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      Neuroprotective Properties of the Marine Carotenoid Astaxanthin and Omega-3 Fatty Acids, and Perspectives for the Natural Combination of Both in Krill Oil

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          Abstract

          The consumption of marine fishes and general seafood has long been recommended by several medical authorities as a long-term nutritional intervention to preserve mental health, hinder neurodegenerative processes, and sustain cognitive capacities in humans. Most of the neurological benefits provided by frequent seafood consumption comes from adequate uptake of omega-3 and omega-6 polyunsaturated fatty acids, n-3/ n-6 PUFAs, and antioxidants. Optimal n-3/ n-6 PUFAs ratios allow efficient inflammatory responses that prevent the initiation and progression of many neurological disorders. Moreover, interesting in vivo and clinical studies with the marine antioxidant carotenoid astaxanthin (present in salmon, shrimp, and lobster) have shown promising results against free radical-promoted neurodegenerative processes and cognition loss. This review presents the state-of-the-art applications of n-3/ n-6 PUFAs and astaxanthin as nutraceuticals against neurodegenerative diseases associated with exacerbated oxidative stress in CNS. The fundamental “neurohormesis” principle is discussed throughout this paper. Finally, new perspectives for the application of a natural combination of the aforementioned anti-inflammatory and antioxidant agents (found in krill oil) are also presented herewith.

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          Most cited references137

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          Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple.

          Redox state is a term used widely in the research field of free radicals and oxidative stress. Unfortunately, it is used as a general term referring to relative changes that are not well defined or quantitated. In this review we provide a definition for the redox environment of biological fluids, cell organelles, cells, or tissue. We illustrate how the reduction potential of various redox couples can be estimated with the Nernst equation and show how pH and the concentrations of the species comprising different redox couples influence the reduction potential. We discuss how the redox state of the glutathione disulfide-glutathione couple (GSSG/2GSH) can serve as an important indicator of redox environment. There are many redox couples in a cell that work together to maintain the redox environment; the GSSG/2GSH couple is the most abundant redox couple in a cell. Changes of the half-cell reduction potential (E(hc)) of the GSSG/2GSH couple appear to correlate with the biological status of the cell: proliferation E(hc) approximately -240 mV; differentiation E(hc) approximately -200 mV; or apoptosis E(hc) approximately -170 mV. These estimates can be used to more fully understand the redox biochemistry that results from oxidative stress. These are the first steps toward a new quantitative biology, which hopefully will provide a rationale and understanding of the cellular mechanisms associated with cell growth and development, signaling, and reductive or oxidative stress.
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            Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders.

            Despite the capacity of chaperones and other homeostatic components to restore folding equilibrium, cells appear poorly adapted for chronic oxidative stress that increases in cancer and in metabolic and neurodegenerative diseases. Modulation of endogenous cellular defense mechanisms represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in neurodegeneration. This article introduces the concept of hormesis and its applications to the field of neuroprotection. It is argued that the hormetic dose response provides the central underpinning of neuroprotective responses, providing a framework for explaining the common quantitative features of their dose-response relationships, their mechanistic foundations, and their relationship to the concept of biological plasticity, as well as providing a key insight for improving the accuracy of the therapeutic dose of pharmaceutical agents within the highly heterogeneous human population. This article describes in mechanistic detail how hormetic dose responses are mediated for endogenous cellular defense pathways, including sirtuin and Nrf2 and related pathways that integrate adaptive stress responses in the prevention of neurodegenerative diseases. Particular attention is given to the emerging role of nitric oxide, carbon monoxide, and hydrogen sulfide gases in hormetic-based neuroprotection and their relationship to membrane radical dynamics and mitochondrial redox signaling.
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              Activation of microglial cells by beta-amyloid protein and interferon-gamma.

              Alzheimer's disease is the most common cause of progressive intellectual failure. The lesions that develop, called senile plaques, are extracellular deposits principally composed of insoluble aggregates of beta-amyloid protein (A beta), infiltrated by reactive microglia and astrocytes. Although A beta, and a portion of it, the fragment 25-35 (A beta (25-35)), have been shown to exert a direct toxic effect on neurons, the role of microglia in such neuronal injury remains unclear. Here we report a synergistic effect between A beta and interferon-gamma (IFN-gamma) in triggering the production of reactive nitrogen intermediates and tumour-necrosis factor-alpha (TNF-alpha) from microglia. Furthermore, using co-culture experiments, we show that activation of microglia with IFN-gamma and A beta leads to neuronal cell injury in vitro. These findings suggest that A beta and IFN-gamma activate microglia to produce reactive nitrogen intermediates and TNF-alpha, and this may have a role in the pathogenesis of neuronal degeneration observed in ageing and Alzheimer's disease.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                24 March 2014
                March 2014
                : 6
                : 3
                : 1293-1317
                Affiliations
                [1 ]Institute of Physical Activity and Sports Science (ICAFE), Cruzeiro do Sul University, 01506-000 São Paulo, Brazil; E-Mail: sandra.poppe@ 123456cruzeirodosul.edu.br
                [2 ]Graduation Program in Health Sciences, Cruzeiro do Sul University, 01506-000 São Paulo, Brazil; E-Mail: eduardo.bondan@ 123456cruzeirodosul.edu.br
                [3 ]Department of Veterinary Medicine, University Paulista (UNIP), 01506-000 São Paulo, Brazil
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: marcelo.barros@ 123456cruzeirodosul.edu.br ; Tel.: +55-11-3385-3103.
                Article
                nutrients-06-01293
                10.3390/nu6031293
                3967194
                24667135
                8c8ebe35-68ce-45fe-97e4-343a3869786c
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 31 October 2013
                : 24 February 2014
                : 03 March 2014
                Categories
                Review

                Nutrition & Dietetics
                seafood,neurodegenerative disorders,antioxidant,anti-inflammatory,cognition,oxidative stress,natural products,alzheimer’s,parkinson’s,hormesis

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