Oxidative Stress and Age-Related Neurodegeneration

by Luo; Yuan

• ISBN13: 9780849337253
• ISBN10: 0849337259
• eBook ISBN(s): 9781040201282
• Edition: 1st
• Format: Hardcover
• Copyright: 2005-11-21
• Publisher: CRC Press
• More Book Details

Summary

Despite the progress being made by researchers, Alzheimer's disease, along with other age-related neurodegenerative disorders, continues to exact a tremendous toll on our society. However, we are beginning to see a relationship that ties degenerative disorders to oxidative stress and lifestyle, suggesting the possibility for prevention and intervention through changes of individual habits, especially with regard to diet.Oxidative Stress and Age-Related Neurodegeneration brings together expert researchers involved with recent developments across a variety of fields. In looking at causation, prevention, and therapy, they offer contributions addressing these questions:· What similarities and differences exist between normal aging and disease-related neurodegeneration in terms of susceptibility to and effects of oxidative stress?· How can oxidative stress or its effects be attenuated?· Do antioxidants prevent or slow the progress of the disease?· Is there any role for natural micronutrients in the attenuation of oxidative stress and prevention of age-related neurodegeneration?Some chapters look at the various ways research is getting to the core of neurodegenerative disease, including the use of proteomics, comparisons to related diseases, and examinations at the cellular and molecular levels. Other chapters focus on specific antioxidants and nutrients cited as being impactful, such as those found in Gingko biloba, green tea, blueberries, and grape seed extract.Researchers in academia, industry, and clinical medicine, as well as students and scholars will find use for this timely collection, either as an introduction to our current understanding of neurodegeneration or as a reference for further research. Clinicians will also benefit, as this book explains the basis for many of the latest approaches to prevention and therapy.

Table of Contents

Proteomics Identification of Oxidatively Modified Proteins in the Alzheimer's Disease Brain and Models Thereof: Insights into Potential Mechanisms of Neurodegeneration	1	(26)
D. Allan Butterfield
H. Fai Poon
Rukhsana Sultana
Introduction	2	(1)
Methodology	3	(5)
Alzheimer's Disease Brain Tissue	3	(1)
Cholinergic Animal Model	4	(1)
Caenorhabditis Elegans	4	(1)
Senescence-Accelerated Mice Prone 8 (SAMP8)	4	(1)
Two-Dimensional Polyacrylamide Gel Electrophoresis	4	(2)
Mass Spectrometry and Database Searching	6	(2)
Proteomics Studies on Oxidatively Modified Proteins in the Alzheimer's Disease Brain	8	(3)
Proteins Involved in Energy Metabolism	8	(1)
Proteins Involved in Glutamate Reuptake or Conversion	9	(1)
Altered Synaptic Function	9	(1)
Proteasomal Dysfunction	9	(1)
Lipid Abnormalities and Cholinergic Failure	10	(1)
Neuritic Abnormalities	10	(1)
Cell Cycle	10	(1)
pH Maintenance	11	(1)
