ABSTRACT
There is ample evidence indicating that different reactive oxygen species (ROS), for example, superoxide, hydrogen peroxide, and hydroxyl and peroxyl radicals, are produced in cells under normal and pathological conditions (Sun et al. 2008). When the rate of ROS generation exceeds the capacity of antioxidant defense, there is consequential oxidative damage to DNA, proteins, and lipids. In the central nervous system (CNS), oxidative stress is implicated in mechanisms leading to neuronal cell injury in various pathological states. Recently, the term “nitrosative stress” has been used to indicate cellular damage elicited by reactive nitrogen species (RNS), which include nitric oxide (NO) and its congeners such as peroxynitrite and nitroxyl anion. Together, oxidative and nitrosative stresses are implicated in the pathology of many neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and stroke. The brain is particularly vulnerable to oxidative damage because it utilizes a large amount of oxygen for energy and has relatively low antioxidant defense enzymes, especially during aging. In addition, membranes in brain cells contain abnormally high proportions of polyunsaturated fatty acids (PUFAs). Of the different types of cells in the brain, neurons are especially vulnerable to insults by toxic compounds, and are sensitive to damage by ischemia/stroke, seizure, and other excitotoxic injury. Oxidative damage to lipids (lipid peroxidation) is associated with a progressive loss of membrane integrity, reduction of mitochondrial membrane potential, and increase in plasma membrane permeability to Ca2+. Oxidative damage to proteins leads to the formation of carbonyl and nitrosylated derivatives. Further, ROS damage to DNA results in nuclear condensation and altered gene expression. Therefore, oxidative stress is an important risk factor for
15.1 Introduction .......................................................................................................................... 315 15.2 Oxidative Stress and Neurodegenerative Disorders ............................................................. 316
15.2.1 Alzheimer’s Disease ................................................................................................. 316 15.2.1.1 Resveratrol and Grape Polyphenols ........................................................... 317 15.2.1.2 Curcumin (Diferuloylmethane) ................................................................. 318 15.2.1.3 Apocynin .................................................................................................... 319 15.2.1.4 Epigallocatechin-3-gallate (EGCG) ........................................................... 319
15.2.2 Parkinson’s Disease .................................................................................................. 320 15.2.3 Stroke ........................................................................................................................ 322
15.3 Integrated Signaling Mechanisms of Botanical Phenolics in Neurodegenerative Disorders ............................................................................................................................... 324
Acknowledgments .......................................................................................................................... 325 References ...................................................................................................................................... 325
neurodegeneration. In recent years, extensive effort has been devoted to developing novel strategies to overcome different types of insults in the brain (Sun et al. 2008; Farooqui and Farooqui 2009).
