Resveratrol Protects the Brain of Obese Mice from Oxidative Damage

Rege, Shraddha D.; Kumar, Shambhavi; Wilson, David; Tamura, Leslie; Geetha, Thangiah; Mathews, Suresh T.; Huggins, Kevin W.; Broderick, Tom L.; Babu, Jeganathan Ramesh

doi:10.1155/2013/419092

Cited by 51 publications

(29 citation statements)

References 46 publications

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“…In a STZ-treated rat model of diabetes, resveratrol slowed diabetes-induced neurodegeneration by decreasing both astrocytic activation and secretion of pro-inflammatory mediators like TNFα in the rat hippocampus (Jing et al, 2013). In another study examining oxidative nerve damage in lean and obese mice, resveratrol blocked the obesity-specific increases in LPO and upregulated antioxidant activity (Rege et al, 2013). Finally, in an earlier study of primary midbrain neuron-glia rat tissue cultures, resveratrol provided dopaminergic neuroprotection by inhibiting MGLA in lipopolysaccharide-induced neurotoxicity (Zhang et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Oxidative and nitrative stress in neurodegeneration

Cobb

Cole

2015

Neurobiology of Disease

241

180

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Aerobes require oxygen for metabolism and normal free radical formation. As a result, maintaining the redox homeostasis is essential for brain cell survival due to their high metabolic energy requirement to sustain electrochemical gradients, neurotransmitter release, and membrane lipid stability. Further, brain antioxidant levels are limited compared to other organs and less able to compensate for reactive oxygen and nitrogen species (ROS/RNS) generation which contribute oxidative/nitrative stress (OS/NS). Antioxidant treatments such as vitamin E, minocycline, and resveratrol mediate neuroprotection by prolonging the incidence of or reversing OS and NS conditions. Redox imbalance occurs when the antioxidant capacity is overwhelmed, consequently leading to activation of alternate pathways that remain quiescent under normal conditions. If OS/NS fails to lead to adaptation, tissue damage and injury ensue, resulting in cell death and/or disease. The progression of OS/NS-mediated neurodegeneration along with contributions from microglial activation, dopamine metabolism, and diabetes comprise a detailed interconnected pathway. This review proposes a significant role for OS/NS and more specifically, lipid peroxidation (LPO) and other lipid modifications, by triggering microglial activation to elicit a neuroinflammatory state potentiated by diabetes or abnormal dopamine metabolism. Subsequently, sustained stress in the neuroinflammatory state overwhelms cellular defenses and prompts neurotoxicity resulting in the onset or amplification of brain damage.

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Section: Discussionmentioning

confidence: 99%

Oxidative and nitrative stress in neurodegeneration

Cobb

Cole

2015

Neurobiology of Disease

241

180

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“…61 In the same line, RSV has been reported to normalize GSH or MDA levels in a rat model of spinal cord injury 62 or in the brain of obese mice. 63 Since the discovery of sirtuin-activating compounds such as RSV, 4 a rich controversy exists regarding the direct path via SIRT1 or via an indirect modus operandi of these compounds. 34 A recent and elegant study has shed some light on the debate and demonstrated that SIRT1 is directly activated by RSV, through an allosteric mechanism.…”