Oxidized Proteins in Alzheimer's Disease Plasma	11	(1)
Proteomic Studies on Oxidatively Modified Proteins in Animal Models of Alzheimer's Disease	11	(5)
Cholinergic Dysfunction-Related Animal Model	12	(1)
SAMP8 Mice	13	(1)
Caenorhabditis Elegans	14	(2)
Future of Proteomics in Alzheimer's Disease	16	(11)
Acknowledgments	16	(1)
References	16	(11)
Direct Evaluation of Alzheimer's Disease-Specific Oxidative Stress with Multiphoton Microscopy	27	(16)
Monica Garcia-Alloza
Sarah A. Dodwell
Brian J. Bacskai
Introduction	27	(1)
Mechanisms of Oxidative Stress-related Toxicity in Alzheimer's Disease	28	(2)
Reactive Oxygen Species in Alzheimers's Disease	29	(1)
Transition Metals in Alzheimer's Disease	29	(1)
Natural Antioxidants	30	(1)
Oxidative Stress Markers	31	(1)
Multiphoton Microscopy	31	(12)
Imaging Reactive Oxygen Species using Multiphoton Microscopy	32	(1)
Effect of Antioxidants on Reactive Oxygen Species associated with Senile Plaques using Multiphoton Microscopy	33	(3)
Acknowledgments	36	(1)
References	37	(6)
Ginkgo biloba Extract and Alzheimer's Disease: Is the Neuroprotection Explained Merely by the Antioxidant Action?	43	(16)
Yves Christen
Abstract	43	(1)
Introduction	44	(1)
Why Antioxidants Such as EGb 761 are Important in the Fight against Alzheimer's Disease?	44	(2)
Ginkgo biloba Extracts	46	(1)
Effects of EGb 761 on Human Subjects	47	(1)
Effects on Cognitive Symptoms in Alzheimer's Disease	47	(1)
Effect on Prevention of Alzheimer's Disease	47	(1)
Other Cognitive Effects	48	(1)
EGb 761 as a Free-radical Scavenger	48	(1)
Effects of EGb 761 on Amyloid-β	48	(1)
Effect of EGb 761 on Gene Expression	49	(1)
Which Additional Effects of EGb 761 could be Linked to the Antioxidant Action?	50	(1)
Why Advance a Hypothesis Whereby There is an Action Over and above a Traditional Antioxidant and Neuroprotective Effect?	50	(9)
References	52	(7)
Mitochondrial Nutrients: Reducing Mitochondrial Decay to Delay or Treat Cognitive Dysfunction, Alzheimer's Disease, and Parkinson's Disease	59	(48)
Jiankang Liu
Bruce N. Ames
Abstract	60	(1)
Introduction	61	(1)
Mitochondrial Decay with Age	61	(1)
The Km concept and metabolism	62	(1)
Possible underlying mechanisms for altered enzyme Km	63	(3)
Protein Oxidation and Adduction by Aldehydes	63	(1)
Protein Nitration and Chlorination	64	(1)
Protein Glycation and Cross-Linking	64	(1)
Protein Degradation/Turnover	64	(1)
Aging-Associated Protein/Enzyme Oxidation	65	(1)
Mt-nutrients and mitochondrial decay	66	(4)
Mt-nutrient deficiency and cognitive dysfunction	70	(8)
Iron Deficiency	71	(3)
Zinc Deficiency	74	(1)
Copper Deficiency	74	(1)
Pantothenic Acid Deficiency	74	(1)
Vitamin B6 Deficiency	75	(1)
Biotin Deficiency	75	(1)
Thiamine Deficiency	75	(1)
Riboflavin Deficiency	76	(1)
Niacin Deficiency	76	(1)
Folate Deficiency	76	(1)
Docosahexaenoic Acid and Eicosapentaenoic Acid (EPA) Deficiency	76	(1)
Choline Deficiency	77	(1)
Acetyl-Carnitine, R-α-Lipoic Acid, Coenzyme Q10, and Creatine Decline	78	(1)
Mt-nutrient Supplementation for the prevention and amelioration of AD and PD	78	(9)
