Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease

Cioffi, Federica; Adam, Rayan Hassan Ibrahim; Broersen, Kerensa

doi:10.3233/jad-190863

Cited by 204Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchRedox biology and oxidative stress

Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease

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Cioffi, Federica, Adam, Rayan Hassan Ibrahim, Broersen, Kerensa·2019·Journal of Alzheimer s Disease

DOI 10.3233/jad-190863PMC PMC6971833

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Abstract

Alzheimer's disease is the most common neurodegenerative disorder that can cause dementia in elderly over 60 years of age. One of the disease hallmarks is oxidative stress which interconnects with other processes such as amyloid-β deposition, tau hyperphosphorylation, and tangle formation. This review discusses current thoughts on molecular mechanisms that may relate oxidative stress to Alzheimer's disease and identifies genetic factors observed from in vitro, in vivo, and clinical studies that may be associated with Alzheimer's disease-related oxidative stress.

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Oxidative damage has been implicated in all major neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis.
“Oxidative damage has been implicated in all major neurodegenerative diseases including Alzheimer’s disease (AD) [108,109], Parkinson’s disease (PD) [110,111], Huntington’s disease (HD) [112,113], amyotrophic lateral sclerosis (ALS) [114], and multiple sclerosis (MS) [115].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [109]

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Background
BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis
Rudic, R. D., McNamara, P., Curtis, A.-M., Boston, R. C., Panda, S., Hogenesch, J. B., & FitzGerald, G. A. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020377 · Cited by 1,059 · see citing works
Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors
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“Both SirT3 and BMAL1 levels are tightly regulated by circadian rhythmicity of oxidoreductase factor nicotinamide adenine dinucleotide (NAD+) [342], while, in turn cellular redox status affects the activity of clock transcription factors [335].”
Background
4‐Hydroxynonenal‐Derived Advanced Lipid Peroxidation End Products Are Increased in Alzheimer's Disease
Sayre, L., Zelasko, D. A., Harris, P. L. R., Perry, G., Salomon, R. G., & Smith, M. A. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68052092.x · Cited by 1,032 · see citing works
Dramatic Aggregation of Alzheimer Aβ by Cu(II) Is Induced by Conditions Representing Physiological Acidosis
Atwood, C. S., Moir, R. D., Huang, X., Scarpa, R. C., Bacarra, N. M. E., Romano, D. M., Hartshorn, M. A., Tanzi, R. E., & Bush, A. I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.12817 · Cited by 1,009 · see citing works
Melatonin: an ancient molecule that makes oxygen metabolically tolerable
Manchester, L. C., Coto‐Montes, A. M., Boga, J. A., Andersen, L. P. H., Zhou, Z., Galano, A., Vriend, J. P., Tan, D. X., & Reiter, R. J. (2015) · Journal of Pineal Research · doi:10.1111/jpi.12267 · Cited by 954 · cited 1× · see citing works
“antioxidant activity, either directly by scavenging a 621 variety of free radicals including hydroxyl, peroxyl, 622 superoxide, peroxide and peroxynitrite (ONOO−) 623 [141, 142], or indirectly by inducing antioxidant 624”
Background
Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease
Yao, J., Irwin, R. W., Zhao, L., Nilsen, J., Hamilton, R. T., & Brinton, R. D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903563106 · Cited by 940 · cited 1× · see citing works
“Related to this, pre-symptomatic AD has been associated with mitochondrial deficiency resulting in disturbed bioenergetics [8].”
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Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease
Bezprozvanny, I., & Mattson, M. P. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.06.005 · Cited by 938 · cited 1× · see citing works
“Release of Ca2+ from the extracellular pools into the cell is mediated by factors such as voltage-gated Ca2+ channels, N-methylo-Daspartate (NMDA) receptors and transient receptor potential channels while intracellular Ca2+, stored in the endoplasmic reticulum, is released via the inositol triphosphate receptor (Ins[1…”
Background
Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease
Du, H., Guo, L., Fang, F., Chen, D., Sosunov, A. A., McKhann, G. M., Yan, Y., Wang, C., Zhang, H., Molkentin, J. D., et al. (2008) · Nature Medicine · doi:10.1038/nm.1868 · Cited by 935 · see citing works
Advanced Glycosylation End Products in Patients with Diabetic Nephropathy
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“AGEs are the product of non-enzymatic aldose-mediated glycated or oxidized proteins [422], and accumulation of AGEs was shown to be agingrelated [423, 424] and accelerates in conditions such as diabetes [425].”
Background
Peroxiredoxins are conserved markers of circadian rhythms
Edgar, R. S., Green, E. W., Zhao, Y., Gerben Van Ooijen, A., Olmedo, M., Qin, X., Xu, Y. Q., Pan, M., Valekunja, U. K., Feeney, K. A., et al. (2012) · Nature · doi:10.1038/nature11088 · Cited by 915 · cited 1× · see citing works
“On the other hand, brain and peripheral tissues were shown to differ in their peroxiredoxin oxidation rhythms [324] as well as in other clock components [325].”
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Apolipoprotein E allele–specific antioxidant activity and effects on cytotoxicity by oxidative insults and β–amyloid peptides
Miyata, M., & Smith, J. D. (1996) · Nature Genetics · doi:10.1038/ng0996-55 · Cited by 889 · cited 1× · see citing works
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Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress
Stamer, K., Vogel, R., Thies, E., Mandelkow, E., & Mandelkow, E.-M. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200108057 · Cited by 885 · cited 23× · see citing works
“In another study, methionine 35 of synthesized A 1-42 was oxidized by exposure to H2O2 and oxidation was validated using mass spectrometry.”
BackgroundInfluential
Effect of cadmium on lipid peroxidation, superoxide anion generation and activities of antioxidant enzymes in growing rice seedlings
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“These ROS, in turn, have been related to membrane damage, cytoskeletal alterations, and cell death [9].”
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Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments
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Glutathione and Related γ-Glutamyl Compounds: Biosynthesis and Utilization
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BackgroundInfluential
Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage
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“Further, AD mouse models and AD patients show the presence of multiple small mitochondria and exaggerated mitochondrial division [120] suggesting that the mitochondrial fission process is altered in AD.”
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The Transcriptional Activity of NF-κB Is Regulated by the IκB-Associated PKAc Subunit through a Cyclic AMP–Independent Mechanism
Zhong, H., Suyang, H., Erdjument‐Bromage, H., Tempst, P., & Ghosh, S. (1997) · Cell · doi:10.1016/s0092-8674(00)80222-6 · Cited by 828 · see citing works
Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia
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Properties of the Permeability Transition Pore in Mitochondria Devoid of Cyclophilin D
Basso, E., Fante, L., Fowlkes, J., Petronilli, V., Forte, M. A., & Bernardi, P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500089200 · Cited by 808 · see citing works
Advanced glycation end products contribute to amyloidosis in Alzheimer disease
Vitek, M. P., Bhattacharya, K., Glendening, J. M., Stopa, E., Vlassara, H., Bucala, R., Manogue, K., & Cerami, A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.11.4766 · Cited by 806 · see citing works
Coordinate Regulation of Glutathione Biosynthesis and Release by Nrf2-Expressing Glia Potently Protects Neurons from Oxidative Stress
Shih, A. Y., Johnson, D. A., Wong, G., Kraft, A. D., Jiang, L., Erb, H., Johnson, J. A., & Murphy, T. H. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03394.2003 · Cited by 786 · see citing works
Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues.
Brett, J., Schmidt, A. M., Yan, S. D., Zou, Y. S., Weidman, E., Pinsky, D. J., Nowygrod, R., Neeper, M. P., Przysiecki, C. T., & SHAW, A. R. (1993) · PubMed Central · Cited by 776 · see citing works
Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid
Suh, J. H., Shenvi, S. V., Dixon, B. M., Liu, H., Jaiswal, A. K., Liu, R.-M., & Hagen, T. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400282101 · Cited by 774 · see citing works
apoE isoform–specific disruption of amyloid β peptide clearance from mouse brain
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“The pathogenic origins of ApoE4 have been studied to great length and indicate that ApoE4 is involved in processes such as aggregation and clearance of A [240, 241], mitochondrial dysfunction, and impairment of calcium [242, 243] or cellular iron homeostasis [244], and ApoE4 affects synaptic architecture and functioni…”
Background
RNA Oxidation Is a Prominent Feature of Vulnerable Neurons in Alzheimer’s Disease
Nunomura, A., Perry, G., Pappolla, M., Wade, R., Hirai, K., Chiba, S., & Smith, M. A. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-06-01959.1999 · Cited by 768 · cited 1× · see citing works
“brain tissues of patients affected by AD [36].”
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Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain
Mecocci, P., MacGarvey, U., Kaufman, A. E., Koontz, D., Shoffner, J. M., Wallace, D. C., & Beal, M. F. (1993) · Annals of Neurology · doi:10.1002/ana.410340416 · Cited by 757 · see citing works
Mitochondria Are Excitable Organelles Capable of Generating and Conveying Electrical and Calcium Signals
