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

Abstract

Brain aging is associated with accumulation of oxidation-induced damage,likely due to the imbalance between antioxidant defenses andintracellular generation of reactive oxygen species (ROS). Alzheimer'sdisease (AD) is the most frequent neurodegenerative disease withmultiple causes, and aging is considered as the major risk factor forthe development of this disease. From early stages, oxidative damage isstrongly implicated in the pathophysiology of this disorder. Lipidperoxidation generates various by-products such as Fa alpha-isoprostane,4-hydroxynonenal, malondialdehyde, and acrolein with the latter beingthe most reactive. In the neuroblastoma SK-N-SH cell line, our resultsshow that acrolein can induce cell toxicity through a nonapoptoticpathway. Moreover, acrolein can alter the redox state by depletingglutathione levels. Considering the role of oxidative stress and thetoxic effect of by-products of lipid oxidation, intake of compounds withantioxidant activities such as polyphenolic compounds may he beneficialin the prevention of AD. In this chapter, we will review the role offree radical mediated damage in AD and in transgenic mouse models andpresent the main intracellular target of polyphenolic compoundsunderlying their potential neuroprotective effect.