Oxidative Nerve Cell Death in Alzheimers Disease and Stroke: Antioxidants as Neuroprotective Compounds
-
C. Behl
Abstract
Many neurodegenerative disorders and syndromes are associated with an excessive generation of reactive oxygen species (ROS) and oxidative stress. The pathways to nerve cell death induced by diverse potential neurotoxins such as peptides, excitatory amino acids, cytokines or synthetic drugs commonly share oxidative downstream processes, which can cause either an acute oxidative destruction or activate secondary events leading to apoptosis. The pathophysiological role of ROS has been intensively studied in in vitro and in vivo models of chronic neurodegenerative diseases such as Alzheimers disease (AD) and of syndromes associated with rapid nerve cell loss as occuring in stroke. In AD, oxidative neuronal cell dysfunction and cell death caused by protofibrils and aggregates of the ADassociated amyloid β protein (Aβ) may causally contribute to pathogenesis and progression. ROS and reactive nitrogen species also take part in the complex cascade of events and the detrimental effects occuring during ischemia and reperfusion in stroke. Direct antioxidants such as chainbreaking free radical scavengers can prevent oxidative nerve cell death. Although there is ample experimental evidence demonstrating neuroprotective activities of direct antioxidants in vitro, the clinical evidence for antioxidant compounds to act as protective drugs is relatively scarce. Here, the neuroprotective potential of antioxidant phenolic structures including αtocopherol (vitamin E) and 17βestradiol (estrogen) in vitro is summarized. In addition, the antioxidant and cytoprotective activities of lipophilic tyrosine and tryptophancontaining structures are discussed. Finally, an outlook is given on the neuroprotective potential of aromatic amines and imines, which may comprise novel lead structures for antioxidant drug design.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Highlight: Oxidative Stress
- Highlight: Oxidative Stress
- Peroxiredoxins
- 15-Lipoxygenase-1: A Prooxidant Enzyme
- Reactive Sulfur Species: An Emerging Concept in Oxidative Stress
- The Pathobiochemistry of Nitrogen Dioxide
- Nitric Oxide and Peroxynitrite Interactions with Mitochondria
- Nitric Oxide and Cell Signaling Pathways in Mitochondrial-Dependent Apoptosis
- Fatty Acid Oxidation and Signaling in Apoptosis
- Oxidant-Induced Signaling: Effects of Peroxynitrite and Singlet Oxygen
- The 80th Anniversary of Vitamin E: Beyond Its Antioxidant Properties
- Role of Endogenous Oxidative DNA Damage in Carcinogenesis: What Can We Learn from Repair-Deficient Mice?
- Mammalian Cell Injury Induced by Hypothermia the Emerging Role for Reactive Oxygen Species
- The Chelatable Iron Pool in Living Cells: A Methodically Defined Quantity
- Dietary Flavonoids as Potential Neuroprotectants
- Oxidative Nerve Cell Death in Alzheimers Disease and Stroke: Antioxidants as Neuroprotective Compounds
- A2E and Blue Light in the Retina: The Paradigm of Age-Related Macular Degeneration
- Interactions of Nitric Oxide and Peroxynitrite with Low-Density Lipoprotein
- Non-Antioxidant Properties of Carotenoids
- Proteolytic Response to Oxidative Stress in Mammalian Cells
- Neurospora crassa Catalases, Singlet Oxygen and Cell Differentiation
- The Cellular Hydration State: A Critical Determinant for Cell Death and Survival
- Redox Regulation of Stress Signals: Possible Roles of Dendritic Stellate TRX Producer Cells (DST Cell Types)
- Oxidative Stress, Spermatogenesis and Fertility
- Postprandial Oxidative Stress
- [18O]-Labeled Singlet Oxygen as a Tool for Mechanistic Studies of 8-Oxo-7,8-Dihydroguanine Oxidative Damage: Detection of Spiroiminodihydantoin, Imidazolone and Oxazolone Derivatives
- The Specificity of Lipoxygenase-Catalyzed Lipid Peroxidation and the Effects of Radical- Scavenging Antioxidants
- Human Neutrophils Oxidize Low-Density Lipoprotein by a Hypochlorous Acid- Dependent Mechanism: The Role of Vitamin C
- Perturbation of Lipid Metabolism by Linoleic Acid Hydroperoxide in CaCo-2 Cells
- Irreversible Thiol Oxidation in Carbonic Anhydrase III: Protection by S-Glutathiolation and Detection in Aging Rats
- Green Tea Extract Protects against Early Alcohol-Induced Liver Injury in Rats
- Comparing β-Carotene, Vitamin E and Nitric Oxide as Membrane Antioxidants
- Induction of Thioredoxin Reductase Gene Expression by Peroxynitrite in Human Umbilical Vein Endothelial Cells
- Activation of c-Jun N-Terminal Kinase and Apoptosis in Endothelial Cells Mediated by Endogenous Generation of Hydrogen Peroxide
- Detection of Poly(ADP-Ribose) by Immunocytochemistry: A Sensitive New Method for the Early Identification of UVB- and H2O2-Induced Apoptosis in Keratinocytes
- Efficacy of HOCl Scavenging by Sulfur- Containing Compounds: Antioxidant Activity of Glutathione Disulfide?