Mitochondrial Decay Due to Oxidative Damage Is a Key Contributor to Aging and Age-Associated Neurodegenerative Diseases, AD and PD	78	(2)
Thiamine Supplementation	80	(1)
Riboflavin Supplementation	81	(1)
Niacin/NADH Supplementation	81	(1)
Folic Acid, B6, and B12 Supplementation	82	(1)
Docosahexaenoic Acid Supplementation	82	(1)
Choline Supplementation	83	(1)
Acetyl-L-Carnitine/L-Carnitine Supplementation	83	(1)
α-Lipoic Acid/Dihydrolipoic Acid Supplementation	84	(2)
Coenzyme Q10 Supplementation	86	(1)
Creatine Supplementation	86	(1)
Effectiveness of combinations of mt-nutrient supplementation on AD and PD prevention and treatment	87	(2)
Conclusions and Perspectives	89	(18)
Acknowledgments	89	(1)
References	90	(17)
Reactive Oxygen and Nitrogen Species: Weapons of Neuronal Destruction	107	(14)
Joseph R. Mazzulli
Summer Lind
Harry Ischiropoulos
Introduction	107	(1)
Acute Neural Injury	108	(1)
Chronic Neurodegenerative Diseases	109	(4)
Alzheimer's Disease	109	(1)
Parkinson's Disease	110	(3)
Concluding Remarks	113	(8)
References	113	(8)
Amyloid-β and τ in Alzheimer's Disease: What is the Neuropathology Trying to Tell Us?	121	(10)
Rudy J. Castellani
Akihiko Nunomura
Hyoung-gon Lee
Xiongwei Zhu
George Perry
Mark A. Smith
Abstract	121	(1)
Introduction	122	(1)
Amyloid-β	122	(2)
Tau	124	(1)
Summary	125	(6)
Acknowledgments	125	(1)
References	126	(5)
Antioxidant Therapies in the Prevention and Treatment of Alzheimer Disease	131	(16)
Paula I. Moreira
Xiongwei Zhu
Akihiko Nunomura
Mark A. Smith
George Perry
Abstract	132	(1)
Introduction	132	(1)
Oxidative Stress	132	(1)
Mitochondria: Source And Target of Oxidative Stress	133	(2)
Antioxidant Therapies	135	(1)
Metabolic Antioxidants	135	(2)
Direct Antioxidants	137	(2)
Indirect Antioxidants	139	(2)
Conclusion	141	(6)
Acknowledgments	141	(1)
References	141	(6)
F2-Isoprostanes as Biomarkers of Late Onset Alzheimer's Disease	147	(12)
Thomas J. Montine
Joseph F. Quinn
Jeffrey A. Kaye
Jason D. Morrow
Alzheimer's Syndrome, Disease, and Dementia	147	(2)
Free Radical-Mediated Damage in Alzheimer's Disease	149	(1)
Assays for F2-IsoPs	149	(1)
F2-IsoPs in the Brain	150	(1)
F2-IsoPs in Ventricular Cerebrospinal Fluid	151	(1)
F2-IsoPs in Lumbar Cerebrospinal Fluid	151	(1)
F2-IsoPs in Plasma and Urine	152	(1)
Summary	153	(6)
Acknowledgments	154	(1)
References	154	(5)
Aspirin and Alzheimer's Disease Protection	159	(22)
Sven E. Nilsson
Stig Berg
Effects of Salicylic Compounds in Plants	159	(1)
Aspirin and the Modern Successors	160	(2)
Side Effects and Risks of Aspirin	162	(1)
Aspirin and Non-aspirin NSAIDS in Modern Pharmacotherapy	163	(1)
Cardiovascular Diseases	163	(1)
Diabetes	163	(1)
Malignancy	164	(1)
Cognitive Decline and Alzheimer's Disease	164	(3)
Circulation	164	(1)
Oxidative Stress	165	(1)
Inflammation	165	(1)
Brain Insulin	166	(1)
Amyloid Deposits	166	(1)
Glutamate Excitoxicity	167	(1)
Clinical Trials	167	(1)
The Octo-Twin Study	168	(1)
Results	169	(5)
Conclusion	174	(7)
References	174	(7)
The Disposition of Lipid-Derived Carbonyls in Alzheimer's Disease	181	(18)
Matthew J. Picklo, Sr.
Introduction	181	(1)
Formation of Lipid-Derived Carbonyls	182	(2)
α, β-unsaturated Aldehydes	182	(1)
γ-keto Aldehyde Prostanoids	183	(1)
Lipid-Derived Carbonyls and AD	184	(1)
Mechanisms of Detoxification	185	(4)
Phase I Metabolism	186	(1)
Reductive Enzymes	186	(1)
Oxidative Enzymes	186	(1)
Phase II Metabolism	187	(2)
Potential Therapeutic Avenues	189	(10)
Acknowledgments	190	(1)
References	190	(9)
Methionine Sulfoxide Reductase System: Possible Roles in Protection against Neurodegenerative Diseases	199	(14)
Jackob Moskovitz
Ashley I. Bush
Abstract	199	(1)
Introduction	200	(1)
Protein Aggregation	201	(1)
Methionine Oxidation and α-Synuclein	202	(2)
Soluble Aβ Levels are Closely Linked to Alzheimer's Disease Pathogenesis	204	(1)
Methionine Oxidation and Amyloid-β	205	(1)
Methionine Oxidation and Prion	206	(1)
Conclusion	207	(6)
References	207	(6)
Nutritional Antioxidant Enrichment and Improved Cognitive Function in Canines	213	(12)
Elizabeth Head
Carl W. Cotman
Introduction	213	(2)
The Canine Model of Human Aging	215	(1)
Age-dependent Cognitive Decline in Canines	215	(1)
Neuropathology in Aged Canines	215	(1)
Treatment With an Antioxidant-Enriched Diet Improves Cognition in Aged Canines	216	(1)
Summary	217	(8)
Acknowledgments	218	(1)
References	218	(7)
Green Tea and Resveratrol as Protective Agents against Neurotoxins	225	(10)
Stephane Bastianetto
Han Ying-Shan
Quirion Remi
Abstract	225	(1)
Introduction	226	(1)
In Vitro Neuroprotective Effects	227	(1)
Resveratrol	227	(1)
Epigallocatechin Gallate	228	(1)
In Vivo Neuroprotective Effects	228	(3)
Resveratrol	228	(2)
Epigallocatechin Gallate	230	(1)
Conclusion	231	(4)
Acknowledgments	232	(1)
References	232	(3)
Oxidative Stress and AβPP Processing	235	(12)
Tabaton Massimo
Tamagno Elena
Introduction	235	(2)
Neurodegeneration and AD	237	(1)
Oxidative Stress and AD	238	(1)
Oxidative Stress and Aβ Overproduction: A Toxic Loop	238	(1)
Hypothetical Sequence of the Pathogenetic Steps of AD	239	(2)
Conclusions	241	(6)
References	243	(4)
Apple Phenolics and Alzheimer's Disease	247	(18)
Ho Jin Heo
Dae-Ok Kim
Chang Yong Lee
Alzheimer's Disease and Amyloid β Protein	247	(1)
Production of Oxidative Stress in Alzheimer's Disease	248	(2)
Aβ and Oxidative Stress	248	(1)
Naturally Occurring Oxidative Stress	249	(1)
High Fragility of Brain on Oxidative Stress	250	(1)
Phytochemicals	250	(2)
Health Benefits	250	(1)
Action of Antioxidants in Alzheimer's Disease	251	(1)
Apple Phenolics	252	(5)
Composition and Antioxidant Capacity in Apple	252	(1)
The Action of Quercetin	253	(4)
Conclusion	257	(8)
References	258	(7)
Effects of Nicotine in Models of Alzheimer's Disease	265	(12)
Baolu Zhao
Abstract	265	(1)
Antioxidant Actions of Nicotine and the Scavenging Effect of Nicotine on Oxygen Free Radicals	266	(1)
Nicotine Inhibits β-Amyloidosis	267	(1)
Nicotine Breaks Down Preformed Alzheimer's Amyloid β Fibrils	268	(1)
Nicotine Protects Hippocampal Neuronal Cells against Aβ-Induced Apoptosis	269	(2)
Chronic Nicotine Treatment Reduces β-Amyloidosis in the Brain of a Mouse Model with Alzheimer's Disease	271	(1)
Conclusion	272	(5)
References	272	(5)
The Essentiality of Iron Chelation in Neuroprotection: A Potential Role of Green Tea Catechins	277	(24)
Silvia A. Mandel
Tamar Amit
Hailin Zheng
Orly Weinreb
Moussa B.H. Youdim
Abstract	277	(1)
Introduction	278	(2)
Neuroprotective Activity of Tea Catechins via Chelation of Divalent Metals	280	(11)
