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4-Hydroxy-2-Nonenal, a Reactive Product of Lipid Peroxidation, and Neurodegenerative Diseases: A Toxic Combination Illuminated by Redox Proteomics Studies
Open accessAbstract
SIGNIFICANCE: Among different forms of oxidative stress, lipid peroxidation comprises the interaction of free radicals with polyunsaturated fatty acids, which in turn leads to the formation of highly reactive electrophilic aldehydes. Among these, the most abundant aldehydes are 4-hydroxy-2-nonenal (HNE) and malondialdehyde, while acrolein is the most reactive. HNE is considered a robust marker of oxidative stress and a toxic compound for several cell types. Proteins are particularly susceptible to modification caused by HNE, and adduct formation plays a critical role in multiple cellular processes. RECENT ADVANCES: With the outstanding progress of proteomics, the identification of putative biomarkers for neurodegenerative disorders has been the main focus of several studies and will continue to be a difficult task. CRITICAL ISSUES: The present review focuses on the role of lipid peroxidation, particularly of HNE-induced protein modification, in neurodegenerative diseases. By comparing results obtained in different neurodegenerative diseases, it may be possible to identify both similarities and specific differences in addition to better characterize selective neurodegenerative phenomena associated with protein dysfunction. Results obtained in our laboratory and others support the common deregulation of energy metabolism and mitochondrial function in neurodegeneration. FUTURE DIRECTIONS: Research towards a better understanding of the molecular mechanisms involved in neurodegeneration together with identification of specific targets of oxidative damage is urgently required. Redox proteomics will contribute to broaden the knowledge in regard to potential biomarkers for disease diagnosis and may also provide insight into damaged metabolic networks and potential targets for modulation of disease progression.
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“Peroxidation of polyunsaturated fatty acids in membrane lipids60 by ROS can generate highly reactive aldehydes, such as 4-hydroxynonenal, which irreversibly modify proteins by carbonylation.61,62”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [62]
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Metadata
- Authors
- Perluigi, M., Coccia, R., & Butterfield, D. A.
- Affiliations
- Department of Biochemical Sciences, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy.
- Sapienza University of Rome (IT)
- University of Kentucky (US)
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2012-12
- Volume
- 17
- Issue
- 11
- Pages
- 1590-1609
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC3449441
- OpenAlex
- W2073597659
- Cited by
- 229
- References
- 221
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 13 · 2023: 14 · 2022: 14 · 2021: 20 · 2020: 15 · 2019: 16 · 2018: 18 · 2017: 20 · 2016: 12 · 2015: 19 · 2014: 19 · 2013: 13 · 2012: 3
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- National Institutes of Health (AG-05119)
- National Institute on Aging (P01AG005119, R01AG029839, AG029839, AG0 5119)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- 4-hydroxynonenal, lipid peroxidation, neurodegenerative diseases, protein alkylation, protein adducts, oxidative stress, redox proteomics, biomarkers, mitochondrial dysfunction, energy metabolism, malondialdehyde, acrolein
- MeSH terms
- Aldehydes, Antioxidants, Fatty Acids, Unsaturated, Humans, Malondialdehyde, Oxidation-Reduction, Protein Processing, Post-Translational, Proteins, Lipid Peroxidation, Neurodegenerative Diseases
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