Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease

Mota, Sandra I.; Costa, Rui O.; Ferreira, Ildete L.; Santana, Isabel; Caldeira, Gladys L.; Padovano, Carmela; Fonseca, Ana C.; Baldeiras, Inês; Cunha, Catarina; Letra, Liliana; Oliveira, Catarina R.; Pereira, Cláudia M.F.; Rego, Ana Cristina

doi:10.1016/j.bbadis.2015.03.015

Cited by 183Alzheimer's disease research and treatmentsGenomics, phytochemicals, and oxidative stressEndoplasmic Reticulum Stress and Disease

Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease

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Mota, Sandra I., Costa, Rui O., Ferreira, Ildete L., Santana, Isabel, Caldeira, Gladys L., Padovano, Carmela, Fonseca, Ana C., Baldeiras, Inês +5 more·2015·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DOI 10.1016/j.bbadis.2015.03.015

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Abstract

Oxidative stress and endoplasmic reticulum (ER) stress have been associated with Alzheimer's disease (AD) progression. In this study we analyzed whether oxidative stress involving changes in Nrf2 and ER stress may constitute early events in AD pathogenesis by using human peripheral blood cells and an AD transgenic mouse model at different disease stages. Increased oxidative stress and increased phosphorylated Nrf2 (p(Ser40)Nrf2) were observed in human peripheral blood mononuclear cells (PBMCs) isolated from individuals with mild cognitive impairment (MCI). Moreover, we observed impaired ER Ca2+ homeostasis and increased ER stress markers in PBMCs from MCI individuals and mild AD patients. Evidence of early oxidative stress defense mechanisms in AD was substantiated by increased p(Ser40)Nrf2 in 3month-old 3xTg-AD male mice PBMCs, and also with increased nuclear Nrf2 levels in brain cortex. However, SOD1 protein levels were decreased in human MCI PBMCs and in 3xTg-AD mice brain cortex; the latter further correlated with reduced SOD1 mRNA levels. Increased ER stress was also detected in the brain cortex of young female and old male 3xTg-AD mice. We demonstrate oxidative stress and early Nrf2 activation in AD human and mouse models, which fails to regulate some of its targets, leading to repressed expression of antioxidant defenses (e.g., SOD-1), and extending to ER stress. Results suggest markers of prodromal AD linked to oxidative stress associated with Nrf2 activation and ER stress that may be followed in human peripheral blood mononuclear cells.

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Proteasome activity appears to be reduced in Alzheimer disease.
“In fact, proteasome activity seems to be decreased in AD50–52,.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [52]
Section 3.4 mentions the ubiquitin–proteasome pathway as a mechanism for Nrf2 degradation, but does not say its activity is reduced in Alzheimer disease. Searches for decreased proteasome activity and proteasome dysfunction found no passage in our copy addressing that claim; no page number was available. (LLM, conf=0.75)
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Degradation of oxidatively modified proteins remains compromised in Alzheimer disease brain because 20S proteasome activities are dysfunctional, including inhibition by amyloid beta, leading to accumulation of oxidatively modified, often misfolded and dysfunctional proteins.
“Unfortunately, degradation of oxidatively modified proteins is still compromised in AD brain as the 20S proteasome enzymatic activities are dysfunctional51,52 (including inhibition by Aβ), resulting in accumulation of oxidatively modified, often misfolded and dysfunctional proteins.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [52]
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“Mini-mental state”
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
Diagnostic and Statistical Manual of Mental Disorders.
