Metal Ions And Neurodegenerative Disorders

Numerous studies have established a clear connection between neuronal oxidative stress and several neurodegenerative diseases, with consequential damages to lipids, proteins, nucleic acids, etc. In addition, several modifications indicative of oxidative stress have been described in association with neurons, neurofibrillary tangles and senile plaques in Alzheimer's disease, including advanced glycation end products and free carbonyl oxidation.Oxidative damage and antioxidant responses are now well characterized, but sources of damaging free radicals are yet to be fully understood. Evidences of alteration in metal ions metabolism have been reported in various diseases like Alzheimer's, Wilson, Menkes, Prion, Pick, Huntington disease, epilepsy and other pathological events. Thus, metal ions play a pivotal role in neurodegenerative phenomena.Chelation therapy is still in the early days of its development, but research in this area could lead to new products that could revolutionize treatment. Two international conferences on ?Metals and the Brain: From Neurochemistry to Neurodegeneration? (Padova, Italy, 2000 and Fez, Morocco, 2002) were recently held to discuss the role of metal ions in neurophysiopathology. A third will be held in 2005 in Johannesburg, South Africa.This book follows the same train of thought as those conferences, in order to highlight the unquestionable importance of metal ions in the research on the neurophysiopathology of neurodegenerative diseases. The excellent reputation of the scientists who have contributed to this project ensures the quality of the chapters presented here, and hopefully this will help spur new research initiatives in the field, which is still in its infancy.

About the Series... Metal Ions in Life Sciences links coordination chemistry and biochemistry in their widest sense and thus increases our understanding of the relationship between the chemistry of metals and life processes. The series reflects the interdisciplinary nature of Biological Inorganic Chemistry and coordinates the efforts of scientists in fields like biochemistry, inorganic chemistry, coordination chemistry, molecular and structural biology, enzymology, environmental chemistry, physiology, toxicology, biophysics, pharmacy, and medicine. Consequently, the volumes are an essential source for researchers active in these and related fields as well as teachers preparing courses, e.g., in Bioinorganic Chemistry. About this Book... Volume 1, devoted solely to the vital research area concerning the role of metal ions in neurodegenerative diseases, offers in 15 stimulating chapters an authoritative and timely view of this fascinating subject. Written by 41 internationally recognized experts, Neurodegenerative Diseases and Metal Ions highlights, supported by 130 illustrations, the recent progress made in understanding the role metal ions play in diseases like transmissible spongiform encephalopathies (Creutzfeldt-Jakob and related diseases), Alzheimer's, Parkinson's, Huntington's, Wilson's and Menkes' diseases, as well as in familial amyotrophic lateral sclerosis and others. The interplay between metal ions, catecholamines and the formation of reactive oxygen species resulting in oxidative stress is considered, as is the metalloneurochemistry of zinc and the neurotoxicity of aluminum, cadmium, lead, and mercury. The need for novel drugs which manipulate metal-centered neuropathology is emphasized.

Metal ions in the brain are a necessity as well as a poison. The presence of metal ions in the active sites of biological catalysts or metalloproteins and in the biological functioning of nucleic acids is very well documented and they are required for brain activity. On the other hand, metals are very effective in generating oxidative stress. This effect does not only play a role in immunology but also is the root of practically all neurodegenerative disorders by inducing disease via the death of neurons. Managing metal ions in the brain could therefore be an important strategy in the search for therapeutic agents used in the treatment of neurodegenerative diseases. This new title gives an overview to key topics in the area of metal ions in the brain. It focuses on the role of metal ions in neurological systems by describing their advantageous functions as well as their poisonous features. It is therefore of interest for scientists in biochemistry and biophysics, physiology, toxicology as well as for physicians focused on this topic.

Neurodegenerative diseases of the human brain appear in various forms, resulting in disorders of movement and coordination, cognitive deterioration and psychiatric disturbances. Many of the key factors leading to neurodegenerative diseases are similar, including the dysfunction of metal ion homeostasis, redox-active metal ions generating oxidative stress, and intracellular inclusion bodies. Metal-based Neurodegeneration presents a detailed survey of the molecular origins of neurodegenerative diseases. Each chapter is dedicated to a specific disease, presenting the latest scientific findings, including details of their biochemical actors (proteins or peptides), their normal and pathological conformations, and a description of the diseases characteristics, with an emphasis on the role of metal-induced oxidative stress, which can result in the production of intracellular aggregates of target proteins and peptides. Topics covered include: Brain function, physiology and the blood-brain barrier Immune system and neuroinflammation Aging and mild cognitive impairment, MCI Parkinson’s Disease Alzheimer’s Disease Creutzfelt-Jakob and related prion diseases Alcoholic Brain Damage Therapeutic strategies to combat the onset and progression of neurological diseases This extensively updated, full colour, second edition of Metal-based Neurodegeneration is an essential text for research scientists and clinicians working in gerontology, neuropathology, neurochemistry, and metalloprotein mechanisms.

