Low molar excess of 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote oligomerization of alpha-synuclein through different pathways
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Effect of 4-Hydroxy-2-Nonenal Modification on -Synuclein Aggregation
Several observations have implicated oxidative stress and aggregation of the presynaptic protein-synuclein in the pathogenesis of PD.-Synuclein has been shown to have affinity for unsaturated fatty acids and membranes enriched in PUFAs, which are especially sensitive to oxidation under conditions of oxidative stress. One of the most important products of lipid oxidation is 4-hydroxynonenal (H...
متن کاملSynaptosomal Toxicity and Nucleophilic Targets of 4-Hydroxy-2-Nonenal
4-Hydroxy-2-nonenal (HNE) is an aldehyde by-product of lipid peroxidation that is presumed to play a primary role in certain neuropathogenic states (e.g., Alzheimer disease, spinal cord trauma). Although the molecular mechanism of neurotoxicity is unknown, proteomic analyses (e.g., tandem mass spectrometry) have demonstrated that this soft electrophile preferentially forms Michael-type adducts ...
متن کاملTrans-4-oxo-2-nonenal potently alters mitochondrial function.
Alzheimer disease elevates lipid peroxidation in the brain and data indicate that the resulting lipid-aldehydes are pathological effectors of lipid peroxidation. The disposition of 4-substituted nonenals derived from arachidonate (20:4, n-6) and linoleate (18:2, n-6) oxidation is modulated by their protein adduction targets, their metabolism, and the nature of the 4-substitutent. Trans-4-oxo-2-...
متن کاملCytotoxicity and metabolism of 4 - hydroxy - 2 - nonenal and 2 - nonenal in H 202 - resistant cell lines
Toxic aldehydes, such as 4-hydroxy-2-nonenal (4HNE) and 2-nonenal (2NE), formed during lipid peroxidation have been isolated and implicated in the cytotoxic effects of oxidative stress. We have investigated the cytotoxicity and metabolism of 4HNE and 2NE in control (HA-1) cells and in two H202-resistant Chinese hamster fibroblast cell lines. The H202resistant cells were found to be significantl...
متن کاملCyclooxygenase-2 generates the endogenous mutagen trans-4-hydroxy-2-nonenal in Enterococcus faecalis-infected macrophages.
Infection of macrophages by the human intestinal commensal Enterococcus faecalis generates DNA damage and chromosomal instability in mammalian cells through bystander effects. These effects are characterized by clastogenesis and damage to mitotic spindles in target cells and are mediated, in part, by trans-4-hydroxy-2-nonenal (4-HNE). In this study, we investigated the role of COX and lipoxygen...
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ژورنال
عنوان ژورنال: Free Radical Biology and Medicine
سال: 2017
ISSN: 0891-5849
DOI: 10.1016/j.freeradbiomed.2017.07.004