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Oxidative Stress and Neurodegenerative Diseases

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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 September 2014) | Viewed by 57920

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Special Issue Editor

Dr. Wenlan Liu

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Guest Editor

Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, MSC09 5360, Albuquerque, NM 87131-0001, USA
Interests: ischemic brain injury; neurodegenerative diseases; aging; oxidative stress; cell signaling pathways

Special Issue Information

Dear Colleagues,

Imbalance between generation and elimination of free radicals leads to oxidative stress and free radicals mediated tissue injury. Many lines of evidence suggest that oxidative stress plays an important role in neuronal loss in several CNS degenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, ischemic stroke, aging, and amyotrophic lateral sclerosis. Mitochondrial oxidative metabolism, NADPH oxidase, nitric oxide synthase, and phospholipids metabolism are potential sources of intracellular free radicals. It is well known that overproduction of free radicals produces damage to lipids, proteins and DNA and induces neuronal apoptosis or necrosis, however much work is needed to clarify the mechanisms by which excessive free radicals are generated in the diseased brain and the molecular mechanisms by which free radicals induce neuronal death. This Issue will allow publication of all aspects regarding oxidative stress and neurodegenerative diseases and of therapeutic strategies targeting free radical generation.

Prof. Dr. Wenlan Liu
Guest Editor

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Keywords

free radicals
oxidative stress
neurodegeneration
antioxidants

Published Papers (6 papers)

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Research

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1021 KiB

Open AccessArticle

A Cystine-Rich Whey Supplement (Immunocal^®) Delays Disease Onset and Prevents Spinal Cord Glutathione Depletion in the hSOD1^G93A Mouse Model of Amyotrophic Lateral Sclerosis

by Erika K. Ross, Aimee N. Winter, Heather M. Wilkins, Whitney A. Sumner, Nathan Duval, David Patterson and Daniel A. Linseman

Antioxidants 2014, 3(4), 843-865; https://doi.org/10.3390/antiox3040843 - 12 Dec 2014

Cited by 19 | Viewed by 11602

Abstract

Depletion of the endogenous antioxidant, glutathione (GSH), underlies progression of the devastating neurodegenerative disease, amyotrophic lateral sclerosis (ALS). Thus, strategies aimed at elevating GSH may yield new therapeutics for ALS. Here, we investigated the effects of a unique non-denatured whey protein supplement, Immunocal^®, in the transgenic Gly position 93 to Ala (G93A) mutant hSOD1 (hSOD1^G93A) mouse model of ALS. Immunocal^® is rich in the GSH precursor, cystine, and is therefore capable of bolstering GSH content. Transgenic hSOD1^G93A mice receiving Immunocal^® displayed a significant delay in disease onset compared to untreated hSOD1^G93A controls. Additionally, Immunocal^® treatment significantly decreased the rate of decline in grip strength and prevented disease-associated reductions in whole blood and spinal cord tissue GSH levels in end-stage hSOD1^G93A mice. However, Immunocal^® did not extend survival, likely due to its inability to preserve the mitochondrial GSH pool in spinal cord. Combination treatment with Immunocal^® and the anti-glutamatergic compound, riluzole, delayed disease onset and extended survival in hSOD1^G93A mice. These findings demonstrate that sustaining tissue GSH with Immunocal^® only modestly delays disease onset and slows the loss of skeletal muscle strength in hSOD1^G93A mice. Moreover, the inability of Immunocal^® to rescue mitochondrial GSH in spinal cord provides a possible mechanism for its lack of effect on survival and is a limiting factor in the potential utility of this supplement as a therapeutic for ALS. Full article

(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Diseases)

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337 KiB

Open AccessArticle

Antioxidant Activity of Grapevine Leaf Extracts against Oxidative Stress Induced by Carbon Tetrachloride in Cerebral Cortex, Hippocampus and Cerebellum of Rats

by Mariane Wohlenberg, Daniela Almeida, Liane Bokowski, Niara Medeiros, Fabiana Agostini, Cláudia Funchal and Caroline Dani

Antioxidants 2014, 3(2), 200-211; https://doi.org/10.3390/antiox3020200 - 02 Apr 2014

Cited by 12 | Viewed by 6708

Abstract

In recent years, it has become increasingly important to study the beneficial properties of derivatives of grapes and grapevine. The objective of this study was to determine the antioxidant activity of Vitis labrusca leaf extracts, comparing conventional and organic grapevines, in different brain areas of rats. We used male Wistar rats treated with grapevine leaf extracts for a period of 14 days, and on the 15th day, we administered in half of the rats, mineral oil and the other half, carbon tetrachloride (CCl₄). The animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were removed to assess oxidative stress parameters and the activity of antioxidant enzymes. Lipid peroxidation levels (TBARS) were unchanged. However, CCl₄ induced oxidative damage to proteins in all tissues studied, and this injury was prevented by both extracts. Superoxide dismutase (SOD) activity was increased by CCl₄ in the cerebral cortex and decreased in other tissues. However, CCl₄ increased catalase (CAT) activity in the cerebellum and decreased it in the cerebral cortex. The SOD/CAT ratio was restored in the cerebellum by both extracts and only in the cerebral cortex by the organic extract. Full article

(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Diseases)

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Review

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524 KiB

Open AccessReview

Role of Oxidative Stress in HIV-1-Associated Neurocognitive Disorder and Protection by Gene Delivery of Antioxidant Enzymes

by Jean-Pierre Louboutin and David Strayer

Antioxidants 2014, 3(4), 770-797; https://doi.org/10.3390/antiox3040770 - 18 Nov 2014

