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Redox Homeostasis and Cellular Stress Response in Aging and Neurodegeneration

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Free Radicals and Antioxidant Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 610))

Abstract

Decreased expression and/or activity of antioxidant proteins leads to oxidative stress, accelerated aging, and neurodegeneration. While overwhelming levels and uncontrolled/dysregulated actions of reactive oxygen species (ROS) lead to deleterious effects, tighter regulation of those plays an important role in cell signaling. Mutations causing protein misfolding and the overload of toxic products derived from the free radical oxidation of polyunsaturated fatty acids, cholesterol, and glucose contribute to the disruption of the cellular redox homeostasis. Collectively or individually, these effects create pro-oxidant conditions in cells. Oxidative stress can induce neuronal damage, modulate intracellular signaling, and can ultimately lead to neuronal death by apoptosis or necrosis. Emerging evidence indicates that homocysteine (Hcy), a non-protein amino acid naturally present in the plasma, is implicated as a risk factor for numerous diseases. In particular, increased levels of circulating Hcy have been recognized as an independent risk factor for the development of vascular disease(s). Recent findings emphasize a relationship between elevated Hcy levels and neurodegeneration, which can be observed in Alzheimer’s and Parkinson’s diseases. An integrated response exists in the brain to detect and control diverse forms of stress. This is accomplished by a complex network of the so-called longevity assurance processes, which are controlled by several genes termed “vitagenes.” Among these, the heat-shock proteins (HSPs) form a highly conserved system that is responsible for the preservation and repair of the correct protein conformation. Recent studies have shown that the heat-shock response (HSR) contributes to cytoprotection in a number of human diseases including inflammation, cancer, aging, and neurodegenerative disorders. Given the broad cytoprotective properties of the HSR, interest mounts currently among investigators toward discovering and developing pharmacological agents capable of inducing HSR. l-Acetylcarnitine (LAC) is proposed as a therapeutic agent for several neurodegenerative disorders and also current evidence suggests that the compound may play a critical role in the modulation of cellular stress response in health and disease conditions. Here, we review the emerging salient concepts highlighting the pathways of neurodegeneration and the role of LAC in modulating the redox-dependent mechanisms responsible for the upregulation of vitagenes in brain that leads to the enhancement of stress tolerance in brain.

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Authors and Affiliations

  1. Department of Chemistry, Biochemistry & Molecular Biology Section, Faculty of Medicine, University of Catania, Catania, Italy

    Vittorio Calabrese, Carolin Cornelius & A.M. Giuffrida Stella

  2. Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy

    Cesare Mancuso

  3. Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy

    Riccardo Lentile

  4. Department of Chemistry, Sanders-Brown Center on Aging and Center of Membrane Sciences, University of Kentucky, Lexington, KY, USA

    D. Allan Butterfield

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  1. Vittorio Calabrese
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  2. Carolin Cornelius
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  3. Cesare Mancuso
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  4. Riccardo Lentile
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  5. A.M. Giuffrida Stella
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  6. D. Allan Butterfield
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Editors and Affiliations

  1. A& M College, Southern University &, James L. Hunt Street, Baton Rouge, 70813, U.S.A.

    Rao M. Uppu

  2. School of Medicine, Tulane University, Tulane Ave. 1430, New Orleans, 70112, U.S.A.

    Subramanyam N. Murthy

  3. Biodynamics Inst., Louisiana State University, Baton Rouge, 70808, U.S.A.

    William A. Pryor

  4. Dorothy M. Davis Heart &, Ohio State University, West 12th Ave. 473, Columbus, 43210, U.S.A.

    Narasimham L. Parinandi

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Calabrese, V., Cornelius, C., Mancuso, C., Lentile, R., Stella, A.G., Butterfield, D.A. (2010). Redox Homeostasis and Cellular Stress Response in Aging and Neurodegeneration. In: Uppu, R., Murthy, S., Pryor, W., Parinandi, N. (eds) Free Radicals and Antioxidant Protocols. Methods in Molecular Biology, vol 610. Humana Press. https://doi.org/10.1007/978-1-60327-029-8_17

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