Widiger, T. A. (2000) · Oxford University Press eBooks · doi:10.1037/10518-009 · Cited by 19,767 · see citing works
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634 · see citing works
An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress
Harding, H. P., Zhang, Y., Zeng, H., Novoa, I., Lu, P. D., Calfon, M. A., Sadri, N., Yun, C., Popko, B., Paules, R. S., et al. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00105-9 · Cited by 3,336 · see citing works
Alzheimer’s disease
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69113-7 · Cited by 3,134 · see citing works
Pathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052 · see citing works
Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators
St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.024 · Cited by 2,233 · see citing works
Gadd153 Sensitizes Cells to Endoplasmic Reticulum Stress by Down-Regulating Bcl2 and Perturbing the Cellular Redox State
McCullough, K. D., Martindale, J. L., Klotz, L., Aw, T. Y., & Holbrook, N. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.4.1249-1259.2001 · Cited by 1,895 · see citing works
Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations
Kalyanaraman, B., Darley-Usmar, V. M., Davies, K. J. A., Dennery, P. A., Forman, H. J., Grisham, M. B., Mann, G. E., Moore, K. P., Roberts, L. J., & Ischiropoulos, H. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.09.030 · Cited by 1,795 · see citing works
A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline
Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., et al. (2012) · Nature · doi:10.1038/nature11283 · Cited by 1,738 · see citing works
Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Cycle or a Double-Edged Sword?
Malhotra, J. D., & Kaufman, R. J. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1782 · Cited by 1,555 · see citing works
Nrf2 Is a Direct PERK Substrate and Effector of PERK-Dependent Cell Survival
Cullinan, S. B., Zhang, D. D., Hannink, M., Arvisais, E. W., Kaufman, R. J., & Diehl, J. A. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.20.7198-7209.2003 · Cited by 1,233 · see citing works
Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease
Oddo, S. (2003) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.08.012 · Cited by 980 · see citing works
Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials
Grundman, M. (2004) · Archives of Neurology · doi:10.1001/archneur.61.1.59 · Cited by 972 · see citing works
Aβ Oligomers Induce Neuronal Oxidative Stress through an N-Methyl-D-aspartate Receptor-dependent Mechanism That Is Blocked by the Alzheimer Drug Memantine
De Felice, F. G., Velasco, P. T., Lambert, M. P., Viola, K., Fernandez, S. J., Ferreira, S. T., & Klein, W. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607483200 · Cited by 882 · see citing works
Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment
Scheff, S. W., Price, D. A., Schmitt, F. A., DeKosky, S. T., & Mufson, E. J. (2007) · Neurology · doi:10.1212/01.wnl.0000260698.46517.8f · Cited by 824 · see citing works
Amyloid β-peptide (1-42)-induced Oxidative Stress and Neurotoxicity: Implications for Neurodegeneration in Alzheimer's Disease Brain. A Review
Allan Butterfield, D. (2002) · Free Radical Research · doi:10.1080/1071576021000049890 · Cited by 786 · see citing works
Expression of Nrf2 in Neurodegenerative Diseases
Ramsey, C. P., Glass, C. A., Montgomery, M. B., Lindl, K. A., Ritson, G. P., Chia, L. A., Hamilton, R. L., Chu, C. T., & Jordan-Sciutto, K. L. (2007) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/nen.0b013e31802d6da9 · Cited by 760 · see citing works
Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system - too little activation is bad, too much is even worse
Parsons, C. G., Stöffler, A., & Danysz, W. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.07.013 · Cited by 701 · see citing works
Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure. Report of the MCI Working Group of the European Consortium on Alzheimer's Disease
Portet, F. (2006) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2005.085332 · Cited by 652 · see citing works
Increase of Brain Oxidative Stress in Mild Cognitive Impairment
Praticò, D., Clark, C. M., Liun, F., Lee, V., & Trojanowski, J. Q. (2002) · Archives of Neurology · doi:10.1001/archneur.59.6.972 · Cited by 587 · see citing works
The unfolded protein response
Zhang, K., & Kaufman, R. J. (2006) · Neurology · doi:10.1212/01.wnl.0000192306.98198.ec · Cited by 580 · see citing works
Very Old Women at Highest Risk of Dementia and Alzheimer's Disease: Incidence Data from the Kungsholmen Project, Stockholm
Fratiglioni, L., Viitanen, M., von Strauss, E., Tontodonati, V., Herlitz, A., & Winblad, B. (1997) · Neurology · doi:10.1212/wnl.48.1.132 · Cited by 556 · see citing works
The unfolded protein response is activated in Alzheimer’s disease
Hoozemans, J. J. M., Veerhuis, R., van Haastert, E. S., Rozemüller, A. J. M., Baas, F., Eikelenboom, P., & Scheper, W. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-1038-0 · Cited by 549 · see citing works
Amyloid‐β Deposition in Alzheimer Transgenic Mice Is Associated with Oxidative Stress
Smith, M. A., Hirai, K., Hsiao, K., Pappolla, M. A., Harris, P. L. R., Siedlak, S. L., Tabaton, M., & Perry, G. L. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052212.x · Cited by 547 · see citing works
Phosphorylation of Nrf2 at Ser40 by Protein Kinase C in Response to Antioxidants Leads to the Release of Nrf2 from INrf2, but Is Not Required for Nrf2 Stabilization/Accumulation in the Nucleus and Transcriptional Activation of Antioxidant Response Element-mediated NAD(P)H:Quinone Oxidoreductase-1 Gene Expression
Bloom, D. A., & Jaiswal, A. K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307633200 · Cited by 523 · see citing works
Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice
CHANAS, S. A., JIANG, Q., McMAHON, M., McWALTER, G. K., McLELLAN, L. I., ELCOMBE, C. R., HENDERSON, C. J., WOLF, C. R., MOFFAT, G. J., ITOH, K., et al. (2002) · Biochemical Journal · doi:10.1042/bj20020320 · Cited by 460 · see citing works
The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers
Mattsson, N., Andréasson, U., Persson, S., Arai, H., Batish, S. D., Bernardini, S., Bocchio‐Chiavetto, L., Blankenstein, M. A., Carrillo, M. C., Chalbot, S., et al. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.05.2243 · Cited by 409 · see citing works
A life-course approach to the aetiology of late-onset dementias
Whalley, L. J., Dick, F. D., & McNeill, G. (2005) · The Lancet Neurology · doi:10.1016/s1474-4422(05)70286-6 · Cited by 346 · see citing works
Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease
Resende, R., Moreira, P. I., Proença, T., Deshpande, A., Busciglio, J., Pereira, C., & Oliveira, C. R. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.03.012 · Cited by 343 · see citing works
Self-citation
Amyloid β Peptide of Alzheimer’s Disease Downregulates Bcl-2 and Upregulates Bax Expression in Human Neurons
Paradis, E., Douillard, H., Koutroumanis, M., Goodyer, C. G., & LeBlanc, A. C. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-23-07533.1996 · Cited by 325 · see citing works
Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model
Hirata-Fukae, C., Li, H.-F., Hoe, H.-S., Gray, A. J., Minami, S. S., Hamada, K., Niikura, T., Hua, F., Tsukagoshi-Nagai, H., Horikoshi-Sakuraba, Y., et al. (2008) · Brain Research · doi:10.1016/j.brainres.2008.03.079 · Cited by 284 · see citing works
NMDA Receptor Activation Produces Concurrent Generation of Nitric Oxide and Reactive Oxygen Species: Implications for Cell Death
Gunasekar, P. G., Kanthasamy, A. G., Borowitz, J. L., & Isom, G. E. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65052016.x · Cited by 283 · see citing works
Sex differences in β-amyloid accumulation in 3xTg-AD mice: Role of neonatal sex steroid hormone exposure