Cited by 27 | Viewed by 7549

Abstract

HIV encephalopathy covers a range of HIV-1-related brain dysfunction. In the Central Nervous System (CNS), it is largely impervious to Highly Active AntiRetroviral Therapy (HAART). As survival with chronic HIV-1 infection improves, the number of people harboring the virus in their CNS increases. Neurodegenerative and neuroinflammatory changes may continue despite the use of HAART. Neurons themselves are rarely infected by HIV-1, but HIV-1 infects resident microglia, periventricular macrophages, leading to increased production of cytokines and to release of HIV-1 proteins, the most likely neurotoxins, among which are the envelope glycoprotein gp120 and HIV-1 trans-acting protein Tat. Gp120 and Tat induce oxidative stress in the brain, leading to neuronal apoptosis/death. We review here the role of oxidative stress in animal models of HIV-1 Associated Neurocognitive Disorder (HAND) and in patients with HAND. Different therapeutic approaches, including clinical trials, have been used to mitigate oxidative stress in HAND. We used SV40 vectors for gene delivery of antioxidant enzymes, Cu/Zn superoxide dismutase (SOD1), or glutathione peroxidase (GPx1) into the rat caudate putamen (CP). Intracerebral injection of SV (SOD1) or SV (GPx1) protects neurons from apoptosis caused by subsequent inoculation of gp120 and Tat at the same location. Vector administration into the lateral ventricle or cisterna magna protects from intra-CP gp120-induced neurotoxicity comparably to intra-CP vector administration. These models should provide a better understanding of the pathogenesis of HIV-1 in the brain as well as offer new therapeutic avenues. Full article

(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Diseases)

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Open AccessReview

Assessing Antioxidant Capacity in Brain Tissue: Methodologies and Limitations in Neuroprotective Strategies

by Jennifer E. Slemmer and John T. Weber

Antioxidants 2014, 3(4), 636-648; https://doi.org/10.3390/antiox3040636 - 13 Oct 2014

Cited by 11 | Viewed by 6354

Abstract

The number of putative neuroprotective compounds with antioxidant activity described in the literature continues to grow. Although these compounds are validated using a variety of in vivo and in vitro techniques, they are often evaluated initially using in vitro cell culture techniques in order to establish toxicity and effective concentrations. Both in vivo and in vitro methodologies have their respective advantages and disadvantages, including, but not limited to, cost, time, use of resources and technical limitations. This review expands on the inherent benefits and drawbacks of in vitro and in vivo methods for assessing neuroprotection, especially in light of proper evaluation of compound efficacy and neural bioavailability. For example, in vivo studies can better evaluate the effects of protective compounds and/or its metabolites on various tissues, including the brain, in the whole animal, whereas in vitro studies can better discern the cellular and/or mechanistic effects of compounds. In particular, we aim to address the question of appropriate and accurate extrapolation of findings from in vitro experiment-where compounds are often directly applied to cellular extracts, potentially at higher concentrations than would ever cross the blood-brain barrier—to the more complex scenario of neuroprotection due to pharmacodynamics in vivo. Full article

(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Diseases)

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Open AccessReview

Friedreich’s Ataxia: A Neuronal Point of View on the Oxidative Stress Hypothesis

by Barbara Carletti and Fiorella Piemonte

Antioxidants 2014, 3(3), 592-603; https://doi.org/10.3390/antiox3030592 - 10 Sep 2014

Cited by 8 | Viewed by 6063

Abstract

A prominent feature of Friedreich’s ataxia (FRDA) is the neurodegeneration of the central and peripheral nervous systems, but little information is available about the mechanisms leading to neuronal damage in this pathology. Currently, no treatments delay, prevent, or reverse the inexorable decline that occurs in this condition. Evidence of oxidative damage has been demonstrated in Friedreich’s ataxia, and this damage has been proposed as the origin of the disease. Nevertheless, the role of oxidative stress in FRDA remains debatable. The lack of direct evidence of reactive oxygen species overproduction in FRDA cells and tissues and the failure of exogenous antioxidants to rescue FRDA phenotypes questions the role of oxidative stress in this pathology. For example, the antioxidant “idebenone” ameliorates cardiomyopathy in FRDA patients, but this therapy does not improve neurodegeneration. To date, no known pharmacological treatment with antioxidant properties cures or delays FRDA neuropathology. This review reports and discusses the evidence of oxidative stress in FRDA and focuses on the existing knowledge of the apparent ineffectiveness of antioxidants for the treatment of neuronal damage. Full article

(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Diseases)

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Open AccessReview

Melatonin Therapy in Patients with Alzheimer’s Disease

by Daniel P. Cardinali, Daniel E. Vigo, Natividad Olivar, María F. Vidal and Luis I. Brusco

Antioxidants 2014, 3(2), 245-277; https://doi.org/10.3390/antiox3020245 - 10 Apr 2014

Cited by 56 | Viewed by 18966

Abstract

Alzheimer’s disease (AD) is a major health problem and a growing recognition exists that efforts to prevent it must be undertaken by both governmental and non-governmental organizations. In this context, the pineal product, melatonin, has a promising significance because of its chronobiotic/cytoprotective properties potentially useful for a number of aspects of AD. One of the features of advancing age is the gradual decrease in circulating melatonin levels. A limited number of therapeutic trials have indicated that melatonin has a therapeutic value as a neuroprotective drug in the treatment of AD and minimal cognitive impairment (which may evolve to AD). Both in vitro and in vivo, melatonin prevented the neurodegeneration seen in experimental models of AD. For these effects to occur, doses of melatonin about two orders of magnitude higher than those required to affect sleep and circadian rhythmicity are needed. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects, which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50–100 mg/day are urgently needed to assess its therapeutic validity in neurodegenerative disorders such as AD. Full article

(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Diseases)

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