R.C. Go, et al.
Alpha-2 macroglobulin is genetically associated with Alzheimer disease.
Nat Genet, 19 (1998), pp. 357-360
[39.]
D.E. Kang, T. Saitoh, X. Chen, Y. Xia, E. Masliah, L.A. Hansen, et al.
Genetic association of the low-density lipoprotein receptor-related protein gene (LRP), an apolipoprotein E receptor, with late-onset Alzheimer’s disease.
Neurology, 49 (1997), pp. 56-61
[40.]
B.V. Zlokovic, C.L. Martel, E. Matsubara, J.G. McComb, G. Zheng, R.T. McCluskey, et al.
Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer’s disease amyloid-b at the blood-brain and blood-cerebrospinal fluid barriers.
Proc Natl Acad Sci USA, 93 (1996), pp. 4229-4234
[41.]
H.Y. Wang, D.H. Lee, M.R. D’Andrea, P.A. Peterson, R.P. Shank, A.B. Reitz.
beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer’s disease pathology.
J Biol Chem, 275 (2000), pp. 5626-5632
[42.]
T. Kihara, S. Shimohama, H. Sawada, J. Kimura, T. Kume, H. Kochiyama, et al.
Nicotinic receptor stimulation protects neurons against b-amyloid toxicity.
Ann Neurol, 42 (1997), pp. 159-163
[43.]
M.R. Zamani, Y.S. Allen, G.P. Owen, J.A. Gray.
Nicotine modulates the neurotoxic effect of b-amyloid protein (25-35) in hippocampal cultures.
Neuroreport, 8 (1997), pp. 513-517
[44.]
E. Perry, C. Martín-Ruiz, M. Lee, M. Griffiths, M. Johnson, M. Piggott, et al.
Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases.
Eur J Pharmacol, 393 (2000), pp. 215-222
[45.]
S. Miranda, C. Opazo, L.F. Larrondo, F.J. Muñoz, F. Ruiz, F. Leighton, N.C. Inestrosa.
The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer’s disease.
Prog Neurobiol, 62 (2000), pp. 633-648
[46.]
M.A. Lovell, W.D. Ehmann, M.P. Mattson, W.R. Markesbery.
Elevated 4-hydroxynonenal in ventricular fluid in Alzheimer’s disease.
Neurobiol Aging, 18 (1997), pp. 457-461
[47.]
R.J. Mark, M.A. Lovell, W.R. Markesbery, K. Uchida, M.P. Mattson.
A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid b-peptide.
J Neurochem, 68 (1997), pp. 255-264
[48.]
M.P. Mattson.
Cellular actions of b-amyloid precursor protein and its soluble and fibrillogenic derivatives.
Physiol Rev, 77 (1997),
[49.]
J.F. Kelly, K. Furukawa, S.W. Barger, M.R. Rengen, R.J. Mark, E.M. Blanc, et al.
Amyloid b-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons.
Proc Natl Acad Sci USA, 93 (1996), pp. 6753-6758
[50.]
R.J. Mark, R. Hensley, D.A. Butterfield, M.P. Mattson.
Amyloid b-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell death.
J Neurosci, 15 (1995), pp. 6239-6249
[51.]
M.P. Mattson, B. Cheng, D. Davis, K. Bryant, I. Lieberburg, R.E. Rydel.
Beta- Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity.
J Neurosci, 12 (1992), pp. 376-389
[52.]
M.A. Smith, G. Perry, P.L. Richey, L.M. Sayre, V.E. Anderson, M.F. Beal, N. Kowall.
Oxidative damage in Alzheimer’s.
Nature, 382 (1996), pp. 120-121
[53.]
A. Nunomura, G. Perry, M.A. Pappolla, R. Wade, K. Hirai, S. Chiba, M.A. Smith.
RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer’s disease.
J Neurosci, 19 (1999), pp. 1959-1964
[54.]
M.A. Lovell, S.P. Gabbita, W.R. Markesbery.
Increased DNA oxidation and decreased levels of repair products in Alzheimer’s disease ventricular CSF.
J Neurochem, 72 (1999), pp. 771-776
[55.]
C. Behl, J. Davis, R. Lesley, D. Schubert.
Hydrogen peroxide mediates amyloid b protein toxicity.
Cell, 77 (1994), pp. 817-827
[56.]
Z. Zhang, R.E. Rydel, C.J. Drzewiecki, K. Fuson, S. Wright, M. Wogulis, et al.
Amyloid b-mediated oxidative and metabolic stress in rat cortical neurons: no direct evidence for a role for H2O2 generation.
J Neurochem, 67 (1996), pp. 1595-1606
[57.]
F.H. Calderón, A. Bonnefont, F.J. Muñoz, V. Fernández, L.A. Videla, N.C. Inestrosa.
PC12 and Neuro 2a cells have different susceptibilities to acetylcholinesterase- amyloid complexes, amyloid 25-35. fragment, glutamate, and hydrogen peroxide.
[58.]