Carroll, J. C., Rosario, E. R., Kreimer, S., Villamagna, A., Gentzschein, E., Stanczyk, F. Z., & Pike, C. J. (2010) · Brain Research · doi:10.1016/j.brainres.2010.10.009 · Cited by 273 · see citing works
Intraneuronal amyloid β oligomers cause cell death via endoplasmic reticulum stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo
Umeda, T., Tomiyama, T., Sakama, N., Tanaka, S., Lambert, M. P., Klein, W. L., & Mori, H. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22640 · Cited by 264 · see citing works
Neurotoxic effect of oligomeric and fibrillar species of amyloid-beta peptide 1-42: Involvement of endoplasmic reticulum calcium release in oligomer-induced cell death
Resende, R., Ferreiro, E., Pereira, C., & Resende de Oliveira, C. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.06.036 · Cited by 235 · see citing works
Self-citation
The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway
Ferreiro, E. B., Oliveira, C. R., & Pereira, C. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.02.003 · Cited by 219 · see citing works
Self-citation
An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity
Ferreiro, E. B., Resende, R., Costa, R. O., Oliveira, C. R., & Pereira, C. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.05.011 · Cited by 199 · see citing works
Self-citation
Amyloid beta peptide 1–42 disturbs intracellular calcium homeostasis through activation of GluN2B-containing N-methyl-d-aspartate receptors in cortical cultures
Ferreira, I. L., Bajouco, M., Mota, S. I., Auberson, Y. P., Oliveira, C. R., & Rego, A. C. (2011) · Cell Calcium · doi:10.1016/j.ceca.2011.11.008 · Cited by 185 · see citing works
Self-citation
Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer's Disease (AD) individuals
Lombardi, V., Garcı́a, M., Rey, L., & Cacabelos, R. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00046-6 · Cited by 182 · see citing works
Multiple Defects in Energy Metabolism in Alzheimers Disease
Ferreira, I. L., Resende, R., Ferreiro, E. B., Rego, A. C., & Pereira, C. (2010) · Current Drug Targets · doi:10.2174/1389450111007011193 · Cited by 177 · see citing works
Self-citation
Activation of mammalian IRE1α upon ER stress depends on dissociation of BiP rather than on direct interaction with unfolded proteins
Oikawa, D., Kimata, Y., Kohno, K., et al. (2009) · Experimental Cell Research · doi:10.1016/j.yexcr.2009.06.009 · Cited by 176 · see citing works
Integration of the Unfolded Protein and Oxidative Stress Responses through SKN-1/Nrf
Glover-Cutter, K. M., Lin, S., & Blackwell, T. K. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003701 · Cited by 175 · see citing works
Oxidative damage to DNA in lymphocytes from AD patients
Mecocci, P., Polidori, M. C., Ingegni, T., Cherubini, A., Chionne, F., Cecchetti, R., & Senin, U. (1998) · Neurology · doi:10.1212/wnl.51.4.1014 · Cited by 166 · see citing works
Peripheral Oxidative Damage in Mild Cognitive Impairment and Mild Alzheimer's Disease
Baldeiras, I., Santana, I. J., Proença, M. T., Garrucho, M. H., Pascoal, R., Rodrigues, A. P., Duro, D., & Oliveira, C. R. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-15110 · Cited by 157 · see citing works
Self-citation
Increased production of inflammatory cytokines in mild cognitive impairment
Magaki, S., Mueller, C., DICKSON, C., & Kirsch, W. M. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.09.015 · Cited by 156 · see citing works
Mitochondrial- and Endoplasmic Reticulum-Associated Oxidative Stress in Alzheimer's Disease: From Pathogenesis to Biomarkers
Ferreiro, E. B., Baldeiras, I., Ferreira, I. L., Costa, R. O., Rego, A. C., Pereira, C., & Oliveira, C. R. (2012) · International Journal of Cell Biology · doi:10.1155/2012/735206 · Cited by 152 · see citing works
Self-citation
Single-day apolipoprotein E genotyping
Crook, R., Hardy, J., & Duff, K. (1994) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(94)90168-6 · Cited by 149 · see citing works