Section: Discussionmentioning

confidence: 99%

Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy

et al. 2015

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Oxidative stress and mitochondrial failure are prominent factors in the axonal degeneration process. In this study, we demonstrate that sirtuin 1 (SIRT1), a key regulator of the mitochondrial function, is impaired in the axonopathy and peroxisomal disease X-linked adrenoleukodystrophy (X-ALD). We have restored SIRT1 activity using a dual strategy of resveratrol treatment or by the moderate transgenic overexpression of SIRT1 in a X-ALD mouse model. Both strategies normalized redox homeostasis, mitochondrial respiration, bioenergetic failure, axonal degeneration and associated locomotor disabilities in the X-ALD mice. These results indicate that the reactivation of SIRT1 may be a valuable strategy to treat X-ALD and other axonopathies in which the control of redox and energetic homeostasis is impaired. Cell Death and Differentiation (2015) 22, 1742-1753 doi:10.1038/cdd.2015; published online 27 March 2015Sirtuins are highly conserved NAD + -dependent deacetylases with a critical impact on metabolic adaptive responses. In mammals, among the seven members of the sirtuin family (SIRT1-SIRT7), SIRT1 has been the most extensively characterized. 1 SIRT1 promotes the generation of new mitochondria through the activation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), which orchestrates the mitochondrial biogenesis program through the transcriptional activation of nuclear respiratory factors (NRF-1 and NRF-2) and mitochondrial transcription factor A (TFAM). 2 SIRT1 activity is finely regulated not only by gene expression and protein levels but also by posttranslational modifications, its oligomeric status, the interaction with the DBC1 and AROS proteins, and the levels of NAD + /NADH/NAM. 3 In addition, SIRT1 activity is modulated by several synthetic or natural molecules such as the polyphenol resveratrol (3,4',5-trihydroxystilbene: RSV). 4 The activation of SIRT1 by transgenic overexpression or pharmacologically with RSV has been shown to prevent the pathology in diseases commonly associated with mitochondrial dysfunction such as the metabolic syndrome and neurodegenerative disorders, 1,5,6 albeit recent findings cast doubts on the universal validity of the results. 7,8 Although prominent axonal pathology often precedes cell body loss in many neurodegenerative diseases, 9 the potential of SIRT1 activation in axonal degeneration has not been addressed in depth. In this work, we take advantage of the cellular and animal models of the rare monogenic neurodegenerative disease named X-linked adrenoleukodystrophy (X-ALD, (McKusick No.300100)) to evaluate the impact of SIRT1 function on axonal degeneration. X-ALD is the most prevalent peroxisomal disorder (minimum incidence 1:17 000 newborns), characterized by brain inflammatory demyelination and/or axonopathy of long tracts in spinal cords, adrenal insufficiency and a pathognomonic accumulation of very longchain fatty acids (VLCFA) in plasma and tissues, in particular hexacosanoic acid (C26:0). 10,11 The disease phenotypes range from adrenal ...

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“…All these compounds show excellent antioxidant activities and beneficial effects in preventing oxidative stress, mitochondrial dysfunction and inflammation in the experimental models of neurodegenerative disorders (Calabrese et al, 2012; Lee et al, 2015; Li et al, 2014; Nataraj et al, 2015; Rege et al, 2013; Singhal et al, 2013; Subash et al, 2014a, 2014b, 2015; Tapias et al, 2014; Vauzour, 2012; Vepsäläinen et al, 2013; Wang et al, 2014]. One of the well-known polyphenols is resveratrol (3, 5, 4’-trihydroxy-trans-stilbene) contained in red grapes and it has been shown to protect the brain from oxidative damage (Gacar et al, 2011).…”

Section: Translational Research Opportunities and Challengesmentioning

confidence: 99%

Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress

et al. 2016

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Mitochondria are important for providing cellular energy ATP through the oxidative phosphorylation pathway. They are also critical in regulating many cellular functions including the fatty acid oxidation, the metabolism of glutamate and urea, the anti-oxidant defense, and the apoptosis pathway. Mitochondria are an important source of reactive oxygen species leaked from the electron transport chain while they are susceptible to oxidative damage, leading to mitochondrial dysfunction and tissue injury. In fact, impaired mitochondrial function is commonly observed in many types of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, alcoholic dementia, brain ischemia-reperfusion related injury, and others, although many of these neurological disorders have unique etiological factors. Mitochondrial dysfunction under many pathological conditions is likely to be promoted by increased nitroxidative stress, which can stimulate post-translational modifications (PTMs) of mitochondrial proteins and/or oxidative damage to mitochondrial DNA and lipids. Furthermore, recent studies have demonstrated that various antioxidants, including naturally occurring flavonoids and polyphenols as well as synthetic compounds, can block the formation of reactive oxygen and/or nitrogen species, and thus ultimately prevent the PTMs of many proteins with improved disease conditions. Therefore, the present review is aimed to describe the recent research developments in the molecular mechanisms for mitochondrial dysfunction and tissue injury in neurodegenerative diseases and discuss translational research opportunities.

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Resveratrol Protects the Brain of Obese Mice from Oxidative Damage

Cited by 51 publications

References 46 publications

Oxidative and nitrative stress in neurodegeneration

Oxidative and nitrative stress in neurodegeneration

Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy

Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress

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