Biometals in Neurodegenerative Diseases: Mechanisms and Therapeutics is an authoritative and timely resource bringing together the major findings in the field for ease of access to those working in the field or with an interest in metals and their role in brain function, disease, and as therapeutic targets. Chapters cover metals in Alzheimer’s Disease, Parkinson’s Disease, Motor Neuron Disease, Autism and lysosomal storage disorders.
This book is written for academic researchers, clinicians and advanced graduate students studying or treating patients in neurodegeneration, neurochemistry, neurology and neurotoxicology. The scientific literature in this field is advancing rapidly, with approximately 300 publications per year adding to our knowledge of how biometals contribute to neurodegenerative diseases.
Despite this rapid increase in our understanding of biometals in brain disease, the fields of biomedicine and neuroscience have often overlooked this information. The need to bring the research on biometals in neurodegeneration to the forefront of biomedical research is essential in order to understand neurodegenerative disease processes and develop effective therapeutics.
Key Features
- Authoritative and timely resource bringing together the major findings in the field for those with an interest in metals and their role in the brain function, disease, and as therapeutic targets
- Written for academic researchers, clinicians, and advanced graduate students studying, or treating, patients in neurodegeneration, neurochemistry, neurology and neurotoxicology
- Edited by international leaders in the field who have contributed greatly to the study of metals in neurodegenerative diseases
Chapter 1: Biometals and Alzheimer’s Disease
Alexandra I. Mot and Peter J. Crouch
- Abstract
- 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
Chapter 2: Copper in Alzheimer’s Disease
Rosanna Squitti, Mariacarla Ventriglia, Mariacristina Siotto and Carlo Salustri
- Abstract
- Introduction
- The Physiology of Copper
- Copper Toxicity
- Conclusions
Chapter 3: The Role of Selenium in Neurodegenerative Diseases
Bárbara R. Cardoso, Dominic J. Hare and Ashley I. Bush
- Abstract
- Introduction
- Selenoproteins and the Selenoproteome
- Selenium and Alzheimer’s Disease
- Parkinson’s Disease
- Other Neurodegenerative Diseases
- Conclusions
Chapter 4: Does HFE Genotype Impact Macrophage Phenotype in Disease Process and Therapeutic Response?
Anne M. Nixon and James R. Connor
- Abstract
- Iron
- Hemochromatosis
- HFE
- Macrophages
- HFE Animal Models
- Conclusions
Chapter 5: Chemical Elements and Oxidative Status in Neuroinflammation
Michela Ferraldeschi, Silvia Romano, Maria Chiara Buscarinu, Arianna Fornasiero, Rosella Mechelli, Benedetta Cerasoli, Anna Pino, Sonia Brescianini, Carlo Mattei, Maria Antonia Stazi, Alessandro Alimonti, Marco Salvetti and Giovanni Ristori Sr.
- Abstract
- Introduction
- Metal-Induced Neurotoxicity and Multiple Sclerosis
- Metals and Oxidative Status in Multiple Sclerosis
- Metals and Oxidative Status in Clinically Isolated Syndromes
- Conclusions
Chapter 6: Metals and Neuroinflammation
Stephen C. Bondy
- Abstract
- Introduction
- Mechanisms by Which Metal Elements Can Incite Immune Activity
- The Relation Between Reactive Oxygen and Nitrogen Species and Inflammation
- Conclusions
Chapter 7: Metals and Prions: Twenty Years of Mining the Awe
David R. Brown
- Abstract
- 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
Chapter 8: Manganese and Neurodegeneration
Dinamene Marques dos Santos, Michael Aschner and Ana Paula Marreilha dos Santos
- Abstract
- Background
- Mn Essentiality and Metabolic Functions
- Mn Biokinetics and Homeostatic Control
- Neurotoxicology of Mn
- Biomonitoring of Mn in Patients Undergoing PN
- Conclusions
- Acknowledgment
Chapter 9: Zinc in Autism
Stefanie Grabrucker and Andreas Grabrucker
- Abstract
- Introduction
- Zinc Signaling in Autism
- Therapeutic Strategies in Autism Based on Biometals
- Conclusions
Chapter 10: Metals and Motor Neuron Disease
Per M. Roos
- Abstract
- List of Abbreviations
- Introduction
- Metal Exposure
- Metals in ALS Cerebrospinal Fluid
- Metals in ALS
- Protection by Metallothionein
- Metal Distribution in ALS
- Genetic Aspects
- Concluding Remarks
Chapter 11: Metals and Lysosomal Storage Disorders