Use of thapsigargin to study Ca2+ homeostasis in cardiac cells
Rogers, T. B., Inesi, G., Wade, R., & Lederer, W. J. (1995) · Bioscience Reports · doi:10.1007/bf01788366 · Cited by 147 · see citing works
Oxidative Stress, Perturbed Calcium Homeostasis, and Immune Dysfunction in Alzheimer's Disease
Mattson, M. P. (2002) · Journal of NeuroVirology · doi:10.1080/13550280290100978 · Cited by 142 · see citing works
Mild oxidative stress activates Nrf2 in astrocytes, which contributes to neuroprotective ischemic preconditioning
Bell, K. F., Al-Mubarak, B., Fowler, J. H., Baxter, P. S., Gupta, K., Tsujita, T., Chowdhry, S., Patani, R., Chandran, S., Horsburgh, K., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015229108 · Cited by 133 · see citing works
In vivo cellular adaptation to ER stress: survival strategies with double-edged consequences
Tsang, K. Y., Chan, D. T.-M., Bateman, J. F., & Cheah, K. S. E. (2010) · Journal of Cell Science · doi:10.1242/jcs.068833 · Cited by 129 · see citing works
Overexpressed cyclophilin B suppresses apoptosis associated with ROS and Ca2+ homeostasis after ER stress
Kim, J., Choi, T. G., Ding, Y., Kim, Y., Ha, K., Lee, K. H., Kang, I., Ha, J., Kaufman, R. J., Lee, J., et al. (2008) · Journal of Cell Science · doi:10.1242/jcs.028654 · Cited by 116 · see citing works
Glutamate Toxicity on a PC12 Cell Line Involves Glutathione (GSH) Depletion and Oxidative Stress
Pereira, C., & Oliveira, C. R. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00020-8 · Cited by 115 · see citing works
Self-citation
Endoplasmic reticulum stress occurs downstream of GluN2B subunit ofN‐methyl‐D‐aspartate receptor in mature hippocampal cultures treated with amyloid‐β oligomers
Costa, R. O., Lacor, P. N., Ferreira, I. L., Resende, R., Auberson, Y. P., Klein, W. L., Oliveira, C. R., Rego, A. C., & Pereira, C. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00848.x · Cited by 109 · see citing works
Self-citation
The trascriptional activation of the human copper/zinc superoxide dismutase gene by 2,3,7,8-tetrachlorodibenzo-p-dioxin through two different regulator sites, the anitoxidant responsive element and xenobiotic responsive element
Park, E. Y., & Rho, H. M. (2002) · Molecular and Cellular Biochemistry · doi:10.1023/a:1020600509965 · Cited by 107 · see citing works
Elevated levels of oxidative DNA damage in lymphocytes from patients with Alzheimer’s disease11Abbreviations used: AD, Alzheimer’s disease; Endo III, Endonuclease III; 8OHA, 8-hydroxyadenine; 8OHG, 8-hydroxyguanine; 8OHdG, 8-hydroxy-2′-deoxyguanosine; Fapy-Ade, 4,6-diamino-5-formamidopyrimidine; Fapy-Gua, 2,6,-diamino-4-hydroxy-5-formamidopyrimidine; Fpg, formamidopyrimidine glycosilase; H2O2, hydrogen-peroxide; .OH, hydroxyl radical; PBS, phosphate-buffered saline; ROS, reactive oxygen species; RT, room temperature; SSB, single strand break
Mórocz, M., Kalman, J. L., Juhász, A., Sinkó, I., McGlynn, A. P., Downes, C. S., Janka, Z., & Raskó, I. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00257-3 · Cited by 105 · see citing works
The effects of 90-day supplementation with the Omega-3 essential fatty acid docosahexaenoic acid (DHA) on cognitive function and visual acuity in a healthy aging population
Stough, C. K. K., Downey, L. A., Silber, B. Y., Lloyd, J., Kure, C., Wesnes, K. A., & Camfield, D. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.03.019 · Cited by 97 · see citing works
Aβ and NMDAR activation cause mitochondrial dysfunction involving ER calcium release
Ferreira, I. L., Ferreiro, E. B., Schmidt, J., Cardoso, J. M. R., Pereira, C., Carvalho, A. L., Oliveira, C. R., & Rego, A. C. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.09.006 · Cited by 97 · see citing works
Self-citation
NADPH oxidase activity is essential for Keap1/Nrf2-mediated induction of GCLC in response to 2-indol-3-yl-methylenequinuclidin-3-ols.