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Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease
Frölich, L., Blum-Degen, D., Bernstein, H.-G., Engelsberger, S., Humrich, J., Laufer, S., Muschner, D., Thalheimer, A., Türk, A., Hoyer, S., et al. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050068 · Cited by 748 · cited 1× · see citing works
“1676 Upon aging, glucose metabolism derails progres1677 sively as a result of changes in brain insulin [404], 1678 and cortisol [405] levels.”
Background
Sleep Quality and Preclinical Alzheimer Disease
Ju, Y.-E. S., McLeland, J. S., Toedebusch, C. D., Xiong, C., Fagan, A. M., Duntley, S. P., Morris, J. C., & Holtzman, D. M. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.2334 · Cited by 744 · see citing works
Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro
Busciglio, J., & Yankner, B. A. (1995) · Nature · doi:10.1038/378776a0 · Cited by 741 · cited 1× · see citing works
“Programmed cell death could be rescued by administration of free radical scavengers including vitamin E, and N-tert-butyl-2sulphophenylnitrone [263] but dietary parameters did not alleviate oxidative stress biomarkers in young adult DS patients [20].”
Background
beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease.
Roher, A. E., Lowenson, J. D., Clarke, S., Woods, A. S., Cotter, R. J., Gowing, E., & Ball, M. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10836 · Cited by 740 · see citing works
The Role of Amyloid-β Oligomers in Toxicity, Propagation, and Immunotherapy
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The cellular response to oxidative stress: influences of mitogen-activated protein kinase signalling pathways on cell survival
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“More1249 over, members of the SAPK family were also found to 1250 be upregulated in AD patient brains [30, 313] and are 1251 activated by various stress signals including oxida1252 tive stress [314, 315].”
Background
Mitochondrial dysfunction is a trigger of Alzheimer's disease pathophysiology
Moreira, P. I., Carvalho, C., Zhu, X., Smith, M. A., & Perry, G. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.10.006 · Cited by 734 · see citing works
Mitochondrial DNA Damage and Dysfunction Associated With Oxidative Stress in Failing Hearts After Myocardial Infarction
Ide, T., Tsutsui, H., Hayashidani, S., Kang, D., Suematsu, N., Nakamura, K., Utsumi, H., Hamasaki, N., & Takeshita, A. (2001) · Circulation Research · doi:10.1161/01.res.88.5.529 · Cited by 733 · cited 1× · see citing works
“myocardial infarction [18], sickle cell disease [19],”
Regulation of hypoxia-inducible factor-1α by NF-κB
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“NF-kB has been identified as important regulator of HIF-1 expression [295].”
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Elevated β-secretase expression and enzymatic activity detected in sporadic Alzheimer disease
Yang, L.-B., Lindholm, K., Yan, R., Citron, M., Xia, W., Yang, X.-L., Beach, T., Sue, L., Wong, P., Price, D., et al. (2003) · Nature Medicine · doi:10.1038/nm0103-3 · Cited by 729 · cited 1× · see citing works
“P38MAPK was also reported to be active and identified in A deposits of A PP tg mice [310].”
Background
Regulation of Oxidative Stress by the Anti-aging Hormone Klotho*♦
Yamamoto, M., Clark, J. D., Pastor, J. V., Gurnani, P., Nandi, A., Kurosu, H., Miyoshi, M., Ogawa, Y., Castrillón, D. H., Rosenblatt, K. P., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509039200 · Cited by 724 · cited 5× · see citing works
“NAD+-dependent deacetylase SirT3 is an important regulator of energy production and redox response by reduction of GSH [331, 332], mediating the upregulation of SOD2 and catalase [333], and activation of SOD2 [334].”
BackgroundResultInfluential
β-Secretase Protein and Activity Are Increased in the Neocortex in Alzheimer Disease
Fukumoto, H. (2002) · Archives of Neurology · doi:10.1001/archneur.59.9.1381 · Cited by 695 · see citing works
Presenilins Form ER Ca2+ Leak Channels, a Function Disrupted by Familial Alzheimer's Disease-Linked Mutations
Tu, H., Nelson, O. L., Bezprozvanny, A., Wang, Z., Lee, S.-F., Hao, Y.-H., Serneels, L., Strooper, B. D., Yu, G., & Борисович, Б. И. (2006) · Cell · doi:10.1016/j.cell.2006.06.059 · Cited by 691 · cited 1× · see citing works
“For example, whereas wild type presenilin was reported to form Ca2+ permeable channels allowing Ca2+ leakage from the endoplasmic reticulum [438, 439], some, but not all FAD related mutations in Psen1 and 2, show deficiencies in Ca2+ leak function in a mouse embryonic fibroblast model, primary fibroblasts obtained fro…”
Background
Oxidative stress in brain aging, neurodegenerative and vascular diseases: An overview
Mariani, E., Polidori, M. C., Cherubini, A., & Mecocci, P. (2005) · Journal of Chromatography B · doi:10.1016/j.jchromb.2005.04.023 · Cited by 682 · see citing works
Toward clinical application of the Keap1-Nrf2 pathway
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Identification of the HumanKlothoGene and Its Two Transcripts Encoding Membrane and SecretedKlothoProtein
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Transient and Long-Lasting Openings of the Mitochondrial Permeability Transition Pore Can Be Monitored Directly in Intact Cells by Changes in Mitochondrial Calcein Fluorescence
Petronilli, V., Miotto, G., Canton, M., Brini, M., Colonna, R., Bernardi, P., & Lisa, F. D. (1999) · Biophysical Journal · doi:10.1016/s0006-3495(99)77239-5 · Cited by 677 · see citing works
Antioxidative Protection by Melatonin: Multiplicity of Mechanisms from Radical Detoxification to Radical Avoidance
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Circadian Clock NAD + Cycle Drives Mitochondrial Oxidative Metabolism in Mice
Peek, C. B., Affinati, A. H., Ramsey, K. M., Kuo, H.-Y., Yu, W., Sena, L. A., Ilkayeva, O., Marcheva, B., Kobayashi, Y., Omura, C., et al. (2013) · Science · doi:10.1126/science.1243417 · Cited by 658 · see citing works
Modulation of transcription factor NF-kappa B binding activity by oxidation-reduction in vitro.
Toledano, M. B., & Leonard, W. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.10.4328 · Cited by 657 · cited 6× · see citing works
“cation of NFκB [180], and, as such, ROS was found”
BackgroundInfluential
Effect of Lipid Peroxidation on the Properties of Lipid Bilayers: A Molecular Dynamics Study
Wong-ekkabut, J., Xu, Z., Triampo, W., Tang, I., Tieleman, D. P., & Monticelli, L. (2007) · Biophysical Journal · doi:10.1529/biophysj.107.112565 · Cited by 645 · see citing works
Characterization of Copper Interactions with Alzheimer Amyloid β Peptides: Identification of an Attomolar‐Affinity Copper Binding Site on Amyloid β1‐42
Atwood, C. S., Scarpa, R. C., Huang, X., Moir, R. D., Jones, W. D., Fairlie, D. P., Tanzi, R. E., & Bush, A. I. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0751219.x · Cited by 641 · see citing works
Alterations in the circadian rest-activity rhythm in aging and Alzheimer's disease
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Aβ plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks
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“6 packaged into an adeno-associated virus (AAV2) and expressed in the brains of adult transgenic APP/PS1 mice showed that calcium overloaded neurites in living animals were more likely to be located in close proximity (<25 m) of a plaque [175].”
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The neurobiology of glia in the context of water and ion homeostasis
Simard, M. F., & Nedergaard, M. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.09.053 · Cited by 607 · cited 1× · see citing works
“which subsequently binds to purine receptors on 1864 the membrane of adjacent astrocytes [441].”
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Oxidative stress in the progression of Alzheimer disease in the frontal cortex
Ansari, M. A., & Scheff, S. W. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181cb5af4 · Cited by 605 · cited 2× · see citing works
“corroborates the thought that oxidative stress is an 799 early stage pathological feature of AD [188].”
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A signalling role for 4‐hydroxy‐2‐nonenal in regulation of mitochondrial uncoupling
Echtay, K. S., Esteves, T. C., Pakay, J. L., Jekabsons, M. B., Lambert, A. J., Portero‐Otín, M., Pamplona, R., Vidal‐Puig, A. J., Wang, S., Roebuck, S. J., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg412 · Cited by 597 · cited 1× · see citing works
“Interestingly, HNE levels were observed to be proportional to the extent of neuronal lesions [28, 29].”
Background
Oxidative Stress, Thiol Reagents, and Membrane Potential Modulate the Mitochondrial Permeability Transition by Affecting Nucleotide Binding to the Adenine Nucleotide Translocase
Halestrap, A. P., Woodfield, K.-Y., & Connern, C. P. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3346 · Cited by 592 · cited 1× · see citing works
“models have shown that mPTP formation can be efficiently blocked by the addition of a cyclophilin D inhibitor, cyclosporine A (CSA) or by depletion of CypD [448, 455, 456].”
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Metalloenzyme-like Activity of Alzheimer's Disease β-Amyloid
Opazo, C., Huang, X., Cherny, R. A., Moir, R. D., Roher, A. E., White, A. R., Cappai, R., Masters, C. L., Tanzi, R. E., Inestrosa, N. C., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206428200 · Cited by 580 · see citing works
The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production
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“Hypoxic conditions are considered to raise cytosolic ROS levels and, in this way, induce the activation of HIF (reviewed in [211]) probably in a mitochondrial complex III-dependent manner [212].”
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Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress.
Yan, S. D., Chen, X., Schmidt, A. M., Brett, J., Godman, G., Zou, Y. S., Scott, C. W., Caputo, C., Frappier, T., & Smith, M. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.16.7787 · Cited by 565 · cited 2× · see citing works
“Uptake of AGE-glycated tau into SH-SY5Y neuroblastoma cells was associated with malondialdehyde and HO-1 detection which was prevented by the exposure of these cells to N-acetylcysteine and probucol, two antioxidant compounds [116].”
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Increased expression of the amyloid precursor β‐secretase in Alzheimer's disease
Holsinger, R. M. D., McLean, C. A., Beyreuther, K., Masters, C. L., & Evin, G. (2002) · Annals of Neurology · doi:10.1002/ana.10208 · Cited by 562 · see citing works
Metal Binding and Oxidation of Amyloid-β within Isolated Senile Plaque Cores: Raman Microscopic Evidence
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“Increased levels of oxidative stress in the brain are reflected by increased brain content of copper (Cu) and zinc (Zn), specifically in the neuropil and in AD plaques [47, 48].”
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Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17
Chen, C.-D., Podvin, S., Gillespie, E., Leeman, S. E., & Abraham, C. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709805104 · Cited by 553 · cited 1× · see citing works
“The latter is released into the extracellular space upon insulin-mediated release by ADAM family members ADAM10 and ADAM17 [345].”
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Amyloid β-Peptide Impairs Glucose Transport in Hippocampal and Cortical Neurons: Involvement of Membrane Lipid Peroxidation
Mark, R. J., Pang, Z., Geddes, J. W., Uchida, K., & Mattson, M. P. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-03-01046.1997 · Cited by 551 · 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
Stimulation by calcium ions of pyruvate dehydrogenase phosphate phosphatase
Denton, R. M., Randle, P. J., & Martin, B. R. (1972) · Biochemical Journal · doi:10.1042/bj1280161 · Cited by 542 · see citing works
Hydrofluoric acid-treated tau PHF proteins display the same biochemical properties as normal tau.
Greenberg, S. G., Davies, P., Schein, J., & Binder, L. I. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48531-6 · Cited by 542 · cited 1× · see citing works
“Crosslinking of tau into paired helical filaments was shown to be driven by abnormal levels of phosphorylation, or hyperphosphorylation, of tau, which renders the protein insoluble and dysfunctional [377, 378].”
Background
Nuclear Factor E2-Related Factor 2-Dependent Antioxidant Response Element Activation by tert -Butylhydroquinone and Sulforaphane Occurring Preferentially in Astrocytes Conditions Neurons against Oxidative Insult
Kraft, A. D., Johnson, D. A., & Johnson, J. A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3817-03.2004 · Cited by 541 · cited 1× · see citing works
“The neuron-glial unit, the main interaction site between neurons and cells of glial origin such as astrocytes, regulates oxidative stress levels through an intimately linked intercellular mechanism for maintaining redox homeostasis [147, 148].”
Background
Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer’s disease: possible relation to oxidative stress.
Deibel, M. A., Ehmann, W. D., & Markesbery, W. R. (1996) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(96)00203-1 · Cited by 540 · see citing works
Cancer Chemoprevention Mechanisms Mediated Through the Keap1–Nrf2 Pathway
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In Situ Oxidative Catalysis by Neurofibrillary Tangles and Senile Plaques in Alzheimer’s Disease
Sayre, L. M., Perry, G. L., Harris, P. L. R., Liu, Y. A., Schubert, K. A., & Smith, M. A. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0740270.x · Cited by 538 · see citing works
Proteomic identification of nitrated proteins in Alzheimer's disease brain
Castegna, A., Thongboonkerd, V., Klein, J. B., Lynn, B. C., Markesbery, W. R., & Butterfield, D. A. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01786.x · Cited by 535 · see citing works
Neurotoxicity of Alzheimer’s disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio
Kuperstein, I., Broersen, K., Benilova, I., Rozenski, J., Jonckheere, W., Debulpaep, M., Vandersteen, A., Segers‐Nolten, I., Van Der Werf, K., Subramaniam, V., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.211 · Cited by 532 · see citing works
Self-citation
Cortical Cytochrome Oxidase Activity Is Reduced in Alzheimer's Disease
Mutisya, E. M., Bowling, A. C., & Beal, M. F. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.63062179.x · Cited by 531 · see citing works
Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration
Musiek, E. S., Lim, M. M., Yang, G., Bauer, A. Q., Qi, L., Lee, Y., Roh, J. H., Ortiz-Gonzalez, X., Dearborn, J. T., Culver, J. P., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70317 · Cited by 524 · see citing works
Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease
Srikanth, V., Maczurek, A., Phan, T., Steele, M., Westcott, B., Juskiw, D., & Münch, G. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.04.016 · Cited by 524 · cited 1× · see citing works
“The roles of RAGE and AGEs in AD pathogenesis have been covered in a number of reviews [426, 427].”
Background
Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl- l -carnitine and/or R -α-lipoic acid
Liu, J., Head, E., Gharib, A., Yuan, W., Ingersoll, R. T., Hagen, T. M., Cotman, C. W., & Ames, B. N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261709299 · Cited by 504 · cited 1× · see citing works
“increased in the hippocampus, cortical neurons, white matter and in the frontoparietal cortex of aged rats [37].”
Background
Electron transport chain defects in Alzheimer's disease brain
Parker, W. D., Parks, J. K., Filley, C. M., & Kleinschmidt-DeMasters, B. K. (1994) · Neurology · doi:10.1212/wnl.44.6.1090 · Cited by 495 · see citing works
Cyclophilin‐D binds strongly to complexes of the voltage‐dependent anion channel and the adenine nucleotide translocase to form the permeability transition pore
Crompton, M., Virji, S., & Ward, J. M. (1998) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1998.2580729.x · Cited by 492 · see citing works
Immunochemical detection of advanced glycosylation end products in vivo.
Makita, Z., Vlassara, H., Cerami, A., & Bucala, R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42741-x · Cited by 491 · cited 1× · see citing works
“AGEs are the product of non-enzymatic aldose-mediated glycated or oxidized proteins [422], and accumulation of AGEs was shown to be agingrelated [423, 424] and accelerates in conditions such as diabetes [425].”
Background
β‐Amyloid inhibits integrated mitochondrial respiration and key enzyme activities
Casley, C. S., Canevari, L., Land, J. M., Clark, J. B., & Sharpe, M. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2001.00681.x · Cited by 485 · cited 1× · see citing works
“using oxygen sensitive electrodes [419].”
Association of human aging with a functional variant of klotho
Arking, D. E., Krebsová, A., Maçek, M., Maçek, M., Arking, A., Mian, S. I., Fried, L. F., Hamosh, A., Dey, S., McIntosh, I., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.022484299 · Cited by 481 · see citing works
Amyloid β Protein Enhances the Survival of Hippocampal Neurons in Vitro
Whitson, J. S., Selkoe, D. J., & Cotman, C. W. (1989) · Science · doi:10.1126/science.2928783 · Cited by 469 · cited 1× · see citing works
“Supportive of such a hypothesis is the observation that A was found to act as a neurotrophic agent selectively at low nM concentrations while at higher peptide concentrations neurotrophic functionality was abolished [363, 373, 374].”
Background
Relative Abundance of Alzheimer A Beta Amyloid Peptide Variants in Alzheimer Disease and normal Aging
Näslund, J., Schierhorn, A., Hellman, U., Lannfelt, L., Roses, A. D., Tjernberg, L. O., Silberring, J., Gandy, S. E., Winblad, B., & Greengard, P. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8378 · Cited by 468 · cited 2× · see citing works
“APP23 transgenic mice show methionine oxidized forms of A 1-40 [64] and methionine oxidized A is also abundantly detected in AD patient brains [38, 63, 64].”
Background
Withdrawal of Survival Factors Results in Activation of the JNK Pathway in Neuronal Cells Leading to Fas Ligand Induction and Cell Death
Le-Niculescu, H., Bonfoco, E., Kasuya, Y., Claret, F.-X., Green, D. R., & Karin, M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.751 · Cited by 460 · cited 1× · see citing works
“More1249 over, members of the SAPK family were also found to 1250 be upregulated in AD patient brains [30, 313] and are 1251 activated by various stress signals including oxida1252 tive stress [314, 315].”
Background
Neuronal and glial calcium signaling in Alzheimer’s disease
Mattson, M. P., & Chan, S. L. (2003) · Cell Calcium · doi:10.1016/s0143-4160(03)00128-3 · Cited by 454 · see citing works
The effect of hyperoxia on superoxide production by lung submitochondrial particles
Turrens, J. F., Freeman, B. Α., Levitt, J. G., & Crapo, J. D. (1982) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(82)90518-5 · Cited by 448 · cited 1× · see citing works
“to ROS generation in rat and porcine lung [436],”
Background
SIRT3 Protein Deacetylates Isocitrate Dehydrogenase 2 (IDH2) and Regulates Mitochondrial Redox Status
Yu, W., Dittenhafer‐Reed, K. E., & Denu, J. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.355206 · Cited by 445 · cited 16× · see citing works
“A study involving 74 human subjects demonstrated that GSH levels of autopsied brains did not significantly decrease with aging [128].”
BackgroundInfluential
Impairment of Glucose and Glutamate Transport and Induction of Mitochondrial Oxidative Stress and Dysfunction in Synaptosomes by Amyloid β‐Peptide: Role of the Lipid Peroxidation Product 4‐Hydroxynonenal
Keller, J. N., Pang, Z., Geddes, J. W., Begley, J. G., Germeyer, A., Waeg, G., & Mattson, M. P. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69010273.x · Cited by 439 · see citing works
Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers.
Zlokovic, B. V., Martel, C. L., Matsubara, E., McComb, J. G., Zheng, G., McCluskey, R. T., Frangione, B., & Ghiso, J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.4229 · Cited by 430 · cited 1× · see citing works
“Multi-ligand receptor megalin has been identified to also act as receptor of clusterin [222].”
Background
Different Responses of Astrocytes and Neurons to Nitric Oxide: The Role of Glycolytically Generated ATP in Astrocyte Protection
Almeida, A., Almeida, J., Bolaños, J. P., & Moncada, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261560998 · Cited by 423 · see citing works
Induction of hypoxia‐inducible factor‐1 (HIF‐1) and its target genes following focal ischaemia in rat brain
Bergeron, M., Yu, A. Y., Solway, K., Semenza, G. L., & Sharp, F. R. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00845.x · Cited by 413 · see citing works
Presenilin clinical mutations can affect γ‐secretase activity by different mechanisms
Bentahir, M., Nyabi, O., Verhamme, J., Tolia, A., Horré, K., Wiltfang, J., Esselmann, H., & Strooper, B. D. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03578.x · Cited by 412 · cited 1× · see citing works
“ated processing of A PP in various ways [288].”
Background
Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid β-peptide
Yan, S. D., Yan, S. F., Chen, X., Fu, J., Chen, M., Kuppusamy, P., Smith, M. A., Perry, G., Godman, G. C., Nawroth, P., et al. (1995) · Nature Medicine · doi:10.1038/nm0795-693 · Cited by 406 · cited 2× · see citing works
“Instead of the uniformly elongated mitochondrial morphology observed in wild type mice, human AD brain and hippocampal mitochondria in mice carrying mutations for presenilin-1 (psen1), A PP, and tau, have an ovoid or teardrop profile [115].”
Background
Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease
Thambisetty, M., Simmons, A., Velayudhan, L., Hye, A., Campbell, J., Zhang, Y., Wahlund, L.-O., Westman, E., Kinsey, A., Güntert, A., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.78 · Cited by 405 · cited 1× · see citing works
“identified as a genetic determinant of AD [217] and plasma CLU levels were associated with atrophy of the entorhinal cortex and clinical progression of the disease [218] as well as with longitudinal brain atrophy in MCI patients [219].”
Background
The Structural Basis of Monoclonal Antibody Alz50's Selectivity for Alzheimer's Disease Pathology
Carmel, G., Mager, E. M., Binder, L. I., & Kuret, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.51.32789 · Cited by 402 · cited 1× · see citing works
“a conformational change in tau [104], coincides with”
Background
Protein‐Bound Acrolein
Calingasan, N. Y., Uchida, K., & Gibson, G. E. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0720751.x · Cited by 400 · see citing works
Increased Iron and Free Radical Generation in Preclinical Alzheimer Disease and Mild Cognitive Impairment
Smith, M. A., Zhu, X., Tabaton, M., Liu, G., McKeel, D. W., Cohen, M. L., Wang, X., Siedlak, S. L., Dwyer, B. E., Hayashi, T., et al. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1239 · Cited by 400 · cited 1× · see citing works
“Also in preclinical stages and MCI Fe2+ levels were increased in the cortex and cerebellum and correlated with generation of radicals [173].”
Background
Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase
MacAllister, R. J., Parry, H., Kimoto, M., Ogawa, T., Russell, R. J., Hodson, H. F., Whitley, G. S. J., & Vallance, P. J. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb16069.x · Cited by 394 · cited 1× · see citing works
“This enzyme regulates the activity of nitric oxide synthase [101].”
Background
Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer's disease
Williams, T. I., Lynn, B. C., Markesbery, W. R., & Lovell, M. A. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.06.004 · Cited by 391 · cited 1× · see citing works
“and in vivo as a result of lipid peroxidation [76, 77].”
Background
Oxidative stress increases expression and activity of BACE in NT2 neurons
Tamagno, E., Bardini, P., Obbili, A., Vitali, A., Borghi, R., Zaccheo, D., Pronzato, M. A., Danni, O., Smith, M. A., Perry, G., et al. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0515 · Cited by 385 · see citing works
Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments.
Schweers, O., Mandelkow, E., Biernat, J., & Mandelkow, E. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.18.8463 · Cited by 379 · cited 1× · see citing works
“isoform of tau into such assemblies [107].”
An intracellular protein that binds amyloid-β peptide and mediates neurotoxicity in Alzheimer's disease
Du Yan, S., Fu, J., Soto, C., Chen, X., Zhu, H., Al-Mohanna, F., Collison, K., Zhu, A., Stern, E., Saido, T., et al. (1997) · Nature · doi:10.1038/39522 · Cited by 379 · see citing works
Activation of p38 Kinase Links Tau Phosphorylation, Oxidative Stress, and Cell Cycle-Related Events in Alzheimer Disease
Zhu, X., Rottkamp, C. A., Boux, H., Takeda, A., Perry, G., & Smith, M. A. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.10.880 · Cited by 378 · cited 2× · see citing works
“be upregulated in AD patient brains [30, 313] and are”
Background
Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: Insights into the development of Alzheimer's disease
Butterfield, D. A., Poon, H. F., St. Clair, D., Keller, J. N., Pierce, W. M., Klein, J. B., & Markesbery, W. R. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.11.002 · Cited by 377 · see citing works
Inhibition of energy metabolism alters the processing of amyloid precursor protein and induces a potentially amyloidogenic derivative
Gabuzda, D., Busciglio, J., Chen, L. B., Matsudaira, P., & Yankner, B. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36875-8 · Cited by 373 · cited 1× · see citing works
“Details of A PP 1137 processing have been extensively covered in a number 1138 of reviews [81, 285].”
Background
Copper Mediates Dityrosine Cross-Linking of Alzheimer's Amyloid-β
Atwood, C., Perry, G. L., Zeng, H., Kato, Y., Jones, W. D., Ling, K.-Q., Huang, X., Moir, R. D., Wang, D., Sayre, L. M., et al. (2003) · Biochemistry · doi:10.1021/bi0358824 · Cited by 371 · see citing works
ApoE4 reduces glutamate receptor function and synaptic plasticity by selectively impairing ApoE receptor recycling
Chen, Y., Durakoglugil, M. S., Xian, X., & Herz, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914984107 · Cited by 368 · cited 1× · see citing works
“The pathogenic origins of ApoE4 have been studied to great length and indicate that ApoE4 is involved in processes such as aggregation and clearance of A [240, 241], mitochondrial dysfunction, and impairment of calcium [242, 243] or cellular iron homeostasis [244], and ApoE4 affects synaptic architecture and functioni…”
Background
Changes in the Sleep and Waking EEGs of Nondemented and Demented Elderly Subjects
Prinz, P. N., Peskind, E. R., VITALIANO, P. P., Raskind, M. A., Eisdorfer, C., ZEMCUZNIKOV, H. N., & Gerber, C. J. (1982) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1982.tb01279.x · Cited by 367 · see citing works
Clusterin (apoJ) Alters the Aggregation of Amyloid β-Peptide (Aβ1-42) and Forms Slowly Sedimenting Aβ Complexes That Cause Oxidative Stress
Oda, T., Wals, P., Osterburg, H. H., Johnson, S. A., Pasinetti, G. M., Morgan, T. E., Rozovsky, I., Stine, W. B., Snyder, S. W., Holzman, T. F., et al. (1995) · Experimental Neurology · doi:10.1006/exnr.1995.1080 · Cited by 352 · cited 1× · see citing works
“Apart from an antioxidative effect of CLU, an indirect role of CLU actually promoting oxidative stress has been described showing that the presence of CLU induces the formation of slowly sedimenting complexes composed of SDS-resistant synthetic A assemblies that, in turn, induced oxidative stress in PC12 cells [235].”
Background
Calcium signaling and molecular mechanisms underlying neurodegenerative diseases
Pchitskaya, E. I., Александровна, П. Е., & Борисович, Б. И. (2017) · Cell Calcium · doi:10.1016/j.ceca.2017.06.008 · Cited by 346 · see citing works
Oxidative stress activates a positive feedback between the γ‐ and β‐secretase cleavages of the β‐amyloid precursor protein
Tamagno, E., Guglielmotto, M., Aragno, M., Borghi, R., Autelli, R., Giliberto, L., Muraca, G., Danni, O., Zhu, X., Smith, M. A., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05072.x · Cited by 338 · see citing works
Transferrin and Iron in Normal, Alzheimer's Disease, and Parkinson's Disease Brain Regions
Loeffler, D. A., Connor, J. R., Juneau, P. L., Snyder, B. S., Kanaley, L., DeMaggio, A. J., Nguyen, H., Brickman, C. M., & LeWitt, P. A. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65020710.x · Cited by 334 · cited 1× · see citing works
“homeostasis has been observed in various neurode699 generative disorders including AD [170].”
Background
Redox proteomics identification of oxidized proteins in Alzheimer's disease hippocampus and cerebellum: An approach to understand pathological and biochemical alterations in AD
Rukhsana Sultana, A., Debra Boyd-kimball, A., Poon, H. F., Cai, J., Pierce, W. M. J., Klein, J. B., Merchant, M. L., Markesbery, W. R., & Butterfield, D. A. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.021 · Cited by 334 · see citing works
RAGE potentiates Aβ‐induced perturbation of neuronal function in transgenic mice
Arancio, O., Zhang, H. P., Chen, X., Lin, C., Trinchese, F., Puzzo, D., Liu, S., Hegde, A. N., Yan, S. F., Stern, A., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600415 · Cited by 328 · cited 1× · see citing works
“The offspring of a transgenic RAGE overexpressing mouse model crossed with Tg APP animals showed neuronal perturbation already at 3-4 months of age, and astrogliosis and reactive microglia at 14–18 months [428].”
Background
Mitochondrial permeability transition pore is a potential drug target for neurodegeneration
Rao, V. K., Carlson, E. A., & Yan, S. S. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.003 · Cited by 325 · cited 1× · see citing works
“As a result of these observations, various studies embarked on targeting CypD/mPTP inhibition as potential treatment for neurodegenerative diseases [467, 468].”
Background
β‐Site APP cleaving enzyme up‐regulation induced by 4‐hydroxynonenal is mediated by stress‐activated protein kinases pathways
Tamagno, E., Parola, M., Bardini, P., Piccini, A., Borghi, R., Guglielmotto, M., Santoro, G., Davit, A., Danni, O., Smith, M. A., et al. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02895.x · Cited by 324 · cited 16× · see citing works
“In human SK-N-BE neuroblastoma cells, which were exposed to HNE- or H2O2mediated oxidative stress, an increase in A level was found that could be attributed indirectly to - secretase in a c-jun N-terminal kinase (JNK)/c-jun pathway/BACE1 dependent manner [75].”
BackgroundInfluential
Disrupted daily activity/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer's dementia
Hatfield, C. F. (2004) · Brain · doi:10.1093/brain/awh129 · Cited by 323 · see citing works
Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain.
Zhang, J., & Piantadosi, C. A. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115980 · Cited by 320 · cited 1× · see citing works
“Various conditions have been associated with 839 increased brain oxidative stress and neuronal apop840 tosis in response to hypoxia, including sleep apnea 841 [197, 198], exposure to carbon monoxide [199], and 842 ischemia [200].”
Background
Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity
Chang, S., Ma, T. R., Miranda, R. D., Balestra, M. E., Mahley, R. W., & Huang, Y. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508254102 · Cited by 319 · cited 1× · see citing works
“ance of A [240, 241], mitochondrial dysfunction, 972 and impairment of calcium [242, 243] or cellular 973 iron homeostasis [244], and ApoE4 affects synaptic 974 architecture and functioning [245, 246].”
Background
Oxidative Stress in Alzheimer’s Disease: Why Did Antioxidant Therapy Fail?
Persson, T., Popescu, B. O., & Cedazo-Mı́nguez, Á. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/427318 · Cited by 318 · see citing works
Cognition impairment in the genetic model of aging klotho gene mutant mice: a role of oxidative stress
Nagai, T., Yamada, K., Kim, H., Kim, Y., Noda, Y., Imura, A., Nabeshima, Y., & Nabeshima, T. (2002) · The FASEB Journal · doi:10.1096/fj.02-0448fje · Cited by 312 · cited 1× · see citing works
“Mutation of klotho in a transgenic mouse model demonstrated increased levels of 8-OHdG and malondialdehyde in the hippocampus in an age-dependent manner [356].”
Background
Mitochondria and Ca2+in cell physiology and pathophysiology
Duchen, M. R. (2000) · Cell Calcium · doi:10.1054/ceca.2000.0170 · Cited by 310 · see citing works
Intermittent Hypoxia Is Associated with Oxidative Stress and Spatial Learning Deficits in the Rat
Row, B. W., Liu, R., Xu, W., Kheirandish, L., & Gozal, D. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200209-1050oc · Cited by 307 · see citing works
Identification and purification of a human immunoglobulin-enhancer-binding protein (NF-kappa B) that activates transcription from a human immunodeficiency virus type 1 promoter in vitro.
Kawakami, K., Scheidereit, C., & Roeder, R. G. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.13.4700 · Cited by 306 · cited 5× · see citing works
“The redox state regulates activation and nuclear translocation of NFκB [180], and, as such, ROS was found to induce phosphorylation of IκB via activation of responsible kinases [181, 182].”
BackgroundInfluential
A Novel Function of Monomeric Amyloid β-Protein Serving as an Antioxidant Molecule against Metal-Induced Oxidative Damage
Zou, K., Gong, J.-S., Yanagisawa, K., & Michikawa, M. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-12-04833.2002 · Cited by 305 · cited 3× · see citing works
“Supportive of such a hypothesis is the observation that A was found to act as a neurotrophic agent selectively at low nM concentrations while at higher peptide concentrations neurotrophic functionality was abolished [363, 373, 374].”
Background
Oxidative Stress Induces Intracellular Accumulation of Amyloid β-Protein (Aβ) in Human Neuroblastoma Cells
Misonou, H., Morishima-Kawashima, M., & Ihara, Y. (2000) · Biochemistry · doi:10.1021/bi000169p · Cited by 304 · see citing works
Age-dependent accumulation of N.epsilon.-(carboxymethyl)lysine and N.epsilon.-(carboxymethyl)hydroxylysine in human skin collagen
Dunn, J. A., McCance, D. R., Thorpe, S. R., Lyons, T. J., & Baynes, J. (1991) · Biochemistry · doi:10.1021/bi00219a007 · Cited by 304 · cited 1× · see citing works
“related [423, 424] and accelerates in conditions such 1760 as diabetes [425].”
Background
Decreased Melatonin Levels in Postmortem Cerebrospinal Fluid in Relation to Aging, Alzheimer’s Disease, and Apolipoprotein E-ε4/4 Genotype1
Liu, R.-Y., Zhou, J.-N., van Heerikhuize, J., Hofman, M. A., & Swaab, D. F. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.1.5394 · Cited by 304 · cited 1× · see citing works
“Even though aging is related 629 to a decrease in CSF melatonin levels, presenile and 630 senile AD patients demonstrated an even stronger 631 reduction in melatonin levels that was shown to be 632 dependent on apolipoprotein genotype [146], one of 633 the strongest identified genetic correlates with AD.”
Background
The DBP gene is expressed according to a circadian rhythm in the suprachiasmatic nucleus and influences circadian behavior
Lopez‐Molina, L., Conquet, F., Dubois‐Dauphin, M., & Schibler, U. (1997) · The EMBO Journal · doi:10.1093/emboj/16.22.6762 · Cited by 300 · cited 1× · see citing works
“On the other hand, brain and peripheral tissues were shown to differ in their peroxiredoxin oxidation rhythms [324] as well as in other clock components [325].”
Background
Nerve endings from rat brain tissue release copper upon depolarization. A possible role in regulating neuronal excitability.
Kardos, J., Kovács, I., Hajós, F., Kálmán, M., & Simonyi, M. (1989) · Neuroscience Letters · doi:10.1016/0304-3940(89)90565-x · Cited by 298 · cited 1× · see citing works
“inhibiting the rat excitatory NMDA receptor [164], 689 and rat GABA receptor [164, 165].”
Background
[Apolipoprotein E polymorphism and Alzheimer disease].
van der Weide, J., Steijns, L. S. W., Jl, T., Wj, N., & Klaverwijden, G. (1996) · PubMed · Cited by 297 · see citing works
Intrahippocampal injection of a lentiviral vector expressing Nrf2 improves spatial learning in a mouse model of Alzheimer's disease
Kanninen, K. M., Heikkinen, R., Malm, T., Rõlova, T., Kemppainen, S., Leinonen, H. M., Ylä‐Herttuala, S., Tanila, H., Levonen, A., Koistinaho, M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908397106 · Cited by 293 · cited 5× · see citing works
“Spatial link between amyloid plaques and cells exhibiting oxidative damage A multiphoton microscopy-based study using the genetically encoded calcium indicator Yellow Cameleon 3.6 packaged into an adeno-associated virus (AAV2) and expressed in the brains of adult transgenic APP/PS1 mice showed that calcium overloaded…”
BackgroundInfluential
Activation of c-Jun N-Terminal Kinase and p38 in an Alzheimer's Disease Model Is Associated with Amyloid Deposition
Savage, M. J., Lin, Y.-G., Ciallella, J. R., Flood, D. G., & Scott, R. W. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03376.2002 · Cited by 291 · cited 1× · see citing works
“Pre1197 treatment of these NT2 cells with -tocopherol 1198 prevented BACE induction and CTF generation 1199 demonstrating direct involvement of oxidative stress 1200 in inducing BACE activity [81, 297].”
Background
Amyloid-β peptide binds with heme to form a peroxidase: Relationship to the cytopathologies of Alzheimer’s disease
Atamna, H., & Boyle, K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600134103 · Cited by 291 · see citing works
Oxidative stress and inflammation in iron‐overloaded patients with β‐thalassaemia or sickle cell disease
Walter, P. B., Fung, E. B., Killilea, D. W., Jiang, Q., Hudes, M. L., Madden, J., Porter, J. B., Evans, P., Vichinsky, E. P., & Harmatz, P. (2006) · British Journal of Haematology · doi:10.1111/j.1365-2141.2006.06277.x · Cited by 288 · cited 1× · see citing works
“myocardial infarction [18], sickle cell disease [19],”
Role of RAGE in Alzheimer’s Disease
Cai, Z., Liu, N., Wang, C., Qin, B., Zhou, Y., Xiao, M., Chang, L., Yan, L., & Zhao, B. (2015) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-015-0233-3 · Cited by 286 · cited 1× · see citing works
“The roles of RAGE and AGEs in AD pathogenesis have been covered in a number of reviews [426, 427].”
Background
SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression
Jacobs, K. M., Pennington, J. D., Bisht, K. S., Aykin‐Burns, N., Kim, H., Mishra, M. V., Sun, L., Nguyen, P., Ahn, B., Leclerc, J., et al. (2008) · International Journal of Biological Sciences · doi:10.7150/ijbs.4.291 · Cited by 281 · cited 1× · see citing works
“NAD+-dependent deacetylase SirT3 is an important regulator of energy production and redox response by reduction of GSH [331, 332], mediating the upregulation of SOD2 and catalase [333], and activation of SOD2 [334].”
Background
Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer’s disease
Atamna, H., & Frey, W. H. (2007) · Mitochondrion · doi:10.1016/j.mito.2007.06.001 · Cited by 278 · cited 1× · see citing works
“is significantly decreased in the AD brain [87].”
Background
Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice
Li, F., Calingasan, N. Y., Yu, F., Mauck, W. M., Toidze, M., Almeida, C. G., Takahashi, R. H., Carlson, G. A., Beal, M. F., Lin, M. T. S., et al. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02455.x · Cited by 276 · see citing works
Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment
Markesbery, W. R., Kryscio, R. J., Lovell, M. A., & Morrow, J. D. (2005) · Annals of Neurology · doi:10.1002/ana.20629 · Cited by 272 · cited 1× · see citing works
“809 Consistent with this, an earlier longitudinal study on 810 autopsied control and patient brains demonstrated 811 that levels of isoprostane (F2) and F4-neuroprostane 812 were increased in both amnestic MCI and late stage 813 AD patients in various regions of the brain [189].”
Result
Antioxidant clinical trials in mild cognitive impairment and Alzheimer's disease
Mecocci, P., & Polidori, M. C. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.006 · Cited by 270 · see citing works
Aβ and Tau Toxicities in Alzheimer's Are Linked via Oxidative Stress-Induced P38 Activation: Protective Role of Vitamin E
Giraldo, E., Lloret, A., Fuchsberger, T., & Viña, J. (2014) · Redox Biology · doi:10.1016/j.redox.2014.03.002 · Cited by 268 · see citing works

Flagged first, then by citations

4 of the 475 references couldn’t be matched to a known paper.

Sorted by citations

The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies
Juan, C. A., Pérez de la Lastra, J. M., Plou, F. J., & Pérez-Lebeña, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094642 · Cited by 2,810 · see citing works
“In Huntington’s disease, the mutant huntingtin protein causes mitochondrial dysfunction, with higher levels of ROS and increased oxidative stress [33].”
Background
Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130 · see citing works
“Oxidative damage has been implicated in all major neurodegenerative diseases including Alzheimer’s disease (AD) [108,109], Parkinson’s disease (PD) [110,111], Huntington’s disease (HD) [112,113], amyotrophic lateral sclerosis (ALS) [114], and multiple sclerosis (MS) [115].”
Background
An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases
Teleanu, D. M., Niculescu, A.-G., Lungu, I. I., Radu, C. I., Vladâcenco, O., Roza, E., Costăchescu, B., Grumezescu, A. M., & Teleanu, R. I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23115938 · Cited by 1,085 · see citing works
“HNE can be detected at the early stages of AD progress, while its levels have been reported to be proportional to the extent of neuronal lesions [47].”
Background
The Link between Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation in the Pathophysiology of Alzheimer’s Disease: Therapeutic Implications and Future Perspectives
Jurcău, M. C., Andronie-Cioara, F. L., Jurcău, A., Marcu, F., Ţiț, D. M., Pașcalău, N., & Nistor-Cseppentö, D. C. (2022) · Antioxidants · doi:10.3390/antiox11112167 · Cited by 226 · see citing works
“With aging, cerebral glucose metabolism progressively declines as a result of changes in brain insulin and cortisol levels [46] and of decreased activity of synaptic ATPases [47], leading to a 45% reduced cerebral glucose utilization [46].”
Background
The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging
Yang, L., Chen, Y., Liu, Y., Xing, Y., Miao, C., Zhao, Y., Chang, X., & Zhang, Q. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.617843 · Cited by 231 · see citing works
Role of reactive oxygen species in the progression of Alzheimer’s disease
Bhatt, S., Puli, L., & Patil, C. R. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.12.004 · Cited by 207 · see citing works
Oxidative Stress Occurs Prior to Amyloid Aβ Plaque Formation and Tau Phosphorylation in Alzheimer’s Disease: Role of Glutathione and Metal Ions
Roy, R. G., Mandal, P. K., & Maroon, J. C. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00486 · Cited by 194 · see citing works
Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses
(2024) · aging and disease · doi:10.14336/ad.2023.0608 · Cited by 183 · see citing works
“Oxidative stress in the cortex and hippocampal tissues is a common characteristic of AD [145].”
Background
Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer’s Disease Progression
Andronie-Cioară, F. L., Ardelean, A. I., Nistor-Cseppento, C. D., Jurcău, A., Jurcău, M. C., Pașcalău, N., & Marcu, F. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031869 · Cited by 164 · see citing works
When It Comes to an End: Oxidative Stress Crosstalk with Protein Aggregation and Neuroinflammation Induce Neurodegeneration
Michalska, P., & Leon, R. M. (2020) · Antioxidants · doi:10.3390/antiox9080740 · Cited by 112 · see citing works
Potential Roles of Redox Dysregulation in the Development of Schizophrenia
Perkins, D. O., Jeffries, C. D., & Do, K. Q. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.03.016 · Cited by 103 · see citing works
Axonal Degeneration in AD: The Contribution of Aβ and Tau
Salvadores, N., Gerónimo‐Olvera, C., & Court, F. A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.581767 · Cited by 97 · see citing works
“In the context of AD, different pathogenic pathways have been shown to contribute to axon demise, including calcium signaling imbalance, mitochondrial dysfunction, alterations in axonal transport, and increased oxidative stress (Bamburg and Bloom, 2009; Yu et al., 2009; Ye et al., 2012; Cioffi et al., 2019; Guo et al.…”
Background
Harnessing endophenotypes and network medicine for Alzheimer's drug repurposing
Fang, J., Pieper, A. A., Nussinov, R., Lee, G., Bekris, L. M., Leverenz, J. B., Cummings, J. L., & Cheng, F. (2020) · Medicinal Research Reviews · doi:10.1002/med.21709 · Cited by 93 · see citing works
“The detailed molecular mechanisms and genetics of oxidative stress in AD were comprehensive described in a previous Review.55 Proteostasis refers to the dysfunction in protein homeostasis, leading to the accumulation of protein aggregates.56 Targeting endoplasmic reticulum acetylation to improve proteostasis in the se…”
Background
Association between short-term exposure to ambient particulate air pollution and biomarkers of oxidative stress: A meta-analysis
Li, Z., Liu, Q., Xu, Z., Guo, X., & Wu, S. (2020) · Environmental Research · doi:10.1016/j.envres.2020.110105 · Cited by 92 · see citing works
Cognitive disorder and dementia in type 2 diabetes mellitus
Ortíz, G. G., Huerta, M., González-Usigli, H., Torres-Sánchez, E. D., Delgado-Lara, D. L. C., Pacheco-Moisés, F. P., Mireles-Ramírez, M. A., Torres-Mendoza, B. M., Moreno-Cih, R. I., & Velázquez-Brizuela, I. E. (2022) · World Journal of Diabetes · doi:10.4239/wjd.v13.i4.319 · Cited by 90 · see citing works
Oxygen metabolism abnormality and Alzheimer's disease: An update
Liu, G., Yang, C., Wang, X., Chen, X., Wang, Y., & Le, W. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102955 · Cited by 85 · see citing works
“Chronic hypoxia can upregulate NOX in AD, potentially leading to an increase in O 2 - [ • Excessive ROS can impair mitochondrial function, which can further promote ROS generation, thereby promoting the progression of AD [85].”
Background
Redox changes and cellular senescence in Alzheimer's disease
Yu, N., Pasha, M., & Chua, J. J. E. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103048 · Cited by 80 · see citing works
Recent developments in the probiotics as live biotherapeutic products (LBPs) as modulators of gut brain axis related neurological conditions
Ağagündüz, D., Bingöl, F. G., Çelik, E., Cemali, Ö., Özenir, Ç., Özoğul, F., & Capasso, R. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03609-y · Cited by 79 · see citing works
“In addition, an increase in reactive oxygen strain is associated with an increase in the oxidation of DNA, proteins, and lipids [93, 94].”
Background
Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies
Meng, K., Jia, H., Hou, X., Zhu, Z., Lu, Y., Feng, Y., Feng, J., Xia, Y., Tan, R., Cui, F., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13020327 · Cited by 80 · see citing works
“Similarly, the antioxidant capacity of ALS mice is impaired, and the level of ROS in the spinal cord is significantly increased, leading to DNA damage, lipid oxidation, protein oxidation and aggregation, inflammatory response, and apoptosis [110,111].”
The Role of the Transcription Factor Nrf2 in Alzheimer’s Disease: Therapeutic Opportunities
Plano, L. M. D., Calabrese, G., Rizzo, M. G., Oddo, S., & Caccamo, A. (2023) · Biomolecules · doi:10.3390/biom13030549 · Cited by 78 · see citing works
“Under physiological conditions, an increase in ROS stimulates cells to produce a series of antioxidant molecules to prevent oxidative damage [10].”
Background
Brain metabolism in Alzheimer’s disease: biological mechanisms of exercise
Xu, L., Liu, R., Qin, Y., & Wang, T. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00364-y · Cited by 78 · see citing works
“Excessive oxidative stress [153], metabolic disturbances [154] and neuroinflammation [155] in the brain mediate the accumulation of abnormal proteins in the context of AD.”
Background
Potential use of antioxidants for the treatment of chronic inflammatory diseases
Blagov, A. V., Summerhill, V. I., Sukhorukov, V. N., Zhigmitova, E. B., Postnov, A. Y., & Orekhov, A. N. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1378335 · Cited by 72 · see citing works
A review on omics-based biomarkers discovery for Alzheimer's disease from the bioinformatics perspectives: Statistical approach vs machine learning approach
Tan, M. S., Cheah, P., Chin, A., Looi, L., & Chang, S. (2021) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2021.104947 · Cited by 64 · see citing works
The relationship between adult hippocampal neurogenesis and cognitive impairment in Alzheimer's disease
Geigenmüller, J. N., Tari, A. R., Wisløff, U., & Walker, T. L. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14179 · Cited by 64 · see citing works
“114 In a study using post mortem tissue of AD patients, Cruz-Sánchez et al. showed that the AD hippocampus is characterized by elevated markers of oxidative stress.”
Salivary gland dysfunction and salivary redox imbalance in patients with Alzheimer’s disease
Zalewska, A., Klimiuk, A., Zięba, S., Wnorowska, O., Rusak, M., Waszkiewicz, N., Szarmach, I. J., Dzierżanowski, K., & Maciejczyk, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-03456-9 · Cited by 56 · see citing works
Effects and mechanisms of natural products on Alzheimer’s disease
Yang, Z., Zhou, D.-D., Huang, S., Fang, A., Li, H., & Zhu, H. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1985428 · Cited by 59 · see citing works
“Oxidative stress interconnects with Aβ deposition, tau hyperphosphorylation, and loss of synapses and neurons (Cioffi, Adam, and Broersen 2019; Zhao and Zhao 2013).”
Background
Fruit Quality Characterization of New Sweet Cherry Cultivars as a Good Source of Bioactive Phenolic Compounds with Antioxidant and Neuroprotective Potential
Antognoni, F., Potente, G., Mandrioli, R., Angeloni, C., Freschi, M., Malaguti, M., Hrelia, S., Lugli, S., Gennari, F., Muzzi, E., et al. (2020) · Antioxidants · doi:10.3390/antiox9080677 · Cited by 55 · see citing works
“Strong evidence suggests that oxidative stress plays a key role in important neurodegenerative syndromes, such as Parkinson’s [22] and Alzheimer’s diseases [23].”
Background
Redox Homeostasis and Prospects for Therapeutic Targeting in Neurodegenerative Disorders
Akanji, M. A., Rotimi, D. E., Elebiyo, T. C., Awakan, O. J., & Adeyemı, O. S. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/9971885 · Cited by 52 · see citing works
“of guanosine bases to 8-hydroxyguanosine, in brain regions that coordinate cognitive and emotional functions has also been documented [95].”
Background
In silico screening of glycogen synthase kinase-3β targeted ligands against acetylcholinesterase and its probable relevance to Alzheimer’s disease
Jabir, N. R., Shakil, S., Tabrez, S. S. M., Khan, M. S., Rehman, M. T., & Ahmed, A. B. A. (2020) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2020.1784796 · Cited by 52 · see citing works
“The formation and accumulation of amyloid fibers, intracellular neurofibrillary tangles, inflammation, oxidative stress, iron dysregulation and ultimate destruction of the functional activities of neurons are some of the mechanisms of AD (Aliev et al., 2014; Cioffi et al., 2019).”
Background
Trilobatin Protects Against Aβ25–35-Induced Hippocampal HT22 Cells Apoptosis Through Mediating ROS/p38/Caspase 3-Dependent Pathway
Chen, N., Wang, J., He, Y., Xu, Y., Zhang, Y., Gong, Q., Yu, C., & Gao, J. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00584 · Cited by 49 · see citing works
Graphene Oxide Ameliorates the Cognitive Impairment Through Inhibiting PI3K/Akt/mTOR Pathway to Induce Autophagy in AD Mouse Model
Chu, F., Li, K., Li, X., Xu, L., Huang, J., & Yang, Z. R. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03167-z · Cited by 49 · see citing works
Oxidative Stress: Pathological Driver in Chronic Neurodegenerative Diseases
Chong, Z. Z., & Souayah, N. (2025) · Antioxidants · doi:10.3390/antiox14060696 · Cited by 50 · see citing works
PI3K/Akt and ERK1/2 Signalling Are Involved in Quercetin-Mediated Neuroprotection against Copper-Induced Injury
Zubčić, K., Radovanović, V., Vlainić, J., Hof, P. R., Oršolić, N., Šimić, G., & Jembrek, M. J. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/9834742 · Cited by 46 · see citing works
“Cu binding to Aβ increases its ability to form ubiquitin-containing aggregates and greatly promotes Aβ-induced generation of ROS [10, 14, 15].”
Background
Neuroprotective Activity of Melittin—The Main Component of Bee Venom—Against Oxidative Stress Induced by Aβ25–35 in In Vitro and In Vivo Models
Nguyen, C. D., & Lee, G. (2021) · Antioxidants · doi:10.3390/antiox10111654 · Cited by 46 · see citing works
“This is considered a major cause of the onset of cognitive dysfunction [12,13,39].”
Background
Phytochemical and Toxicological Effect of Ethanol Extract of Heliotropium Indicum on Liver of Male Albino Rats
(2020) · Letters in Applied NanoBioScience · doi:10.33263/lianbs102.20852095 · Cited by 41 · see citing works
“Oxidative stress has likewise been implicated in several disease conditions, including malignant growth [24], neurodegenerative sicknesses such as Alzheimer’s [25], Parkinson's [26], Huntington [27], amyotrophic lateral sclerosis [28], diabetes [29], ulcer [30], among others.”
Background
Multiple chemical sensitivity: It's time to catch up to the science
Molot, J., Sears, M., & Anisman, H. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105227 · Cited by 40 · see citing works
Brain organoids: A promising model to assess oxidative stress‐induced central nervous system damage
Oyefeso, F. A., Muotri, A. R., Wilson, C. G., & Pecaut, M. J. (2021) · Developmental Neurobiology · doi:10.1002/dneu.22828 · Cited by 44 · see citing works
“Protein aggregates are known risk factors repeatedly identified in patients with neurodegenerative diseases, although the mechanisms by which they contribute to these diseases are not fully understood (Cioffi et al., 2019; Olivares et al., 2009).”
Background
Implication of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase and Its Inhibitors in Alzheimer’s Disease Murine Models
Morales, L. G. F., Correa‐Basurto, J., & Rosales‐Hernández, M. C. (2021) · Antioxidants · doi:10.3390/antiox10020218 · Cited by 38 · see citing works
“Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory loss due to multiple factors, including the generation of reactive oxygen species (ROS) [1,2].”
Background
Nutraceuticals-based therapeutic approach: recent advances to combat pathogenesis of Alzheimer’s disease
Talebi, M., Kakouri, E., Talebi, M., Tarantilis, P. Α., Farkhondeh, T., İlgün, S., Pourbagher‐Shahri, A. M., & Samarghandian, S. (2021) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2021.1923479 · Cited by 39 · see citing works
“Oxidative stress seems to play a crucial role in the pathogenesis of AD [22,23].”
Background
Traditional Chinese medicine for the treatment of Alzheimer's disease: A focus on the microbiota–gut–brain axis
Ma, L., Jiang, X., Huang, Q.-Y., Chen, W., Zhang, H., Pei, H., Cao, Y., Wang, H., & Li, H. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115244 · Cited by 38 · see citing works
Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs
Moos, W. H., Faller, D. V., Glavas, I. P., Harpp, D. N., Kanara, I., Mavrakis, A. N., Pernokas, J., Pernokas, M., Pinkert, C. A., Powers, W. R., et al. (2020) · BioResearch open access · doi:10.1089/biores.2020.0004 · Cited by 36 · see citing works
FOXO and related transcription factors binding elements in the regulation of neurodegenerative disorders
Oli, V., Gupta, R. V., & Kumar, P. (2021) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2021.102012 · Cited by 36 · see citing works
Reducing particulates in indoor air can improve the circulation and cardiorespiratory health of old people: A randomized, double-blind crossover trial of air filtration
Guo, M., Du, C., Li, B., Yao, R., Tang, Y., Jiang, Y., Liu, H., Su, H., Zhou, Y., Wang, L., et al. (2021) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2021.149248 · Cited by 35 · see citing works
“An increasing number of studies have shown that increased oxidative stress is a potential biological pathway behind the adverse health effects of ambient PM on cardiovascular health, respiratory health and nervous system health (Cioffi et al. 2019; Hecker 2018; Rao et al. 2018).”
Background
Pomegranate (Punica granatum L.) Extract Effects on Inflammaging
Cordiano, R., Gammeri, L., Salvo, E. D., Gangemi, S., & Minciullo, P. L. (2024) · Molecules · doi:10.3390/molecules29174174 · Cited by 38 · see citing works
Subchronic neurotoxicity of diazinon in albino mice: Impact of oxidative stress, AChE activity, and gene expression disturbances in the cerebral cortex and hippocampus on mood, spatial learning, and memory function
Karimani, A., Ramezani, N., Goli, A. A., Shirazi, M. H. N., Nourani, H., & Jafari, A. M. (2021) · Toxicology Reports · doi:10.1016/j.toxrep.2021.06.017 · Cited by 33 · see citing works
The NLRP3 inflammasome as a bridge between neuro-inflammation in metabolic and neurodegenerative diseases