Neuroprotective Effects In Vivo	280	(1)
Neuroprotective Effects In Vitro	281	(1)
Tea Catechins as Brain-Permeable, Nontoxic Iron Chelators to ``Iron Out'' Iron from the Brain	282	(5)
Effect of Tea Catechins on Iron and Hypoxia-Regulated Genes	287	(2)
Effects of Tea Catechins on Cell Signaling Pathways	289	(2)
Conclusions	291	(10)
References	291	(10)
Ginkgo biloba Extract EGb 761 Extends Life Span and Attenuates H2O2 Levels in a Caenorhabditis elegans Model of Alzheimer's Disease	301	(26)
Julie V. Smith
Yuan Luo
Introduction	302	(1)
Reactive Oxygen Species, Aging, and Alzheimer's Disease	303	(2)
Supplemental Antioxidant Therapies	304	(1)
Vitamin E	304	(1)
Vitamin C	305	(1)
Ginkgo biloba Extract	305	(8)
Standardized Ginkgo biloba Extract - EGb 761	305	(1)
Composition of the Extract EGb 761	305	(1)
Identification of Principal Active Compounds or Classes of Compounds Gives Mechanistic Clues to the Action of EGb 761	306	(3)
Clinical use of the Extract EGb 761	309	(1)
The Natural Antioxidant Properties of Ginkgo biloba	310	(1)
Neuroprotective Effects of EGb 761	311	(1)
Antiapoptotic and Antioxidative Properties of EGb 761	311	(1)
Major Biochemical/Pharmacological Activities of EGb 761	312	(1)
Transcriptional Effects of EGb 761	312	(1)
Caenorhabditis elegans, a Valid Model Organism for Pharmacological Evaluation of EGb 761 Protection	313	(4)
The Alzheimer's Disease-Associated Transgenic Caenorhabditis elegans Mutant	313	(1)
Analysis of Reactive Oxygen Species Levels in Caenorhabditis elegans	314	(1)
Alzheimer's Disease-Associated Mutant Models Exhibit Higher Reactive Oxygen Species Levels	314	(2)
Alzheimer's Disease-Associated Caenorhabditis elegans Mutants Exhibit Acceleration of Age-Related Reactive Oxygen Species Production	316	(1)
EGb 761 Components Show Protective Effects in Alzheimer's Models	317	(1)
Kaempferol and Quercetin Attenuate Reactive Oxygen Species Levels In Vitro and In Vivo	317	(1)
Advancement in Recent Methodology for Reactive Oxygen Species Detection	317	(1)
Ginkgo biloba Extract EGb 761 Imparts Stress Resistance and Longevity	318	(1)
Oxidative Stress Resistance in Caenorhabditis elegans Fed with EGb 761	318	(1)
Enhanced Life Span in Caenorhabditis elegans Treated with EGb 761	318	(1)
Summary	319	(8)
References	320	(7)
Cysteine Proteases as β-Secretases for Aβ Production in the Major Regulated Secretory Pathway of Neurons: Implications for Therapeutic Strategies in Alzheimer's Disease	327	(16)
Vivian Hook
Thomas Toneff
Gregory Hook
Terry Reisine
Introduction	328	(1)
β-Amyloid is a Major Factor Involved in Development of Alzheimer's Disease	329	(1)
β-Amyloid Peptide is Generated by Proteolytic Processing of the Amyloid Precursor Protein	329	(1)
β-Amyloid Production and Secretion in the Major Regulated Secretory Pathway of Neurons	330	(1)
Regulated Cosecretion of β-Amyloid with Neurotransmitters from Neuronal Chromaffin Cells in Primary Culture	330	(2)
Chromaffin Vesicles as Regulated Secretory Vesicles for Identification of β-Secretase	332	(1)
Cysteine Proteases for β-Secretase Activity in the Regulated Secretory Pathway of Neurons	333	(3)
Kinetic Studies of the Cysteine β-Secretases Demonstrate their Preference for Cleavage of the Wild-Type β-Secretase Site, Rather than the Swedish Mutant β-Secretase Site	336	(1)
BACE 1 in the Minor Constitutive Secretory Pathway for Basal Secretion of β-Amyloid	337	(2)
Unifying Hypothesis for Distinct Proteases in the Regulated Compared to the Constitutive Secretory Pathways for β-Amyloid Production and Secretion: Strategies for Drug Inhibition of β-Secretase to Treat Alzheimer's Disease	339	(4)
Acknowledgments	339	(1)
References	340	(3)
The Molecular Mechanism of the Neuroprotective Action of Antioxidants Compared with the Anti-Parkinson Drug, Rasagiline	343	(22)
Orly Weinreb
Tamar Amit
Silvia A. Mandel
Moussa B.H. Youdim
Abstract	344	(1)
Introduction	344	(1)
Studies of Neuroprotective Properties in Models of Parkinson's Disease	345	(3)
Antioxidant Agents	345	(2)
Rasagiline	347	(1)
Neuroprotective Studies in Models of Alzheimer's Disease	348	(1)
Antioxidant Agents	348	(1)
Rasagiline	348	(1)
The Mechanisms Underlying Antioxidant-Attenuated Cell Death	349	(3)
Modulation of Cell Signaling Pathways	349	(2)
Effect of Antioxidants on Cell Survival/Death Gene Expression	351	(1)
Mechanism of Action of Rasagiline	352	(3)
Conclusions and Perspectives for the Future	355	(10)
Acknowledgments	355	(1)
References	356	(9)
Temporal Primacy of Oxidative Stress in the Pathological Cascade of Alzheimer Disease	365	(8)
Akihiko Nunomura
Kazuki Tabata
Shigeru Chiba
Mark A. Smith
George Perry
Abstract	365	(1)
Introduction	366	(1)
Genes in Autosomal-Dominant Familial Alzheimer Disease and Oxidative Stress	366	(1)
Risk Factors for Alzheimer Disease and Oxidative Stress	366	(3)
Temporal Primacy of Oxidative Stress in the Pathological Cascade of Alzheimer Disease	369	(1)
Conclusion	369	(4)
References	369	(4)
Age-Related Neuronal and Behavioral Deficits are Improved by Polyphenol-Rich Blueberry Supplementation	373	(22)
Francis C. Lau
Barbara Shukitt-Hale
James A. Joseph
Introduction	373	(1)
Oxidative Stress	374	(3)
Reactive Oxygen Species and Reactive Nitrogen Species	374	(1)
Oxidant--Antioxidant Balance	375	(1)
Age-Related Increase in Oxidative Stress	375	(1)
Inflammation	376	(1)
Neuronal and Behavioral Changes in Aging	377	(1)
Neuronal Changes	377	(1)
Behavioral Deficits	377	(1)
Neuroprotective Effects of Blueberries	378	(4)
Conclusions	382	(13)
References	383	(12)
Amyloid-β Peptide, a Therapeutic Target for Alzheimer's Disease?	395	(14)
Yuan Luo
Peter Butko
Abstract	395	(1)
Introduction	396	(1)
The Amyloid β Cascade Hypothesis of Alzheimer's Disease	396	(1)
Regulating Amyloid β Species In Vitro	397	(2)
Supramolecular Assemblies of Amyloid β	397	(1)
Inhibition of Amyloid β Oligomerization	398	(1)
Modulating Amyloid β Species In Vivo	399	(3)
Animal Models of Alzheimer's Disease	399	(1)
Conventional Pharmacology Targeting Amyloid β Species	400	(1)
Reverse Pharmacology Supporting Amyloid β as a Target	400	(2)
Summary	402	(7)
Acknowledgments	402	(1)
References	403	(6)
Nutrition, Brain Aging and Alzheimer's Disease	409	(34)
Yafei Zhang
Rena Li
Abstract	410	(1)
Introduction	410	(1)
Nutrition and Brain Aging	411	(11)
Caloric Restriction	411	(2)
Essential Nutrients	413	(1)
Fatty Acids	413	(1)
Vitamins	414	(2)
Amino Acids	416	(2)
Minerals	418	(1)
Nonessential Nutrients	419	(1)
Phosphatidylserine	419	(1)
Phytoestrogens	419	(1)
Antioxidants	420	(2)
Nutrition and Alzheimer's Disease	422	(7)
Caloric Restriction	422	(1)
Human Studies	422	(1)
Animal Studies	423	(1)
Fatty Acids	423	(1)
Human Studies	423	(1)
Animal Studies	424	(1)
Vitamins and Homocystiene	424	(1)
Human Studies	424	(2)
