Redox proteomic analysis of carbonylated brain proteins in mild cognitive impairment and early Alzheimer’s disease
Open accessAbstract
Previous studies indicated increased levels of protein oxidation in brain from subjects with Alzheimer's disease (AD), raising the question of whether oxidative damage is a late effect of neurodegeneration or precedes and contributes to the pathogenesis of AD. Hence, in the present study we used a parallel proteomic approach to identify oxidatively modified proteins in inferior parietal lobule (IPL) from subjects with mild cognitive impairment (MCI) and early stage-AD (EAD). By comparing to age-matched controls, we reasoned that such analysis could help in understanding potential mechanisms involved in upstream processes in AD pathogenesis. We have identified four proteins that showed elevated levels of protein carbonyls: carbonic anhydrase II (CA II), heat shock protein 70 (Hsp70), mitogen-activated protein kinase I (MAPKI), and syntaxin binding protein I (SBP1) in MCI IPL. In EAD IPL we identified three proteins: phosphoglycerate mutase 1 (PM1), glial fibrillary acidic protein, and fructose bisphospate aldolase C (FBA-C). Our results imply that some of the common targets of protein carbonylation correlated with AD neuropathology and suggest a possible involvement of protein modifications in the AD progression.
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Both HSP70 and HSP90 are significantly carbonylated in MCI IPL.
“Both HSP70 and HSP90 are significantly carbonylated in MCI IPL [59,60]”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [59]
The Results report significantly increased carbonylation of Hsp70 in MCI inferior parietal lobule compared with age-matched controls (Table 3, page not specified). Hsp90 is not among the four significantly oxidized proteins identified there, so this source supports only the Hsp70 part of the claim. (LLM, conf=0.89)
Experimental — accuracy not yet measuredGS is oxidatively modified in both MCI and AD brain, likely resulting in the significantly decreased activity observed in AD brain.
“GS is also oxidatively modified in both MCI and AD brain [44,54,59], likely resulting in the significantly decreased activity observed in AD brain [133,134].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [59]
The Abstract lists the proteins found carbonylated in MCI and early AD brain, but does not include glutamine synthetase (GS). A search for “glutamine synthetase” and “GS” found only a References entry concerning AD brain, not a passage establishing GS oxidation in both MCI and AD. The decreased-activity clause has separate citations in the citing sentence. (LLM, conf=0.74)
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“MnSOD is oxidatively modified by HNE in early AD IPL, resulting in a significant decrease in enzyme activity [55] and is also oxidatively modified by HNE in late AD IPL [54].”
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“Of course, oxidative stress is strongly associated with amnestic MCI and AD [94–96], and Aβ is hypothesized to contribute to this oxidative stress [97].”
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- Authors
- Sultana, R., Perluigi, M., Newman, S. F., Pierce, W. M., Cini, C., Coccia, R., & Butterfield, D. A.
- Affiliations
- Department of Chemistry, University of Kentucky, Lexington, Kentucky.
- University of Kentucky (US)
- University of Louisville (US)
- Sapienza University of Rome (IT)
- Corresponding author
- Butterfield, D. Allan
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2010-02
- Volume
- 12
- Issue
- 3
- Pages
- 327-336
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC2821142
- OpenAlex
- W2076740879
- Cited by
- 125
- References
- 52
- Citations by year
- 2025: 5 · 2024: 10 · 2023: 6 · 2022: 3 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 6 · 2017: 2 · 2016: 7 · 2015: 10 · 2014: 7 · 2013: 12 · 2012: 8
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P01AG010836, P01AG005119, AG 10836, AG0 5119)
- 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
- protein carbonylation, oxidative protein damage, Alzheimer's disease, mild cognitive impairment, inferior parietal lobule, carbonic anhydrase II, HSP70, MAPK1, phosphoglycerate mutase 1, glial fibrillary acidic protein, redox proteomics, AD pathogenesis
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition Disorders, Female, Humans, Male, Oxidation-Reduction, Blotting, Western, Electrophoresis, Gel, Two-Dimensional, Case-Control Studies, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Proteomics, Immunoprecipitation, Protein Carbonylation
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