Sekhar, K. R., Crooks, P. A., Sonar, V. N., Friedman, D. B., Chan, J. Y., Meredith, M. J., Starnes, J. H., Kelton, K. R., Summar, S. R., Sasi, S., et al. (2003) · PubMed · Cited by 96 · see citing works
Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease
Marchese, M., Cowan, D., Head, E., Ma, D., Karimi, K., Ashthorpe, V., Kapadia, M., Zhao, H., Davis, P., & Sakic, B. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-131490 · Cited by 94 · see citing works
The unfolded protein response and proteostasis in Alzheimer disease
Scheper, W., Nijholt, D. A. T., & Hoozemans, J. J. M. (2011) · Autophagy · doi:10.4161/auto.7.8.15761 · Cited by 92 · see citing works
Oxidative Damage and Progression to Alzheimer's Disease in Patients with Mild Cognitive Impairment
Baldeiras, I., Santana, I. J., Proença, M. T., Garrucho, M. H., Pascoal, R., Rodrigues, A. P., Duro, D., & Oliveira, C. R. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-091723 · Cited by 88 · see citing works
Self-citation
Epigenetic regulation of BACE1 in Alzheimer’s disease patients and in transgenic mice
Marques, S., Lemos, R., Ferreiro, E. B., Martins, M., de Mendonça, A., Santana, I. J., Outeiro, T. F., & Pereira, C. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.06.029 · Cited by 81 · see citing works
Self-citation
Amyloid β-induced ER stress is enhanced under mitochondrial dysfunction conditions
Costa, R. O., Ferreiro, E. B., Martins, I., Santana, I. J., Cardoso, S. M., Oliveira, C. R., & Pereira, C. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.04.011 · Cited by 76 · see citing works
Self-citation
Enhanced apoptosis, oxidative stress and mitochondrial dysfunction in lymphocytes as potential biomarkers for Alzheimer’s disease
Leuner, K., Pantel, J., Frey, C., Schindowski, K., Schulz, K. L., Wegat, T., Maurer, K., Eckert, A., & Müller, W. E. G. (2007) · Springer eBooks · doi:10.1007/978-3-211-73574-9_27 · Cited by 74 · see citing works
Impaired Transcription in Alzheimer's Disease: Key Role in Mitochondrial Dysfunction and Oxidative Stress
Caldeira, G. L., Ferreira, I. L., & Rego, A. C. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-121444 · Cited by 70 · see citing works
Self-citation
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Kanninen, K. M., White, A. R., Koıstınaho, J., & Malm, T. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/985085 · Cited by 68 · see citing works
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Huang, H., Ou, H., & Hsieh, S. (2000) · Life Sciences · doi:10.1016/s0024-3205(00)00511-7 · Cited by 61 · see citing works
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Pino, S. C., O’Sullivan-Murphy, B., Lidstone, E. A., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005468 · Cited by 57 · see citing works
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Mashkina, A. P., Čı́žková, D., Vanický, I., & Болдырев, А. А. (2010) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-010-9519-7 · Cited by 51 · see citing works
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Chen, M., Wu, S., Tsai, T., Wang, L., & Tsai, F. (2013) · Immunopharmacology and Immunotoxicology · doi:10.3109/08923973.2013.828744 · Cited by 50 · see citing works
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Yoshida, H. (2009) · IUBMB Life · doi:10.1002/iub.229 · Cited by 49 · see citing works
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Adunsky, A., Baram, D., Hershkowitz, M., et al. (1991) · Journal of Neuroimmunology · doi:10.1016/0165-5728(91)90060-k · Cited by 48 · see citing works
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Tacconi, S., Perri, R., Balestrieri, E., Grelli, S., Bernardini, S., Annichiarico, R., Mastino, A., Caltagirone, C., & Macchi, B. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.07.009 · Cited by 44 · see citing works
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Umeda, T., Tomiyama, T., Sakama, N., Tanaka, S., Lambert, M., Klein, W., & Mori, H. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.05.1574 · Cited by 41 · see citing works
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Ha, J. S., Lee, J. E., Lee, J.-R., Lee, C.-S., Maeng, J.-S., Bae, Y. S., Kwon, K., & Park, S. S. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.03.021 · Cited by 41 · see citing works