- Cysteine Supplementation Prevents Unweighting-Induced Ubiquitination in Association with Redox Regulation in Rat Skeletal Muscle
Articles in the same Issue
- Highlight: Oxidative Stress
- Highlight: Oxidative Stress
- Peroxiredoxins
- 15-Lipoxygenase-1: A Prooxidant Enzyme
- Reactive Sulfur Species: An Emerging Concept in Oxidative Stress
- The Pathobiochemistry of Nitrogen Dioxide
- Nitric Oxide and Peroxynitrite Interactions with Mitochondria
- Nitric Oxide and Cell Signaling Pathways in Mitochondrial-Dependent Apoptosis
- Fatty Acid Oxidation and Signaling in Apoptosis
- Oxidant-Induced Signaling: Effects of Peroxynitrite and Singlet Oxygen
- The 80th Anniversary of Vitamin E: Beyond Its Antioxidant Properties
- Role of Endogenous Oxidative DNA Damage in Carcinogenesis: What Can We Learn from Repair-Deficient Mice?
- Mammalian Cell Injury Induced by Hypothermia the Emerging Role for Reactive Oxygen Species
- The Chelatable Iron Pool in Living Cells: A Methodically Defined Quantity
- Dietary Flavonoids as Potential Neuroprotectants
- Oxidative Nerve Cell Death in Alzheimers Disease and Stroke: Antioxidants as Neuroprotective Compounds
- A2E and Blue Light in the Retina: The Paradigm of Age-Related Macular Degeneration
- Interactions of Nitric Oxide and Peroxynitrite with Low-Density Lipoprotein
- Non-Antioxidant Properties of Carotenoids
- Proteolytic Response to Oxidative Stress in Mammalian Cells
- Neurospora crassa Catalases, Singlet Oxygen and Cell Differentiation
- The Cellular Hydration State: A Critical Determinant for Cell Death and Survival
- Redox Regulation of Stress Signals: Possible Roles of Dendritic Stellate TRX Producer Cells (DST Cell Types)
- Oxidative Stress, Spermatogenesis and Fertility
- Postprandial Oxidative Stress
- [18O]-Labeled Singlet Oxygen as a Tool for Mechanistic Studies of 8-Oxo-7,8-Dihydroguanine Oxidative Damage: Detection of Spiroiminodihydantoin, Imidazolone and Oxazolone Derivatives
- The Specificity of Lipoxygenase-Catalyzed Lipid Peroxidation and the Effects of Radical- Scavenging Antioxidants
- Human Neutrophils Oxidize Low-Density Lipoprotein by a Hypochlorous Acid- Dependent Mechanism: The Role of Vitamin C
- Perturbation of Lipid Metabolism by Linoleic Acid Hydroperoxide in CaCo-2 Cells
- Irreversible Thiol Oxidation in Carbonic Anhydrase III: Protection by S-Glutathiolation and Detection in Aging Rats
- Green Tea Extract Protects against Early Alcohol-Induced Liver Injury in Rats
- Comparing β-Carotene, Vitamin E and Nitric Oxide as Membrane Antioxidants
- Induction of Thioredoxin Reductase Gene Expression by Peroxynitrite in Human Umbilical Vein Endothelial Cells
- Activation of c-Jun N-Terminal Kinase and Apoptosis in Endothelial Cells Mediated by Endogenous Generation of Hydrogen Peroxide
- Detection of Poly(ADP-Ribose) by Immunocytochemistry: A Sensitive New Method for the Early Identification of UVB- and H2O2-Induced Apoptosis in Keratinocytes
- Efficacy of HOCl Scavenging by Sulfur- Containing Compounds: Antioxidant Activity of Glutathione Disulfide?
- Cysteine Supplementation Prevents Unweighting-Induced Ubiquitination in Association with Redox Regulation in Rat Skeletal Muscle
