4. IRONING OUT THE BRAIN
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Roberta J. Ward
Abstract
Our understanding of the broad principles of cellular and systemic iron homeostasis in man are well established with the exception of the brain. Most of the proteins involved in mammalian iron metabolism are present in the brain, although their distribution and precise roles in iron uptake, intracellular metabolism and export are still uncertain, as is the way in which systemic iron is transferred across the blood-brain barrier. We briefly review current concepts concerning the uptake and distribution of iron in the brain, before turning to the ways in which brain iron homeostasis might be regulated. The distribution of iron between different brain regions is then discussed as is the increase in brain iron with normal aging, and the different forms in which iron is present. The increased levels of iron found in specific brain regions and their potential contribution to neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and other polyglutamine expansion diseases, amyotrophic lateral sclerosis, Friedreich’s ataxia, as well as a number of neurodegenerative diseases with iron accumulation, are discussed. The interactions between neuroinflammation and iron are presented, and the chapter concludes with a review of current clinical studies and discussion of the potential and efficacy of iron chelation therapy in the treatment of neurodegenerative diseases.
Abstract
Our understanding of the broad principles of cellular and systemic iron homeostasis in man are well established with the exception of the brain. Most of the proteins involved in mammalian iron metabolism are present in the brain, although their distribution and precise roles in iron uptake, intracellular metabolism and export are still uncertain, as is the way in which systemic iron is transferred across the blood-brain barrier. We briefly review current concepts concerning the uptake and distribution of iron in the brain, before turning to the ways in which brain iron homeostasis might be regulated. The distribution of iron between different brain regions is then discussed as is the increase in brain iron with normal aging, and the different forms in which iron is present. The increased levels of iron found in specific brain regions and their potential contribution to neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and other polyglutamine expansion diseases, amyotrophic lateral sclerosis, Friedreich’s ataxia, as well as a number of neurodegenerative diseases with iron accumulation, are discussed. The interactions between neuroinflammation and iron are presented, and the chapter concludes with a review of current clinical studies and discussion of the potential and efficacy of iron chelation therapy in the treatment of neurodegenerative diseases.
Chapters in this book
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series vii
- Preface to Volume 19 ix
- Contents xiii
- Contributors to Volume 19 xix
- Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
- Contents of Volumes in the Metal Ions in Life Sciences Series xxv
- 1. METALS IN MEDICINE: THE THERAPEUTIC USE OF METAL IONS IN THE CLINIC 1
- 2. SMALL MOLECULES: THE PAST OR THE FUTURE IN DRUG INNOVATION? 17
- 3. IRON CHELATION FOR IRON OVERLOAD IN THALASSEMIA 49
- 4. IRONING OUT THE BRAIN 87
- 5. INFECTIONS ASSOCIATED WITH IRON ADMINISTRATION 123
- 6. IRON OXIDE NANOPARTICLE FORMULATIONS FOR SUPPLEMENTATION 157
- 7. BUILDING A TROJAN HORSE: SIDEROPHORE-DRUG CONJUGATES FOR THE TREATMENT OF INFECTIOUS DISEASES 181
- 8. DEVELOPING VANADIUM AS AN ANTIDIABETIC OR ANTICANCER DRUG: A CLINICAL AND HISTORICAL PERSPECTIVE 203
- 9. CHROMIUM SUPPLEMENTATION IN HUMAN HEALTH, METABOLIC SYNDROME, AND DIABETES 231
- 10. MANGANESE: ITS ROLE IN DISEASE AND HEALTH 253
- 11. COBALT-SCHIFF BASE COMPLEXES: PRECLINICAL RESEARCH AND POTENTIAL THERAPEUTIC USES 267
- 12. COPPER DEPLETION AS A THERAPEUTIC STRATEGY IN CANCER 303
- 13. METAL COMPOUNDS IN THE DEVELOPMENT OF ANTIPARASITIC AGENTS: RATIONAL DESIGN FROM BASIC CHEMISTRY TO THE CLINIC 331
- 14. CHEMICAL AND CLINICAL ASPECTS OF METAL-CONTAINING ANTIDOTES FOR POISONING BY CYANIDE 359
- SUBJECT INDEX 393
Chapters in this book
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series vii
- Preface to Volume 19 ix
- Contents xiii
- Contributors to Volume 19 xix
- Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
- Contents of Volumes in the Metal Ions in Life Sciences Series xxv
- 1. METALS IN MEDICINE: THE THERAPEUTIC USE OF METAL IONS IN THE CLINIC 1
- 2. SMALL MOLECULES: THE PAST OR THE FUTURE IN DRUG INNOVATION? 17
- 3. IRON CHELATION FOR IRON OVERLOAD IN THALASSEMIA 49
- 4. IRONING OUT THE BRAIN 87
- 5. INFECTIONS ASSOCIATED WITH IRON ADMINISTRATION 123
- 6. IRON OXIDE NANOPARTICLE FORMULATIONS FOR SUPPLEMENTATION 157
- 7. BUILDING A TROJAN HORSE: SIDEROPHORE-DRUG CONJUGATES FOR THE TREATMENT OF INFECTIOUS DISEASES 181
- 8. DEVELOPING VANADIUM AS AN ANTIDIABETIC OR ANTICANCER DRUG: A CLINICAL AND HISTORICAL PERSPECTIVE 203
- 9. CHROMIUM SUPPLEMENTATION IN HUMAN HEALTH, METABOLIC SYNDROME, AND DIABETES 231
- 10. MANGANESE: ITS ROLE IN DISEASE AND HEALTH 253
- 11. COBALT-SCHIFF BASE COMPLEXES: PRECLINICAL RESEARCH AND POTENTIAL THERAPEUTIC USES 267
- 12. COPPER DEPLETION AS A THERAPEUTIC STRATEGY IN CANCER 303
- 13. METAL COMPOUNDS IN THE DEVELOPMENT OF ANTIPARASITIC AGENTS: RATIONAL DESIGN FROM BASIC CHEMISTRY TO THE CLINIC 331
- 14. CHEMICAL AND CLINICAL ASPECTS OF METAL-CONTAINING ANTIDOTES FOR POISONING BY CYANIDE 359
- SUBJECT INDEX 393
