Early Glycoxidation Damage in Brains from Down's Syndrome

Odetti, Patrizio; Ángelini, Giovanna; Dapino, Debora; Zaccheo, D; Garibaldi, Silvano; Dagna-Bricarelli, Francesca; Piombo, Giuseppe; Perry, George; Smith, Mark A.; Traverso, Nicola; Tabaton, Massimo

doi:10.1006/bbrc.1998.8186

Cited by 108 publications

(58 citation statements)

References 16 publications

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“…reaction). Supporting this, in addition to the evidence presented here, the secondary role of tau phosphorylation to oxidative stress is evident in sporadic AD [88], Down's syndrome [89] and even familial forms of AD [90]. According to some, the 'truth' might lie somewhere in the middle, such that phosphorylated tau is toxic (as considered in the classic concept) but its uptake into NFTs prevents it from causing harm.…”

Section: Discussionsupporting

confidence: 70%

Tau phosphorylation in Alzheimer's disease: pathogen or protector?

Lee

Perry

Moreira

et al. 2005

Trends in Molecular Medicine

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213

123

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Section: Discussionsupporting

confidence: 70%

Tau phosphorylation in Alzheimer's disease: pathogen or protector?

Lee

Perry

Moreira

et al. 2005

Trends in Molecular Medicine

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213

123

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“…Elevated levels of thiobarbituric acid reactive substances were demonstrated in the cortex from DS fetal brain compared with controls (139). Further, increased levels of isoprostane (8,12-iso-iPF2a) have been measured in urine samples from adults with DS (160).…”

Section: Down Syndromementioning

confidence: 99%

4-Hydroxy-2-Nonenal, a Reactive Product of Lipid Peroxidation, and Neurodegenerative Diseases: A Toxic Combination Illuminated by Redox Proteomics Studies

Perluigi

Coccia

Butterfield

2012

Antioxidants & Redox Signaling

190

133

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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. Antioxid. Redox Signal. 17, 1590-1609.

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“…Elevated OS has been demonstrated in the brains of DS patients, as indexed by increased levels of thiobarbituric acid reactive substances (TBARs), total protein carbonyls and advanced glycation end products in the cortex from DS fetal brain compared with controls [11], and a marked accumulation of 8-hydroxy-2-deoxyguanosine (8OHdG), oxidized proteins and nitrotyrosine in the cytoplasm of cerebral neurons in DS [12]. Elevated levels of isoprostane 8,12-iso-iPF2α (iPF2α), a specific marker of lipid peroxidation, have been demonstrated in living adults with DS [13].…”

Section: Is Os the Bridge Between Ds And Alzheimer's Disease?mentioning

confidence: 99%