J. Busciglio, B.A. Yankner.
Apoptosis and increased generation of reactive oxygen species in Down’s syndrome neurons in vitro.
Nature, 378 (1995), pp. 776-779
[59.]
C. Behl, J. Davis, G.M. Cole, D. Schubert.
Vitamin E protects nerve cells from amyloid b protein toxicity.
Biochem Biophys Res Commun, 186 (1992), pp. 944-950
[60.]
C. Behl, T. Skutella, F. Lezoualc’h, A. Post, M. Widmann, C.J. Newton, F. Holsboer.
Neuroprotection against oxidative stress by estrogens: structureactivity relationship.
Mol Pharmacol, 51 (1997), pp. 535-541
[61.]
M.A. Pappolla, M. Sos, R.A. Omar, R.J. Bick, D.L. Hickson-Bick, R.J. Reiter, et al.
Melatonin prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide.
J Neurosci, 17 (1997), pp. 1683-1690
[62.]
A.B. Bonnefont, F.J. Muñoz, N.C. Inestrosa.
Estrogen protects neuronal cells from the cytotoxicity induced by acetylcholinesterase-amyloid complexes.
FEBS Lett, 441 (1998), pp. 220-224
[63.]
D.T. Loo, A. Copani, C.J. Pike, E.R. Whittemore, A.J. Walencewicz, C.W. Cotman.
Apoptosis is induced by b-amyloid in cultured central nervous system neurons.
Proc Natl Acad Sci USA, 90 (1993), pp. 7951-7955
[64.]
Q. Guo, B.L. Sopher, K. Furukawa, D.G. Pham, N. Robinson, G.M. Martin, M.P. Mattson.
Alzheimer’s presenilin mutation sensitizes neuronal cells to apoptosis induced by trophic factor withdrawal and amyloid b-peptide: involvement of calcium and oxyradicals.
J Neurosci, 17 (1997), pp. 4212-4222
[65.]
E. Paradis, H. Douillard, M. Koutroumanis, C. Goodyer, A. LeBlanc.
Amyloid- b-peptide of Alzheimer’s disease downregulates Bcl-2 and upregulates bax expression in human neurons.
J Neurosci, 16 (1996), pp. 7533-7539
[66.]
Y. Kitamura, S. Shimohama, T. Ota, Y. Matsuoka, Y. Nomura.
Taniguchi T Alteration of transcription factors NF-kb and STAT1 in Alzheimer’s disease brains.
Neurosci Lett, 237 (1997), pp. 17-20
[67.]
B. Kaltschmidt, M. Uherek, B. Volk, P.A. Baeuerle, C. Kaltschmidt.
Transcription factor NF-kb is activated in primary neurons by amyloid-b-peptides and in neurons surrounding early plaques from patients with Alzheimer’s disease.
Proc Natl Acad Sci USA, 94 (1997), pp. 2642-2647
[68.]
M.A. Smith, R.K. Kutty, P.L. Richey, S.D. Yan, D. Stern, G.J. Chader, et al.
Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer’s disease.
Am J Pathol, 145 (1994), pp. 42-47
[69.]
A. Takeda, T. Kimpara, H. Onodera, Y. Itoyama, S. Shibahara, K. Kogure.
Regional diference in induction of heme oxygenase-1 protein following rat transient forebrain ischemia.
Neurosci Lett, 205 (1996), pp. 169-172
[70.]
L.A. Applegate, P. Luscher, R.M. Tyrrell.
Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells.
Cancer Res, 51 (1991), pp. 974-978
[71.]
M.A. Pappolla, Y.J. Chyan, B. Poeggeler, B. Frangione, G. Wilson, J. Ghiso, R.J. Reiter.
An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer’s disease.
J Neural Transm, 107 (2000), pp. 203-231
[72.]
T. Koppal, R. Subramaniam, J. Drake, M.R. Prasad, H. Dhillon, D.A. Butterfield.
Vitamin E protects against Alzheimer’s amyloid peptide- (25-35) induced changes in neocortical synaptosomal membrane lipid structure and composition.
Brain Res, 786 (1998), pp. 270-273
[73.]
H. Naiki, K. Hasegawa, I. Yamaguchi, H. Nakamura, F. Gejyo, K. Nakakuki.
Apolipoprotein E and antioxidants have different mechanism of inhibiting Alzheimer’s b-amyloid fibril formation in vitro.
Biochemistry, 37 (1998), pp. 17882-17889
[74.]
M. Sano, C. Ernesto, R.G. Thomas, M.R. Klauber, K. Schafer, M. Grundman, et al.
A controlled trial of selegiline, b-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study.
N Engl J Med, 336 (1997), pp. 1216-1222
[75.]
R.J. Reiter, R.C. Carneiro, C.S. Oh.
Melatonin in relation to cellular antioxidative defense mechanisms.
Horm Metab Res, 29 (1997), pp. 363-372
[76.]
C.E. Beyer, J.D. Steketee, D. Saphier.
