Note: Cover -- Title page -- Copyright page -- Contents -- Contributors -- Preface -- Chapter 1 - Biometals and Alzheimer's Disease -- Introduction -- The Role of Copper in AD -- The Role of Zinc in AD -- The Role of Iron in AD -- Therapeutic Targeting of Biometals in AD -- Conclusions -- References -- Chapter 2 - Copper in Alzheimer's Disease -- Introduction -- The Physiology of Copper -- Copper Absorption and Distribution -- Copper in the Liver -- Copper's Path From General Circulation to the Brain -- The Key Role of Ceruloplasmin -- Copper Toxicity -- The Role of Copper in Alzheimer's Disease -- Genetics of Copper and AD -- The AD Copper Subtype -- Conclusions -- References -- Chapter 3 - The Role of Selenium in Neurodegenerative Diseases -- Introduction -- Selenoproteins and the Selenoproteome -- Selenium and Alzheimer's Disease -- Parkinson's Disease -- Other Neurodegenerative Diseases -- Conclusions -- References -- Chapter 4 - Does HFE Genotype Impact Macrophage Phenotype in Disease Process and Therapeutic Response? -- Iron -- Hemochromatosis -- Discovery -- Types -- HFE -- Structure -- Function -- Polymorphisms -- Macrophages -- Macrophage and Iron Metabolism -- Macrophage Polarization -- Macrophages and HFE -- HFE and Neurodegenerative Diseases -- Alzheimer's Disease -- Amyotrophic Lateral Sclerosis -- Parkinson's Disease -- HFE and Cancer -- HFE Animal Models -- Conclusions -- References -- Chapter 5 - Chemical Elements and Oxidative Status in Neuroinflammation -- Introduction -- Metal-Induced Neurotoxicity and Multiple Sclerosis -- Metals and Oxidative Status in Multiple Sclerosis -- Metals and Oxidative Status in Clinically Isolated Syndromes -- Conclusions -- References -- Chapter 6 - Metals and Neuroinflammation -- Introduction -- Mechanisms by Which Metal Elements Can Incite Immune Activity -- Metals as Haptens. , Metal Elements with Valence Instability -- Copper (Cu) -- Iron (Fe) -- Manganese -- Metals Attaching to Sulfhydryl Residues -- Lead (Pb) -- Mercury (Hg) -- Metals Associated with Particulate and Colloidal Materials -- Aluminum (Al) -- Titanium, Silver and Gold (Ti, Ag, Au) -- Metals Which Lead to Oxidative Stress and Inflammation by Means that are not yet Understood -- The Relation Between Reactive Oxygen and Nitrogen Species and Inflammation -- Conclusions -- References -- Chapter 7 - Metals and Prions: Twenty Years of Mining the Awe -- Prion Diseases -- Prion Protein -- Prion Protein Function -- Copper and PrP -- Zinc and PrP -- Iron and PrP -- Manganese and PrP -- Metals in Prion Disease -- Chelation Therapy and Prion Disease -- Conclusions -- References -- Chapter 8 - Manganese and Neurodegeneration -- Background -- Mn Essentiality and Metabolic Functions -- Mn Biokinetics and Homeostatic Control -- Routes and Sources of Mn Exposure -- Absorption of Airborne Mn -- Parenteral Exposure to Mn -- Oral Absorption of Mn From Food and Water -- Mn Biodistribution and Elimination -- Biokinetics of Mn in Brain -- Mn Transport Into Brain -- Regional Delivery of Mn in the Brain -- Mn Elimination From Brain Compartment -- Subcellular Distribution of Mn in Brain -- Homeostatic Control of Mn -- Influence of Age and Gender on Mn Metabolism -- Influence of Age on Mn Metabolism -- Influence of Gender on Mn Metabolism -- Toxicological Evaluation Mn Levels in Nutrition -- Neurotoxicology of Mn -- Deficient Exposure -- Mn Overexposure -- Clinical Features -- Modulating Factors of Mn Induced Neurotoxicity -- Mn dosage -- Duration of Mn supplementation -- Co-morbidities associated with Mn exposure -- Neuropathological Features -- Selected Mechanisms of Mn-Induced Neurotoxicity -- Alterations of Glutamatergic, GABAergic and dopaminergic (DAergic) systems. , Impaired Energy Metabolism -- Oxidative stress -- Biomonitoring of Mn in Patients Undergoing PN -- Biomarkers of Exposure, Effect, and Susceptibility -- Classical Approach of Mn Biomonitoring in PN Patients: Biomarkers of Exposure -- Mn Concentration in Body Fluids -- Magnetic Resonance Imaging (MRI) -- Alternative Approaches: Subclinical Biomarkers Predictive of Mn-Induced Neurotoxicity -- Neurobehavioral Tests -- Neuroimaging Biomarker: 1H Proton Magnetic Resonance Spectroscopy -- Hematologic and Urinary Biomarkers Related to Catecholaminergic System -- Conclusions -- Acknowledgment -- References -- Chapter 9 - Zinc in Autism -- Introduction -- Zinc signaling in autism -- Zinc and Inflammatory Processes in Autism -- Zinc and Synaptic Dysfunction in Autism-Molecular Pathways -- Therapeutic Strategies in Autism Based on Biometals -- Conclusions -- References -- Chapter 10 - Metals and Motor Neuron Disease -- List of Abbreviations -- Introduction -- Metal Exposure -- Metals in ALS Cerebrospinal Fluid -- Metals in ALS -- Protection by Metallothionein -- Metal Distribution in ALS -- Metal Related ALS Clusters -- ALS and Occupational Exposures to Metals -- Conjugal ALS -- Genetic Aspects -- Concluding Remarks -- References -- Chapter 11 - Metals and Lysosomal Storage Disorders -- Introduction -- Common Pathological Features of Lysosomal Storage Disorders -- Endosomal-Autophagic-Lysosomal System -- Lysosomal Dysfunction in LSDs -- Neuroinflammation -- Calcium Homeostasis, ER Stress, and Oxidative Stress in LSDs -- Description of Most Common Neurodegenerative LSDs Associated with Biometal Imbalance -- Gaucher Disease Type II and III -- Niemann Pick Type C1 -- Neuronal Ceroid Lipofuscinosis or Batten Disease -- Function and Regulation of Biometals -- Biometals in CNS -- Biometals in Lysosomes -- Loss of Biometal Homeostasis is Connected to Disease. , Role of Biometals and Biometal Binding Proteins in LSDs -- LSDs and Iron Homeostasis -- LSDs and Copper Homeostasis -- LSDs and Zinc Homeostasis -- Targeting Metals to Treat Disease -- References -- Chapter 12 - Developmental Exposure to Metals and its Contribution to Age-Related Neurodegeneration -- Introduction -- Developmental Exposure to Toxicants and Late Effects -- Developmental Lead Exposure and Alzheimer's Disease -- Developmental Arsenic Exposure and Alzheimer's Disease -- Conclusions and Future Perspectives -- Acknowledgment -- References -- Chapter 13 - Metal Biology Associated with Huntington's Disease -- Introduction -- The Epidemiology of HD -- The Symptoms of HD -- The Neuropathology of HD -- Biological Function of Wild-type and Pathogenic HTT Proteins -- Autophagy and Metals in Huntington's Disease -- Exosomes and Metal in Huntington's Disease -- Environmental Factors Impacting HD -- Metals in HD -- Iron in HD -- Copper in HD -- Calcium in HD -- Manganese in HD -- Manganese Deposition: Brain Regions, Cell Types, and Cellular Organelles -- Regional Deposition -- Cell-Type Deposition -- Subcellular Deposition -- Manganese Dyshomeostasis in HD -- Mn-Dependent and Mn-Utilizing Enzymes -- GS-Glutamine Synthetase -- SOD2-Mn-Dependent Superoxide Dismutase -- ARG1 and ARG2-Arginase -- ATM-Ataxia Telangiectasia Mutated -- MRE-11-Meiotic Recombination 11, and FAN1-Fanconi's Associated Nuclease 1 -- Intracellular pH and Metal Biology in HD -- Metal-Related Clinical Interventions in HD -- Conclusions and Future Directions -- References -- Chapter 14 - Metal-Binding to Amyloid-β Peptide: Coordination, Aggregation, and Reactive Oxygen Species Production -- Introduction -- Interest in Chemistry of Metal-Amyloid-β Complexes -- Structure of the Metal-Aβ Complexes -- Coordination of Metal Ions Cu, Zn, and Fe to Soluble, Monomeric Amyloid-β. , Cu(II)-β-Amyloid -- Cu(I)-β-Amyloid -- Zn(II)-β-Amyloid -- Fe(II)-β-Amyloid -- Cu(II) Coordination to Aβ With Disease Relevant Mutations or Other Derivatives -- Coordination of Metal Ions Cu and Zn to Aggregated β-Amyloid -- Cu(II) Coordination to Aggregated Aβ Peptide -- Cu(I) Coordination to Aggregated Aβ Peptide -- Zn(II) Coordination to Aggregated Aβ Peptide -- Affinity of Metals to Aβ -- Affinity of Metal Ions Cu(I/II) and Zn(II) to Soluble, Monomeric Amyloid-β -- Affinity of Metal Ions Cu(I/II) and Zn(II) to Aggregated β-Amyloid -- Cu(II) versus Zn(II) Binding -- Aggregation -- General Consideration for Aβ -- Impact of Metal Ions on Aβ Aggregation -- Reactive Oxygen Species Induced Oxidative Stress -- Reactive Oxygen Species Production by Cu-Aβ Complexes -- Cu-Aβ and ROS Production -- Redox Chemistry of Cu-Aβ Complexes by Cyclic Voltammetry -- Mechanism of ROS Production and the Reactive State of Cu-Aβ Complexes -- The Fenton type reaction -- Dioxygen Reduction -- Efficiency and Biological Relevance of the ROS Production by Cu-Aβ Complexes -- Conclusions -- Acknowledgments -- References -- Chapter 15 - Metals and Mitochondria in Neurodegeneration -- Introduction -- Iron Dyshomeostasis -- Copper Dislocation -- Zinc Deficiency -- Mitochondrial Dysfunction -- Conclusions -- Acknowledgments -- References -- Chapter 16 - Metal Transporters in Neurodegeneration -- Iron Transporters and Neurodegeneration -- Tf-TfR -- DMT1 -- Fpn -- Lf-LfR -- MTf -- Iron Transporters and PD -- Iron Transporters and AD -- Iron and Other Neurodegenerative Disorders -- Zinc Transporters and Neurodegeneration -- ZnT -- ZIP -- MTs -- Zinc Transporters and PD -- Zinc Transporters and AD -- Zinc Transporters and Other Neurodegenerative Diseases -- Copper Transporters and Neurodegeneration -- CTR1 -- The ATPases ATP7A/ATP7B -- Copper Transporters and PD. , Copper Transporters and AD.