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Dragunow, M. (2004) · Frontiers in bioscience · doi:10.2741/1197 · Cited by 40 · see citing works
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Bonomo, S., Rigamonti, A. E., Giunta, M., Galimberti, D., Guaita, A., Gagliano, M. G., Müller, E. E., & Cella, S. G. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.05.017 · Cited by 39 · see citing works
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Tagashira, H., Bhuiyan, M. S., & Fukunaga, K. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00300.2013 · Cited by 38 · see citing works
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Schapansky, J., Olson, K. L., der Ploeg, R. V., & Glazner, G. W. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.04.009 · Cited by 35 · see citing works
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Costa, R. O., Ferreiro, E. B., Oliveira, C. R., & Pereira, C. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.09.005 · Cited by 34 · see citing works
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Eckert, A., Oster, M., Zerfass, R., Hennerici, M. G., & Müller, W. E. (2001) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000051242 · Cited by 32 · see citing works
Alterations of intracellular calcium regulation during aging and Alzheimer's disease in nonneuronal cells
Eckert, A., Hartmann, H., Förstl, H., et al. (1994) · Life Sciences · doi:10.1016/0024-3205(94)00382-3 · Cited by 31 · see citing works
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Violi, F., & Pignatelli, P. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5527 · Cited by 18 · see citing works
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Eckert, A., Förstl, H., Zerfaß, R., et al. (1998) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-7508-8_20 · Cited by 9 · see citing works

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Authors: Mota, S. I., Costa, R. O., Ferreira, I. L., Santana, I., Caldeira, G. L., Padovano, C., Fonseca, A. C., Baldeiras, I., Cunha, C., Letra, L., Oliveira, C. R., Pereira, C. M. F., & Rego, A. C.
Affiliations: Centro de Neurociências e Biologia Celular (PT)
Unidade Local de Saúde de Coimbra (PT)
Corresponding author: Pereira, Cláudia M.F.
Rego, Ana Cristina
ORCID: Mota, Sandra I.
Costa, Rui O.
Ferreira, Ildete L.
Santana, Isabel
Caldeira, Gladys L.
Padovano, Carmela
Fonseca, Ana C.
Baldeiras, Inês
Cunha, Catarina
Letra, Liliana
Oliveira, Catarina R.
Pereira, Cláudia M.F.
Rego, Ana Cristina
Venue: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher: Elsevier BV
Published: 2015-07
Volume: 1852
Issue: 7
Pages: 1428-1441
ISSN: 0925-4439 (ISSN-L)
DOI: 10.1016/j.bbadis.2015.03.015
OpenAlex: W2094185904
Cited by: 183
References: 92
Citations by year: 2026: 6 · 2025: 12 · 2024: 14 · 2023: 8 · 2022: 12 · 2021: 22 · 2020: 22 · 2019: 23 · 2018: 17 · 2017: 22 · 2016: 19 · 2015: 5
FWCI: 15.50
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 366 d)
Locations: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
PubMed (publishedVersion)
Funders: QREN Diamarker "Desenvolvimento e Operacionalização da Investigação de Translação (DOIT)
Lundbeck Foundation
"Fundação para a Ciência e a Tecnologia (FCT), Portugal, (PEst-C/SAU/LA0001/2013-2014, SFRH/BD/43430/2008, SFRH/BPD/99219/2013, SFRH/BD/28403/2006, SFRH/BD/47573/2008)
FEDER
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords: Alzheimer's disease, oxidative stress, Nrf2, endoplasmic reticulum stress, mild cognitive impairment, peripheral blood mononuclear cells, 3xTg-AD mice, SOD1, ER calcium homeostasis, antioxidant defense, prodromal Alzheimer's disease, cerebral cortex
MeSH terms: Superoxide Dismutase-1, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Cells, Cultured, Cerebral Cortex, Female, Humans, Male, Mice, Inbred C57BL, Middle Aged, RNA, Messenger, Superoxide Dismutase, Oxidative Stress, NF-E2-Related Factor 2, Mice, Endoplasmic Reticulum Stress, Cognitive Dysfunction

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Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease

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