H. Konttinen, K. Lejavová, T. Malm and Katja Kanninen
- Abstract
- Introduction
- Common Pathological Features of Lysosomal Storage Disorders
- Description of Most Common Neurodegenerative LSDs Associated with Biometal Imbalance
- Function and Regulation of Biometals
- Role of Biometals and Biometal Binding Proteins in LSDs
- Targeting Metals to Treat Disease
Chapter 12: Developmental Exposure to Metals and its Contribution to Age-Related Neurodegeneration
Lucio G. Costa
- Abstract
- 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
Chapter 13: Metal Biology Associated with Huntington’s Disease
Terry Jo Vetters Bichell, Timothy C. Halbesma, K. Grace Tipps and Aaron Bowman
- Abstract
- 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
- Manganese Dyshomeostasis in HD
- Mn-Dependent and Mn-Utilizing Enzymes
- Intracellular pH and Metal Biology in HD
- Metal-Related Clinical Interventions in HD
- Conclusions and Future Directions
Chapter 14: Metal-Binding to Amyloid-ß Peptide: Coordination, Aggregation, and Reactive Oxygen Species Production
Melisa del Barrio, Valentina Borghesani, Christelle Hureau and Peter Faller
- Abstract
- Introduction
- Structure of the Metal-Aß Complexes
- Affinity of Metals to Aß
- Aggregation
- Reactive Oxygen Species Induced Oxidative Stress
- Conclusions
- Acknowledgments
Chapter 15: Metals and Mitochondria in Neurodegeneration
Germán Plascencia-Villa, Miguel José Yacamán and George Perry
- Abstract
- Introduction
- Iron Dyshomeostasis
- Copper Dislocation
- Zinc Deficiency
- Mitochondrial Dysfunction
- Conclusions
- Acknowledgments
Chapter 16: Metal Transporters in Neurodegeneration
Hong Jiang
- Abstract
- Iron Transporters and Neurodegeneration
- Zinc Transporters and Neurodegeneration
- Copper Transporters and Neurodegeneration
- Manganese Transporters and Neurodegeneration
- Magnesium Transporters and Neurodegeneration
- Aluminum Transporters and Neurodegeneration
- Conclusions
Chapter 17: Metal Imaging in the Brain
David C. Dorman
- Abstract
- Introduction
- Introduction to MRI Physics
- MRI Contrast Agents
- Gadolinium
- Iron
- Copper
- Manganese
Chapter 18: Metalloregulation of Protein Clearance: New Therapeutic Avenues for Neurodegenerative Diseases
A. Ramírez Muñoz, M. A. Greenough, Ashley I. Bush and C. M. Opazo
- Abstract
- Introduction
- Metalloregulation of the Ubiquitin Proteasome System: Implication in Neurodegenerative Diseases
- Metals as Mediators of Autophagy-Lysosomal Response
- Conclusions
- Acknowledgments
Chapter 19: Metals and Autophagy in Neurotoxicity
Peng Su, Michael Aschner, Jingyuan Chen and Wenjing Luo
- Abstract
- Introduction
- Part 1 Metal-Related Neurotoxicity and Neurodegenerative Diseases
- Part 2 Autophagy in Metal Neurotoxicity
- Conclusions
- Acknowledgments
Chapter 20: An Overview of Multifunctional Metal Chelators as Potential Treatments for Neurodegenerative Diseases
Frank W. Lewis and David Tétard
- Abstract
- Introduction
- Parent Metal Chelators
- Multifunctional Metal Chelators
- Conclusions
Chapter 21: Abnormal Function of Metalloproteins Underlies Most Neurodegenerative Diseases
Katja Kanninen and Anthony R. White
- Abstract
- Background
- Biometals
- Abnormal Biometal Levels and Distribution Underlie Most Forms of Neurodegeneration
- Abnormal Metalloprotein Function Underlying Neurodegenerative Diseases
- Neurodegenerative Diseases Caused by Mutation in Metalloproteins
- Neurodegenerative Diseases Associated With Abnormal Metalloprotein Function
- Neurodegenerative Diseases Involving Biometal Changes but Without a Clearly Identified Role for Metalloprotein Abnormities
- Neurodegenerative Diseases Where No Major Role for Biometals or Metalloproteins Has Yet Been Identified
- Conclusions
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- Zigmond, Neurobiology of Brain Disorders, 9780123982704, Dec 2014, 864 pages, $150.00
- Rosenberg, Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease 5e, 1330 pages, Nov 2014, 9780124105294, $225.00
- Seneci, Molecular Targets in Protein Misfolding and Neurodegenerative Disease, 9780128001868, Oct 2014, 314pp, $125.00
- Blum, Adenosine Receptors in Neurodegenerative Diseases, 9780128037249, Mar 2017, 300 pages, $150.00
Academic researchers, clinicians, and advanced graduate students studying or treating patients in neurodegeneration, neurochemistry, neurology, and neurotoxicology