Antioxidant properties of melatoninan emerging mystery.
Biochem Pharmacol, 56 (1998), pp. 1265-1272
[77.]
R.J. Reiter.
Oxidative damage in the central nervous system: protection by melatonin.
Prog Neurobiol, 56 (1998), pp. 359-384
[78.]
M. Pappolla, P. Bozner, C. Soto, H. Shao, N.K. Robakis, M. Zagorski, et al.
Inhibition of Alzheimer b-fibrillogenesis by melatonin.
J Biol Chem, 273 (1998), pp. 7185-7188
[79.]
M.K. Aronson, W.L. Ooi, H. Morgenstern, A. Hafner, D. Masur, H. Crystal, et al.
Women, myocardial infarction, and dementia in the very old.
Neurology, 40 (1990), pp. 1102-1106
[80.]
M.X. Tang, D. Jacobs, Y. Stern, K. Marder, P. Schofield, B. Gurland, et al.
Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease.
[81.]
R.A. Mulnard, C.W. Cotman, C. Kawas, C.H. van Dyck, M. Sano, R. Doody, et al.
Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer’s Disease Cooperative Study.
JAMA, 283 (2000), pp. 1007-1015
[82.]
B.A. Shaywitz, S.E. Shaywitz.
Estrogen and Alzheimer disease: plausible theory, negative clinical trial.
JAMA, 283 (2000), pp. 1055-1056
[83.]
K. Sugioka, Y. Shimosegawa, M. Nakano.
Estrogen as natural antioxidant of membrane phospholipid peroxidation.
FEBS Lett, 210 (1987), pp. 37-39
[84.]
J.N. Keller, A. Germeyer, J.G. Begley, M.P. Mattson.
17-b-estradiol attenuates oxidative impairment of synaptic Na+/K+-ATPase activity, glucose transport, and glutamate transport induced by amyloid b-peptide and iron.
[85.]
B. Moosmann, C. Behl.
The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties.
Proc Natl Acad Sci USA, 96 (1999),
[86.]
P.S. Green, J. Bishop, J.W. Simpkins.
17 alpha-estradiol exerts neuroprotective effects on SK-N-SH cells.
J Neurosci, 17 (1997), pp. 511-515
[87.]
V.N. Luine.
Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats.
Exp Neurol, 89 (1985), pp. 484-490
[88.]
A.B. Jaffe, C.D. Torand-Allerand, P. Greengard, S.E. Gandy.
Estrogen regulates metabolism of Alzheimer amyloid-b-precursor protein.
J Biol Chem, 269 (1994), pp. 13065-13068
[89.]
H. Xu, G.K. Gouras, J.P. Greenfield, B. Vincent, J. Naslund, L. Mazzarelli, et al.
Estrogen reduces neuronal generation of Alzheimer b-amyloid peptides.
Nat Med, 4 (1998), pp. 447-451
[90.]
G.K. Gouras, H. Xu, R.S. Gross, J.P. Greenfield, B. Hai, R. Wang, P. Greengard.
Testosterone reduces neuronal secretion of Alzheimer’s beta-amyloid peptides.
Proc Natl Acad Sci USA, 97 (2000), pp. 1202-1205
[91.]
A.L. Svensson, A. Nordberg.
Beta-estradiol attenuate amyloid beta-peptide toxicity via nicotinic receptors.
Neuroreport, 10 (1999), pp. 3485-3489
[92.]
H. Honjo, T. Tamura, Y. Matsumoto, M. Kawata, Y. Ogino, K. Tanaka, et al.
Estrogen as a growth factor to central nervous cells. Estrogen treatment promotes development of acetylcholinesterase-positive basal forebrain neurons transplanted in the anterior eye chamber.
J Steroid Biochem Mol Biol, 41 (1992), pp. 633-635
[93.]
R.H. Lustig.
Sex hormone modulation of neural development in vitro.
Horm Behav, 28 (1994), pp. 383-395
[94.]
B.S. McEwen, S.E. Alves, K. Bulloch, N.G. Weiland.
Ovarian steroids and the brain: implications for cognition and aging.
Neurology, 48 (1997), pp. 8-15
[95.]
M. Bobinski, M.J. de Leon, M. Tarnawski, J. Wegiel, B. Reisberg, D.C. Miller, H.M. Wisniewski.
Neuronal and volume loss in CA1 of the hippocampal formation uniquely predicts duration and severity of Alzheimer disease.
Brain Res, 805 (1998), pp. 267-269
[96.]
C.D. Toran-Allerand, R.C. Miranda, W.D. Bentham, F. Sohrabji, T.J. Brown, R.B. Hochberg, N.J. MacLusky.
Estrogen receptors colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain.
Proc Natl Acad Sci USA, 89 (1992), pp. 4668-4672
[97.]
F. Sohrabji, R.C. Miranda, C.D. Toran-Allerand.
Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor.
Proc Natl Acad Sci USA, 92 (1995), pp. 11110-11114
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¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos