Lipid peroxidation and oxidative imbalance: early functional events in Alzheimer's disease

Praticò, Domenico; Sung, Syun

doi:10.3233/jad-2004-6209

Cited by 230Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAntioxidant Activity and Oxidative Stress

Lipid peroxidation and oxidative imbalance: early functional events in Alzheimer's disease

Praticò, Domenico, Sung, Syun·2004·Journal of Alzheimer s Disease

DOI 10.3233/jad-2004-6209

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Abstract

Alzheimer's disease (AD) is a growing public health problem worldwide. Clinically, AD is a progressive neurodegenerative disorder characterized by a global cognitive decline. Accumulating evidence indicates that reactive oxygen species-mediated reactions, particularly of neuronal lipids, are extensive in those AD brain areas directly involved in the disease processes. Traditional views claim that oxidative-mediated tissue injury in the AD brain is the result of neurodegeneration. In recent years, numerous investigations have pointed to the functional importance of oxidative imbalance as a crucial event in mediating AD pathogenesis. The availability of specific and sensitive markers to monitor in vivo oxidative stress, in combination with studies performed in living patients with clinical diagnosis of AD are helping us to elucidate these issues. The evidence we have accumulated so far clearly indicates that oxidative imbalance and subsequent oxidative stress are early events during the evolution of the disease, and secondary to specific mechanism(s) present in AD but not in other neurodegenerative diseases. These new concepts implicate that this phenomenon may play a more important role in AD pathogenesis than previously anticipated, and that any therapeutic intervention targeting oxidative stress should be initiated at the earliest possible stage of the disease.

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“the brain contains the high levels of polyunsaturated fatty acids (PUFAs) in its membrane rich architecture”
From NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer’s diseases (2021) · cites this paper as [54]
Lipid peroxidation could be a major feature of ferroptosis in Alzheimer's disease.
“lipid peroxidation could be a major feature of ferroptosis in AD”
From NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer’s diseases (2021) · cites this paper as [54]

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BackgroundInfluential
Redox active metals in neurodegenerative diseases
Acevedo, K. M., Masaldan, S., Opazo, C., & Bush, A. I. (2019) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-019-01731-9 · Cited by 101 · see citing works
Oxidative stress and hippocampal synaptic protein levels in elderly cognitively intact individuals with Alzheimer’s disease pathology
Scheff, S. W., Ansari, M. A., & Mufson, E. J. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.030 · Cited by 100 · see citing works
“…2001) and multiple studies have reported oxidative stress is significantly elevated in several brain regions of aMCI individuals (Ansari and Scheff, 2010,Ansari and Scheff, 2011,Butterfield, et al., 2006,Keller, et al., 2005,Markesbery, et al., 2005,Pratico and Sung, 2004,Williams, et al., 2006).”
Cinnamon and Its Metabolite Sodium Benzoate Attenuate the Activation of p21rac and Protect Memory and Learning in an Animal Model of Alzheimer’s Disease
Modi, K. K., Roy, A., Brahmachari, S., Rangasamy, S. B., & Pahan, K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130398 · Cited by 100 · see citing works
“Similarly, malondialdehyde and 4-hydroxynonenal, products of lipid peroxidation, are also increased in multiple brain regions of patients with AD or mild cognitive impairment (MCI) [6].”
Background
Neurodegenerative diseases linked to misfolded proteins and their therapeutic approaches: A review
Khanam, H., Ali, A., Asif, M., & Shamsuzzaman (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.08.006 · Cited by 100 · see citing works
The Pharmacological Properties and Therapeutic Use of Apomorphine
Ribarič, S. (2012) · Molecules · doi:10.3390/molecules17055289 · Cited by 98 · see citing works
“The hypothetical, AD-protective dopamine-independent effects of APO, supported by direct or indirect experimental evidence, are increased intracellular degradation of Aβ40 and Aβ42 [93], protection against oxidative stress [6,89–91,93,97,98] and a reduced oligomerisation and subsequent aggregation of Aβ42 into fibrils…”
Background
Design, synthesis and evaluation of scutellarein-O-alkylamines as multifunctional agents for the treatment of Alzheimer's disease
Sang, Z., Qiang, X., Li, Y., Yuan, W., Liu, Q., Shi, Y., Ang, W., Luo, Y., Tan, Z., & Deng, Y. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.02.063 · Cited by 93 · see citing works
Aluminum and other metals in Alzheimer's disease: A review of potential therapy with chelating agents
Domingo, J. L. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-102-315 · Cited by 91 · see citing works
“Oxidative stress is recognized as playing a major role in the pathogenesis of AD [85,86].”
The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics
Pritchard, S. M., Dolan, P. J., Vitkus, A., & Johnson, G. V. W. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01273.x · Cited by 89 · see citing works
Exploiting the lipoic acid structure in the search for novel multitarget ligands against Alzheimer’s disease
Rosini, M., Simoni, E., Bartolini, M., Tarozzi, A., Matera, R., Milelli, A., Hrelia, P., Andrisano, V., Bolognesi, M. L., & Melchiorre, C. (2011) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2011.09.001 · Cited by 90 · see citing works
Rhodiola roseaL. and Alzheimer's Disease: From Farm to Pharmacy
Nabavi, S. F., Braidy, N., Orhan, İ. E., Badiee, A., Daglia, M., & Nabavi, S. M. (2016) · Phytotherapy Research · doi:10.1002/ptr.5569 · Cited by 88 · see citing works
“As well, the activities of several endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase have been observed in both the central nervous system and peripheral nervous system tissues of AD patients (Pratico and Sung, 2004).”
Background
Aβ solubility and deposition during AD progression and in APP × PS-1 knock-in mice
Murphy, M. P., Beckett, T. L., Ding, Q., Patel, E., Markesbery, W. R., Clair, D. K. S., LeVine, H., & Keller, J. N. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.06.002 · Cited by 85 · see citing works
“…oxidative damage relative to control subjects (Butterfield et al., 2006; Ding et al., 2005; Keller et al., 2005; Markesbery et al., 2005), a process thatmay be a potential component of Aβ-induced neurotoxicity (Butterfield and Boyd-Kimball, 2004; Mattson, 2004; Pratico and Sung, 2004; Reddy, 2006).”
Background
The calcium–iron connection in ferroptosis-mediated neuronal death
Gleitze, S., Paula-Lima, A. C., Núñez, M. T., & Hidalgo, C. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.08.231 · Cited by 83 · see citing works
Altered central and blood glutathione in Alzheimer’s disease and mild cognitive impairment: a meta-analysis
Chen, J. J., Thiyagarajah, M. T., Song, J., Chen, C. C., Herrmann, N., Gallagher, D., Rapoport, M. J., Black, S. E., Ramirez, J., Andreazza, A. C., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-00961-5 · Cited by 88 · see citing works
Accelerated Amyloid Beta Pathogenesis by Bacterial Amyloid FapC
Javed, I., Zhang, Z., Adamčík, J., Andrikopoulos, N., Li, Y., Otzen, D. E., Lin, S., Mezzenga, R., Davis, T. P., Ding, F., et al. (2020) · Advanced Science · doi:10.1002/advs.202001299 · Cited by 82 · see citing works
Quantitative susceptibility mapping as an imaging biomarker for Alzheimer’s disease: The expectations and limitations
Uchida, Y., Kan, H., Sakurai, K., Oishi, K., & Matsukawa, N. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.938092 · Cited by 85 · see citing works
“Furthermore, lipid peroxidation and oxidative stress, hallmark features of ferroptosis, are considered an early event in AD pathogenesis (Praticò and Sung, 2004).”
Background
Oxidative Modification of Brain Proteins in Alzheimer's Disease: Perspective on Future Studies Based on Results of Redox Proteomics Studies
Rukhsana Sultana, A., & Butterfield, D. A. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129018 · Cited by 83 · see citing works
“[17–28].”
The protective role of plant biophenols in mechanisms of Alzheimer's disease
Omar, S. H., Scott, C., Hamlin, A. S., & Obied, H. K. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.02.016 · Cited by 82 · see citing works
“Altered composition of various phospholipids and elevated levels of lipid peroxidation products such as malondialdehyde, 4-hydroxy-2-trans-nonenal and isoprostanes are frequently described in AD patients [57, 137, 147-149].”
Background
Alpha-tocopherol quinone inhibits beta-amyloid aggregation and cytotoxicity, disaggregates preformed fibrils and decreases the production of reactive oxygen species, NO and inflammatory cytokines
Yang, S., Wang, W., Ling, T.-J., Feng, Y., Du, X., Zhang, X., Sun, X., Zhao, M., Xue, D., & Yang, Y. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.09.011 · Cited by 82 · see citing works
“ROS-induced injury was found in AD brains (Pratico and Sung, 2004).”
Background
Conformational Altered p53 as an Early Marker of Oxidative Stress in Alzheimer's Disease
Buizza, L., Cenini, G., Lanni, C., Ferrari‐Toninelli, G., Prandelli, C., Govoni, S. M., Buoso, E., Racchi, M., Barcikowska, M., Styczyńska, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029789 · Cited by 81 · see citing works
“Apart from the pathological hallmarks of the disease, which include accumulation of protein deposits in the brain as A b plaques and neurofibrillary tangles, AD brain exhibits constant evidence of ROS and RNS mediated injury [8].”
Tetrahydroxy stilbene glycoside ameliorates Alzheimer’s disease in APP/PS1 mice via glutathione peroxidase related ferroptosis
Gao, Y., Li, J., Wu, Q.-L., Wang, S., Yang, S., Li, X., Chen, N., Li, L., & Zhang, L. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108002 · Cited by 81 · see citing works
Emerging Mechanisms and Disease Implications of Ferroptosis: Potential Applications of Natural Products
Ge, C., Zhang, S., Mu, H., Shaojun, Z., Tan, Z., Huang, X., Chen, X., Zou, J., Zhu, Y., Dong, F., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.774957 · Cited by 77 · see citing works
“Neurodegeneration and Brain Injury A large body of evidence suggests that low levels of GSH/GSSG, elevated iron levels and lipid peroxidation are implicated in a variety of neurodegenerative diseases, along with abnormal levels of ferroptosis-associated modulators (Praticò and Sung, 2004; Belaidi and Bush, 2016).”
Background
Ferroptosis: A potential therapeutic target for neurodegenerative diseases
Vitalakumar, D., Sharma, A., & Flora, S. J. S. (2021) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22830 · Cited by 73 · see citing works
Ferroptosis and Tumor Drug Resistance: Current Status and Major Challenges
Nie, Z., Chen, M., Gao, Y., Huang, D., Cao, H., Peng, Y., Guo, N., Wang, F., & Zhang, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.879317 · Cited by 74 · see citing works
Isorhynchophylline Relieves Ferroptosis-Induced Nerve Damage after Intracerebral Hemorrhage Via miR-122-5p/TP53/SLC7A11 Pathway
Zhao, H., Li, X., Yang, L., Zhang, L., Jiang, X., Gao, W., Chen, P., Cheng, Y., Wang, F., & Liu, J. (2021) · Neurochemical Research · doi:10.1007/s11064-021-03320-2 · Cited by 70 · see citing works
Systemic Oxidative Stress in Older Patients with Mild Cognitive Impairment or Late Onset Alzheimer's Disease
Cervellati, C., Cremonini, E., Bosi, C., Magon, S., Zurlo, A., Bergamini, C. M., & Zuliani, G. (2013) · Current Alzheimer Research · doi:10.2174/1567205011310040003 · Cited by 70 · see citing works
CSF Biomarkers
Mattsson, N., Blennow, K., & Zetterberg, H. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04944.x · Cited by 68 · see citing works
Across the blood-brain barrier: Neurotherapeutic screening and characterization of naringenin as a novel CRMP-2 inhibitor in the treatment of Alzheimer's disease using bioinformatics and computational tools
Lawal, M., Olotu, F. A., & Soliman, M. E. S. (2018) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2018.05.012 · Cited by 66 · see citing works
Understanding Risk Factors for Alzheimer's Disease: Interplay of Neuroinflammation, Connexin-based Communication and Oxidative Stress
Quintanilla, R. A., Orellana, J. A., & Rommy von Bernhardi, M. (2012) · Archives of Medical Research · doi:10.1016/j.arcmed.2012.10.016 · Cited by 64 · see citing works
The neurobiology of isoprostanes and Alzheimer's disease
Praticò, D. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.01.009 · Cited by 65 · see citing works
Self-citation
The Neurotransmitter Noradrenaline Rescues Septal Cholinergic Neurons in Culture from Degeneration Caused by Low-Level Oxidative Stress
Traver, S., Salthun-Lassalle, B., Marien, M. R., Hirsch, É. C., Colpaert, F. C., & Michel, P. P. (2005) · Molecular Pharmacology · doi:10.1124/mol.104.007864 · Cited by 65 · see citing works
“, 2004) and ROS-mediated reactions (Casadesus et al., 2004; Pratico and Sung, 2004) are crucially involved in neurodegeneration in AD.”
Background
Lymphocyte mitochondria: toward identification of peripheral biomarkers in the progression of Alzheimer disease
Sultana, R., Baglioni, M., Cecchetti, R., Cai, J., Klein, J. B., Bastiani, P., Ruggiero, C., Mecocci, P., & Butterfield, D. A. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.08.001 · Cited by 64 · see citing works
Design, synthesis and evaluation of 4′-OH-flurbiprofen-chalcone hybrids as potential multifunctional agents for Alzheimer’s disease treatment
Cao, Z., Yang, J., Xu, R., Song, Q., Zhang, X., Liu, H., Qiang, X., Li, Y., Tan, Z., & Deng, Y. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2018.01.030 · Cited by 66 · see citing works
Serial CSF sampling in Alzheimer's disease: specific versus non-specific markers
Kester, M. I., Scheffer, P. G., Simmelink, M. J. A., Twaalfhoven, H. A. M., Verwey, N. A., Veerhuis, R., Twisk, J. W. R., Bouwman, F. H., Blankenstein, M. A., Scheltens, P., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.05.013 · Cited by 62 · see citing works
Understanding the mechanistic roles of environmental heavy metal stressors in regulating ferroptosis: adding new paradigms to the links with diseases
Sahoo, K., & Sharma, A. (2023) · APOPTOSIS · doi:10.1007/s10495-022-01806-0 · Cited by 64 · see citing works
“Characteristics of Alzheimer's disease, such as lipid peroxidation and iron dysregulation, are caused by iron-dependent cell death, which is known as ferroptosis [19, 95].”
Background
Rethinking Alzheimer's Disease Therapy: Are Mitochondria the Key?
Ankarcrona, M., Mangialasche, F., & Winblad, B. G. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100327 · Cited by 59 · see citing works
“Since individuals with MCI are at increased risk of developing dementia [88], the evidence of oxidative stress and nitrosative stress in subjects with MCI suggests that these as early events in cognitive decline.”
BackgroundInfluential
Cobalamin deficiency, hyperhomocysteinemia, and dementia
Werder (2010) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s6564 · Cited by 57 · see citing works

Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS
Sumowski, J. F., Rocca, M. A., Leavitt, V. M., Dackovic, J. R., Mesaroš, Š., Drulovic, J. S., DeLuca, J., & Filippi, M. (2014) · Neurology · doi:10.1212/wnl.0000000000000433 · Cited by 203 · see citing works
Tau and amyloid biomarkers modify the degree to which cognitive reserve and brain reserve predict cognitive decline
McKenzie, C., Bucks, R. S., Weinborn, M., et al. (2022) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617722000546 · Cited by 9 · see citing works
P3‐139: Crossword puzzles delay onset of accelerated cognitive decline in preclinical dementia, contributing to cognitive reserve
Hall, C. B., Lipton, R. B., & Verghese, J. (2009) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2009.04.1114
Openness to experience and cognitive functioning and decline in older adults: The mediating role of cognitive reserve
Montoliu, T., Zapater‐Fajarí, M., Hidalgo, V., & Salvador, A. (2023) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2023.108655 · Cited by 14 · see citing works
Does cognitive reserve shape cognitive decline?
Singh‐Manoux, A., Marmot, M. G., Glymour, M. M., Sabia, S., Mika Kivimaki, B., & Dugravot, A. (2011) · Annals of Neurology · doi:10.1002/ana.22391 · Cited by 170 · see citing works

Authors: Praticò, D., & Sung, S.
Affiliations: University of Pennsylvania (US)
Corresponding author: Praticò, Domenico
ORCID: Praticò, Domenico
Venue: Journal of Alzheimer s Disease
Publisher: SAGE Publications
Published: 2004-04-13
Volume: 6
Issue: 2
Pages: 171-175
ISSN: 1387-2877 (ISSN-L)
1875-8908
DOI: 10.3233/jad-2004-6209
OpenAlex: W1889306845
Cited by: 229
References: 0
Citations by year: 2026: 3 · 2025: 7 · 2024: 7 · 2023: 12 · 2022: 15 · 2021: 14 · 2020: 10 · 2019: 5 · 2018: 9 · 2017: 8 · 2016: 12 · 2015: 12 · 2014: 8 · 2013: 11 · 2012: 15
FWCI: 8.22
Type: journal article
Language: en
Open access: closed
Locations: Journal of Alzheimer s Disease (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute on Aging (P01AG011542, AG 11542)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords: Alzheimer's disease, lipid peroxidation
MeSH terms: Alzheimer Disease, Cognition Disorders, Frontal Lobe, Humans, Temporal Lobe, Time Factors, Lipid Peroxidation, Oxidative Stress, Isoprostanes

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Lipid peroxidation and oxidative imbalance: early functional events in Alzheimer's disease

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