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Free Radical–Mediated Damage to Brain in Alzheimer’s Disease: Role of Acrolein and Preclinical Promise of Antioxidant Polyphenols

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Aging and Age-Related Disorders

Abstract

Brain aging is associated with accumulation of oxidation-induced damage, likely due to the imbalance between antioxidant defenses and intracellular generation of reactive oxygen species (ROS). Alzheimer’s disease (AD) is the most frequent neurodegenerative disease with multiple causes, and aging is considered as the major risk factor for the development of this disease. From early stages, oxidative damage is strongly implicated in the pathophysiology of this disorder. Lipid peroxidation generates various by-products such as F2α-isoprostane, 4-hydroxynonenal, malondialdehyde, and acrolein with the latter being the most reactive. In the neuroblastoma SK-N-SH cell line, our results show that acrolein can induce cell toxicity through a nonapoptotic pathway. Moreover, acrolein can alter the redox state by depleting glutathione levels. Considering the role of oxidative stress and the toxic effect of by-products of lipid oxidation, intake of compounds with antioxidant activities such as polyphenolic compounds may be beneficial in the prevention of AD. In this chapter, we will review the role of free radical–mediated damage in AD and in transgenic mouse models and present the main intracellular target of polyphenolic compounds underlying their potential neuroprotective effect.

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Authors and Affiliations

  1. INRS-Institut Armand-Frappier, Laval, QC, Canada

    Charles Ramassamy, Madeleine Arseneault & Dang Thanh Nam

  2. INAF, Laval University, Laval, Québec, Canada

    Charles Ramassamy

  3. Department of Medical Biology, Faculty of Medicine, Laval University, Laval, QC, Canada

    Charles Ramassamy

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  1. Charles Ramassamy
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  2. Madeleine Arseneault
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  3. Dang Thanh Nam
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Correspondence to Charles Ramassamy .

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  1. Center for Occupational & Environmental, Department of Medicine, University of California, Irvine, Room 320, Med Surge II, Irvine, 92697, California, USA

    Stephen Bondy

  2. New Jersey Medical School, Department of Neurology and Neuroscience, University of Medicine & Dentistry of Ne, South Orange Avenue 185, Newark, 07101, New Jersey, USA

    Kenneth Maiese

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Ramassamy, C., Arseneault, M., Nam, D.T. (2010). Free Radical–Mediated Damage to Brain in Alzheimer’s Disease: Role of Acrolein and Preclinical Promise of Antioxidant Polyphenols. In: Bondy, S., Maiese, K. (eds) Aging and Age-Related Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-602-3_21

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