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Biometals in Neurodegenerative Diseases - 1st Edition - ISBN: 9780128045626, 9780128045633

Biometals in Neurodegenerative Diseases

1st Edition

Mechanisms and Therapeutics

Editors: Anthony White Michael Aschner Lucio Costa Ashley Bush
Hardcover ISBN: 9780128045626
eBook ISBN: 9780128045633
Imprint: Academic Press
Published Date: 28th April 2017
Page Count: 462
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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


Academic researchers, clinicians, and advanced graduate students studying or treating patients in neurodegeneration, neurochemistry, neurology, and neurotoxicology

Table of Contents

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-β Peptide: Coordination, Aggregation, and Reactive Oxygen Species Production
Melisa del Barrio, Valentina Borghesani, Christelle Hureau and Peter Faller

  • Abstract
  • Introduction
  • Structure of the Metal-Aβ Complexes
  • Affinity of Metals to Aβ
  • 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


No. of pages:
© Academic Press 2017
28th April 2017
Academic Press
Hardcover ISBN:
eBook ISBN:

About the Editors

Anthony White

Anthony White

Associate Professor Anthony White is a Group Leader at the QIMR Berghofer Medical Research Institute in Queensland, Australia. He is also an Honorary Principal Research Fellow at The University of Melbourne, and an Adjunct Professor in Translational Neuroscience at A.I. Virtanen Institute, University of Eastern Finland. He investigates the cellular pathology of neurodegenerative diseases, and has a strong focus on the role of biometals in neurodegenerative processes, and as novel targets for neurotherapeutics. His research has led to the development of first-in-class metal-drugs as a potential new therapeutic approach to treat motor neuron, Parkinson’s and Alzheimer’s diseases through the targeting of complementary biometal pathways in these disorders. He has published over 120 original research papers, reviews and book chapters, is Associate Editor for Neurochemistry International and co-founded a start-up biotech company (Procypra Therapeutics) that has delivered a novel copper-based metal-drug to clinical trials for motor neuron disease. He has been awarded prestigious research fellowships including National Health and Medical Research Council (NHMRC) R.D Wright Fellowship, and Senior Research Fellowship, and Australian Research Council (ARC) Future Fellowship. His research has contributed to the understanding of copper interactions with the amyloid precursor protein (APP) and amyloid beta peptide in Alzheimer’s disease, and more recently, the key role of copper in cell signaling and neuroinflammatory processes.

Affiliations and Expertise

University of Melbourne, Victoria, Australia

Michael Aschner

Michael Aschner

Dr. Aschner serves as the Harold and Muriel Block Chair in Molecular Pharmacology at Albert Einstein College of Medicine. He served on numerous toxicology panels (Institute of Medicine, US Environmental Protection Agency, Center for Disease Control), and is a member of the Neurotoxicology and Alcohol study section (NIH). Research in our lab focuses on the following topics: (1) Modulation of C. elegans genes (aat, skn-1, daf-16) that are homologous to mammalian regulators of MeHg uptake and cellular resistance will modify dopaminergic neurodegeneration in response to MeHg exposure. (2) Under conditions of MeHg-induced oxidative stress, Nrf2 (a master regulator of antioxidant responses) coordinates the upregulation of cytoprotective genes that combat MeHg-induced oxidative injury, and that genetic and biochemical changes that negatively impact upon Nrf2 function increase MeHg’s neurotoxicity. (3) PARK2, a strong PD genetic risk factor, alters neuronal vulnerability to modifiers of cellular Mn status, particularly at the level of mitochondrial dysfunction and oxidative stress. Our studies are designed to (1) shed novel mechanistic insight into metal-induced neurodegeneration; (2) identify targets for genetic or pharmacologic modulation of neurodegenerative disorders; (3) increase knowledge of the pathway involved in oxidative stress; (4) develop improved research models for human disease using knowledge of environmental sciences.

Affiliations and Expertise

Professor, Department of Molecular Pharmacology, Albert Einstein College of Medicine, NY, USA

Lucio Costa

Lucio Costa

Dr. Lucio G. Costa is Professor of Toxicology at the University of Washington in Seattle, and of Pharmacology/Toxicology at the University of Parma Medical School. He received a doctorate in Pharmacology from the University of Milano in 1977, and was a postdoctoral fellow at the University of Texas at Houston. He is a member of several national and international professional organizations, a Fellow of the Academy of Toxicological Sciences, and a European Certified Toxicologist. He received various award for his scientific accomplishments, including the Achievement Award from the Society of Toxicology. He serves in various editorial capacities for several toxicology journals, and is an active manuscript and grant reviewer. Dr. Costa has been the member of dozens of panels and committees at the national and international level dealing with toxicology and risk assessment issues. He has chaired and/or organized symposia at scientific meetings in the United States and internationally. He has been teaching classes in the area of toxicology, neurotoxicology and pharmacology to graduate and medical students for 30 years. He keeps an active research program in the area of neurotoxicology.

Affiliations and Expertise

Professor of Toxicology, University of Washington, Seattle, WA, USA

Ashley Bush

Ashley Bush

Dr. Bush is a Professor at the Florey Institute of Neuroscience and Mental Health in Parkville, Victoria, Australia. He is also the Director of the Oxidation Biology Unit. Dr. Bush’s laboratory looks at how key proteins interact inappropriately with metals in the brain to cause oxidative stress in diseases including Alzheimer’s and Parkinson’s. He is actively working to develop disease-modifying drugs for Alzheimer’s and Parkinson's diseases, as well as blood tests for the disorders.

Affiliations and Expertise

Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia

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