Söderbom, G., & Zeng, B. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.03.023 · Cited by 31 · see citing works
Upregulation of Cortical A 2A Adenosine Receptors Is Reflected in Platelets of Patients with Alzheimer’s Disease
Merighi, S., Battistello, E., Casetta, I., Gragnaniello, D., Poloni, T. E., Medici, V., Cirrincione, A., Varani, K., Vincenzi, F., Borea, P. A., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201437 · Cited by 32 · see citing works
“Notably, the abnormal accumulation of A (cid:2) is responsible for important detrimental effects, including oxidative stress injury, which then results in neuronal death [56].”
α7nAChR activation protects against oxidative stress, neuroinflammation and central insulin resistance in ICV-STZ induced sporadic Alzheimer's disease
Yamini, P., Ray, R. S., Yadav, S., Dhaliwal, J., Yadav, M., Kondepudi, K. K., & Chopra, K. (2022) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2022.173402 · Cited by 31 · see citing works
The function of sphingolipids in different pathogenesis of Alzheimer's disease: A comprehensive review
Wang, X., Li, H., Sheng, Y., He, B., Liu, Z., Li, W., Yu, S., Wang, J., Zhang, Y., Chen, J., et al. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.116071 · Cited by 29 · see citing works
Anticancer Activity of Astaxanthin-Incorporated Chitosan Nanoparticles
Hwang, E. J., Jeong, Y., Lee, K.-J., Yu, Y.-B., Ohk, S., & Lee, S. (2024) · Molecules · doi:10.3390/molecules29020529 · Cited by 28 · see citing works
“For example, oxidative stress has a deep relationship with the progress of Alzheimer’s disease and then aggravates its symptoms [37–39].”
Background
Revolutionizing neurotherapeutics: Nanocarriers unveiling the potential of phytochemicals in Alzheimer's disease
Kamath, A. P., Nayak, P. G., John, J., Mutalik, S., Balaraman, A. K., & Nandakumar, K. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110096 · Cited by 29 · see citing works
“It has been shown that oxidative stress plays a significant role in the development of AD (Cioffi et al., 2019).”
Background
Drosophila as a model to explore secondary injury cascades after traumatic brain injury
Buhlman, L. M., Krishna, G., Jones, T. B., & Thomas, T. C. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112079 · Cited by 28 · see citing works
Potential of food-derived bioactive peptides in alleviation and prevention of Alzheimer's disease
Zhao, L., Li, D., Qi, X., Guan, K., Chen, H., Wang, R., & Ma, Y. (2022) · Food & Function · doi:10.1039/d2fo02278h · Cited by 29 · see citing works
Tau promotes oxidative stress-associated cycling neurons in S phase as a pro-survival mechanism: possible implication for Alzheimer's disease.
Denéchaud, M., Geurs, S., Comptdaer, T., Bégard, S., García-Núñez, A., Pechereau, L.-A., Bouillet, T., Vermeiren, Y., de Deyn, P., Perbet, R., et al. (2022) · Progress in neurobiology · doi:10.1016/j.pneurobio.2022.102386 · Cited by 28 · see citing works
Naturally Inspired Coumarin Derivatives in Alzheimer’s Disease Drug Discovery: Latest Advances and Current Challenges
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The Potential Mechanism and the Role of Antioxidants in Mitigating Oxidative Stress in Alzheimer’s Disease
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Background
Human salivary histatin 1 regulating IP3R1/GRP75/VDAC1 mediated mitochondrial-associated endoplasmic reticulum membranes (MAMs) inhibits cell senescence for diabetic wound repair
Xian, T., Liu, Y., Ye, Y., Peng, B., Huang, J., Liang, L., Zhang, J., Wu, H. B., & Lin, Z. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.09.046 · Cited by 25 · see citing works
CRISPR/Cas9 and iPSC-Based Therapeutic Approaches in Alzheimer’s Disease
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Nucleoside analogues: N-glycosylation methodologies, synthesis of antiviral and antitumor drugs and potential against drug-resistant bacteria and Alzheimer's disease
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Moliner, C., Cásedas, G., Barros, L., Finimundy, T. C., Rincón, C. G., & López, V. (2022) · Antioxidants · doi:10.3390/antiox11071244 · Cited by 21 · see citing works
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Apolipoprotein E ε4 modulates astrocyte neuronal support functions in the presence of amyloid‐β
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Background
The effect of ghrelin on antioxidant status in the rat’s model of Alzheimer's disease induced by amyloid-beta
Sarlaki, F., Shahsavari, Z., Goshadrou, F., Naseri, F., Keimasi, M., & Sirati‐Sabet, M. (2022) · Biomedicine · doi:10.37796/2211-8039.1341 · Cited by 20 · see citing works
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Innovative pathological network‐based multitarget approaches for Alzheimer's disease treatment
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Quinovic Acid Impedes Cholesterol Dyshomeostasis, Oxidative Stress, and Neurodegeneration in an Amyloid-β-Induced Mouse Model
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Background
Retracted
JWX-A0108, a positive allosteric modulator of α7 nAChR, attenuates cognitive deficits in APP/PS1 mice by suppressing NF-κB-mediated inflammation
Li, H., Gao, J., Chang, Y., Li, K., Wang, L., Ju, C., & Zhang, F. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107726 · Cited by 19 · see citing works
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Stein, J., Walkenfort, B., Cihankaya, H., Hasenberg, M., Bader, V., Winklhofer, K. F., Röderer, P., Matschke, J., Theiß, C., & Matschke, V. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6924251 · Cited by 19 · see citing works
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Background
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Suppression of tau‐induced phenotypes by vitamin E demonstrates the dissociation of oxidative stress and phosphorylation in mechanisms of tau toxicity
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24-Hydroxycholesterol Induces Tau Proteasome-Dependent Degradation via the SIRT1/PGC1α/Nrf2 Pathway: A Potential Mechanism to Counteract Alzheimer’s Disease
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[Retracted] The Effective Components, Core Targets, and Key Pathways of Ginseng against Alzheimer’s Disease
Wang, Y., & Liu, X. (2023) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2023/9935942 · Cited by 15 · see citing works
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Exercise Alleviates Behavioral Disorders but Shapes Brain Metabolism of APP/PS1 Mice in a Region- and Exercise-Specific Manner.
Ying, N., Luo, H., Li, B.-X., Gong, K.-Y., Shu, Q., Liang, F., Gao, H., Huang, T., & Zheng, H. (2023) · Journal of Proteome Research · doi:10.1021/acs.jproteome.2c00691 · Cited by 14 · see citing works
miR-277 targets the proapoptotic gene-hid to ameliorate Aβ42-mediated neurodegeneration in Alzheimer’s model
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Multifunctional Fluorescent Probes Unveiling Complex Pathways in Alzheimer’s Disease Pathogenesis
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A new K+channel-independent mechanism is involved in the antioxidant effect of XE-991 in an in vitro model of glucose metabolism impairment: implications for Alzheimer’s disease
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Authors: Cioffi, F., Adam, R. H. I., & Broersen, K.
Affiliations: University of Twente (NL)
Corresponding author: Broersen, Kerensa
ORCID: Broersen, Kerensa
Venue: Journal of Alzheimer s Disease
Publisher: SAGE Publications
Published: 2019-12-12
Volume: 72
Issue: 4
Pages: 981-1017
ISSN: 1387-2877 (ISSN-L)
1875-8908
DOI: 10.3233/jad-190863
PMC: PMC6971833
OpenAlex: W2984421981
Cited by: 204
References: 475
Citations by year: 2026: 17 · 2025: 30 · 2024: 36 · 2023: 36 · 2022: 28 · 2021: 36 · 2020: 21
FWCI: 2.50
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/4.0/ (unspecified)
Locations: Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
University of Twente Research Information (submittedVersion, cc-by-nc)
Funders: ZonMw (733050304)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: Alzheimer's disease, oxidative stress
MeSH terms: Alzheimer Disease, Animals, Brain, Humans, Amyloid beta-Peptides, tau Proteins, Reactive Oxygen Species, Oxidative Stress

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Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease

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