Animal Studies	426	(1)
Minerals	426	(1)
Human Studies	426	(1)
Animal Studies	427	(1)
Phosphatidylserine	427	(1)
Human Studies	427	(1)
Animal Studies	428	(1)
Phytoestrogen	428	(1)
Human Studies	428	(1)
Animal Studies	429	(1)
Recommendations	429	(1)
Conclusion	430	(13)
References	431	(12)
Interaction between Dietary and Genetic Deficiencies in the Modulation of Homocysteine Elimination	443	(14)
Flaubert Tchantchou
Thomas B. Shea
Introduction	443	(1)
The Transmethylation Pathway --- Folate Metabolism and Homocysteine Elimination	444	(4)
The Transsulfuration Pathway --- Homocysteine Elimination and Glutathione Metabolism	448	(9)
References	451	(6)
Nutriproteomics Approach to Understanding Dementia-Relevant Brain Protein Changes in Response to Grape Seed Extract, a Dietary Antioxidant	457	(24)
Helen Kim
Shannon Eliuk
Jessy Deshane
Stephen Barnes
Sreelatha Meleth
Abstract	459	(1)
Introduction	459	(2)
Application of Proteomics Technologies in the Identification of Targets of Antioxidants in Normal and Diseased Mammalian Brain	461	(3)
Normal Young Adult Rat Brain	461	(1)
Transgenic Model of Dementia, the Tg2576 Mouse	461	(1)
Rodent Brain Tissue Preparation for Two-Dimensional Electrophoresis	461	(1)
Derivatization of Protein Carbonyls with 2,4-Dinitrophenylhydrazine	462	(1)
Protein Extraction and Concentration with Methanol-Chloroform	462	(1)
Two-Dimensional Gel Electrophoresis	462	(1)
Western-Blot Analysis	463	(1)
Image Analysis	463	(1)
Mass Spectrometry Methods to Identify Proteins Following Image Analysis	463	(1)
Peptide Mass Fingerprint Analysis Using Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry	463	(1)
Liquid Chromatography--Tandem--Mass Spectroscopy	464	(1)
Statistical Analysis	464	(1)
Findings from Proteomics Investigations of Actions of Grape Seed Extract	464	(3)
Proteins that Discriminated 100% between Grape Seed Extract and Control Dietary Groups	464	(1)
Validation of Putative Protein Identifications Generated by Peptide Mass Fingerprint Analysis	465	(1)
Western-Blot Analysis for Protein Oxidations Affected by Grape Seed Extract in the Tg2576 Mouse Brain	465	(2)
Initial Conclusions	467	(6)
Proteins in Normal Young Adult Mammalian Brain are Affected by Grape Seed Extract	467	(2)
Attenuation of Protein Oxidations in Tg2576 Brains by Grape Seed Extract	469	(1)
Challenges for the Future in Analysis of Neurodegeneration-Relevant Protein Oxidations	470	(1)
Rigorous Identification of DNP-Modified Proteins	470	(1)
Identifying the DNP-Modified Peptides and the Modified Amino Acid Residues	471	(1)
How Do We Know if the Specific Protein Oxidations are Functionally Related to the Disease?	471	(1)
Role of Proteomics in Nutrition-Related Research	471	(1)
2D Gel Patterns are Informative even without Protein Identification	471	(1)
Rationale for Analysis of Intact vs. Proteolytically Cleaved Proteins	472	(1)
Identification of Intact Proteins Affected by Potentially Pathologic Modifications is Essential for Understanding the Disease Process	472	(1)
Summary	473	(8)
Timing of the Baby Boomers Coincident with Emerging Technologies Enables Concerted Efforts in Analysis of Chronic Diseases	473	(1)
Elements of Productive Proteomics	473	(2)
Proteomics Identification of Effects/Targets of Dietary Antioxidants in Chronic Conditions Such as Neurodegeneration: Value-Added Research	475	(1)
Acknowledgments	476	(1)
References	477	(4)
Index	481