4‐Hydroxynonenal‐Derived Advanced Lipid Peroxidation End Products Are Increased in Alzheimer's Disease

Journal of Neurochemistry (Impact Factor: 4.24). 04/1997; 68(5):2092 - 2097. DOI: 10.1046/j.1471-4159.1997.68052092.x

ABSTRACT Recent studies have demonstrated oxidative damage is one of the salient features of Alzheimer's disease (AD). In these studies, glycoxidation adduction to and direct oxidation of amino acid side chains have been demonstrated in the lesions and neurons of AD. To address whether lipid damage may also play an important pathogenic role, we raised rabbit antisera specific for the lysine-derived pyrrole adducts formed by lipid peroxidation-derived 4-hydroxynonenal (HNE). These antibodies were used in immunocytochemical evaluation of brain tissue from AD and age-matched control patients. HNE-pyrrole immunoreactivity not only was identified in about half of all neurofibrillary tangles, but was also evident in neurons lacking neurofibrillary tangles in the AD cases. In contrast, few senile plaques were labeled, and then only the dystrophic neurites were weakly stained, whereas the amyloid-β deposits were unlabeled. Age-matched controls showed only background HNE-pyrrole immunoreactivity in hippocampal or cortical neurons. In addition to providing further evidence that oxidative stress-related protein modification is a pervasive factor in AD, the known neurotoxicity of HNE suggests that lipid peroxidation may also play a role in the neuronal death in AD that underlies cognitive deficits.

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    • "These types of adducts, similar to what occur with the introduction of carbonyl groups, cause conformational changes of protein tridimensional structure that in turn affect its function. Protein bound lipid peroxidation products are commonly detected in samples by immunochemical methods or by spectrophotometry [14] [15] [16] [17]. Though lipid hydroperoxides form at membrane level, they are lipophilic and highly reactive and may initiate radical chain reactions on lipids and proteins in an adjacent cellular or organelle membrane [18]. "
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    ABSTRACT: Free radical-mediated damage to proteins is particularly important in aging and age-related neurodegenerative diseases, because in the majority of cases it is a non-reversible phenomenon that requires clearance systems for removal. Major consequences of protein oxidation are loss of protein function and the formation of large protein aggregates, which are often toxic to cells if allowed to accumulate. Deposition of aggregated, misfolded, and oxidized proteins may also result from the impairment of protein quality control (PQC) system, including protein unfolded response, proteasome, and autophagy. Perturbations of such components of the proteostasis network that provides a critical protective role against stress conditions are emerging as relevant factor in triggering neuronal death. In this outlook paper, we discuss the role of protein oxidation as a major contributing factor for the impairment of the PQC regulating protein folding, surveillance, and degradation. Recent studies from our group and from others aim to better understand the link between Down syndrome and Alzheimer's disease neuropathology. We propose oxidative stress and alteration of proteostasis network as a possible unifying mechanism triggering neurodegeneration.
    08/2014; 2014:14. DOI:10.1155/2014/527518
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    • ". HNE is a widely recognized lipid peroxidation end product and its involvement in neuronal loss in AD is demonstrated [53] [54] [55] [56] [57] [58]. Although the exact mechanism of the neurotoxicity due to HNE is still in debate, one idea is that its reaction with microtubule proteincysteine sulfhydryl groups would disrupt microtubule network [53]. "
    Dataset: C513
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    • "For example, acute severe lipid and protein peroxidation has been shown to be the cause of death when, despite appropriate treatment, people die from organophosphate poisoning [41]. Chronic lipid peroxidation may be a mechanism in carcinogenesis [42] and in the pathogenesis of Alzheimer's disease where the secondary oxidation product 4-hydroxynonenal (HNE) appears to have a role in both the formation of neurofibrillary tangles and neurotoxicity [43]. Oxidative stress further activates the NF-í µí¼…B pathway and increases production of proinflammatory cytokines [44]. "
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    ABSTRACT: Marine omega-3 rich oils are used by more than a third of American adults for a wide range of purported benefits including prevention of cardiovascular disease. These oils are highly prone to oxidation to lipid peroxides and other secondary oxidation products. Oxidized oils may have altered biological activity making them ineffective or harmful, though there is also evidence that some beneficial effects of marine oils could be mediated through lipid peroxides. To date, human clinical trials have not reported the oxidative status of the trial oil. This makes it impossible to understand the importance of oxidation to efficacy or harm. However, animal studies show that oxidized lipid products can cause harm. Oxidation of trial oils may be responsible for the conflicting omega-3 trial literature, including the prevention of cardiovascular disease. The oxidative state of an oil can be simply determined by the peroxide value and anisidine value assays. We recommend that all clinical trials investigating omega-3 harms or benefits report the results of these assays; this will enable better understanding of the benefits and harms of omega-3 and the clinical importance of oxidized supplements.
    04/2013; 2013:464921. DOI:10.1155/2013/464921
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