About the Series... Metal Ions in Life Sciences links coordination chemistry and biochemistry in their widest sense and thus increases our understanding of the relationship between the chemistry of metals and life processes. The series reflects the interdisciplinary nature of Biological Inorganic Chemistry and coordinates the efforts of scientists in fields like biochemistry, inorganic chemistry, coordination chemistry, molecular and structural biology, enzymology, environmental chemistry, physiology, toxicology, biophysics, pharmacy, and medicine. Consequently, the volumes are an essential source for researchers active in these and related fields as well as teachers preparing courses, e.g., in Bioinorganic Chemistry. About this Book... Volume 1, devoted solely to the vital research area concerning the role of metal ions in neurodegenerative diseases, offers in 15 stimulating chapters an authoritative and timely view of this fascinating subject. Written by 41 internationally recognized experts, Neurodegenerative Diseases and Metal Ions highlights, supported by 130 illustrations, the recent progress made in understanding the role metal ions play in diseases like transmissible spongiform encephalopathies (Creutzfeldt-Jakob and related diseases), Alzheimer's, Parkinson's, Huntington's, Wilson's and Menkes' diseases, as well as in familial amyotrophic lateral sclerosis and others. The interplay between metal ions, catecholamines and the formation of reactive oxygen species resulting in oxidative stress is considered, as is the metalloneurochemistry of zinc and the neurotoxicity of aluminum, cadmium, lead, and mercury. The need for novel drugs which manipulate metal-centered neuropathology is emphasized.

Bioinorganic chemistry has a cross disciplinary approach, applying the principles of chemistry to biological systems. Metallochemistry of Neurodegeneration: Biological, Chemical and Genetic Aspects discusses the rapidly developing area of metals in the nervous system and their role in neurodegenerative disease, such as Alzheimer's, Parkinson's and prion diseases. Written by leading experts in their fields, each chapter combines elements of genetics, biochemistry and biological inorganic chemistry in its discussion. The book highlights the differences in pathologies of neurodegenerative diseases but also discusses the mechanistic similarities. Sections include: metal ions and prion diseases; metal ions and Alzheimer disease; manganese in brain functioning; metal involvement in Parkinson disease; Cu-Zn superoxide dismutase and familial amyotrophic lateral sclerosis. This book will appeal to both chemists and biologists at the post graduate and research level.

This exciting new book opens a window into the causes of debilitating neurological disorders such as Parkinson’s disease, CJD and Huntington’s disease, and gives indications of the prospects for therapy, based on the understanding of molecular defects involved in these diseases. Looking at each specific neurological disorder in turn, the book outlines the role of metals in human biology, in particular in the brain and explores tools for testing potential therapeutic strategies. It concludes with an overview of the potential of both chelation and antioxidant therapy and outlines some perspectives for the future.

The purpose of this book is to bring together scientists and clinicians interested in oxidative injury in the nervous system but whose approaches to investigation and treatment design vary widely. Indeed the goal of this book is to show that the investiga tive approaches and potential therapeutic interventions perhaps do not vary as widely as some may think. I think that the readers of this book will not read it from front to back, but will pick chapters of interest. Thus, the chapters are organized to contain information that is essential to understanding basic aspects of oxidative injury, and thus have some redundancy. However, within the context of each chapter the reader should hopefully find impetus and direction to go on to another chapter. The book is divided into three seetions. The first section contains reviews of metals and their role in generating oxidative injury. lron is considered in three of these chapters because of its relative abundance in the brain and its potency in inducing free radicals. The second section focuses on mechanisms by which the brain attempts to protect itself from oxidative injury. Some of these mechanisms have the potential to be protective in some situations and potentiaIly damaging in others. The third section contains the clinicaI diseases in which oxidative injury is known to contribute to the pathogenic process. This seetion ends with a chapter on antioxidant therapeutic strate gies in neurological disorders.