Mechanisms And Metal Involvement In Neurodegenerative Diseases

Dementia and neurodegenerative diseases such as Parkinson’s and Alzheimer’s are becoming an increasingly important cause of medical and social concern due to the growth in the ageing population. Mechanisms and Metal Involvement in Neurodegenerative Diseases delivers in one volume a streamlined source of information on each of the main neurodegenerative diseases including mild cognitive impairment, Parkinson's, Alzheimer's, Freiderich's ataxia, prion disease, multiple sclerosis and alcoholic brain damage. Each chapter is structured to give the definition of disease, proteins involved with structure of normal protein and abnormal proteins, pathology associated with the abnormal proteins, oxidative stress and inflammation, iron homeostatic mechanisms, primary neurotransmitter involved, other metal involvement and therapeutic strategies. Structures of the adherent protein involved in the disease process are also presented with emphasis on the chemical structures used in the treatment of each neurodegenerative disease together with their biochemical mode of action. Written by acknowledged experts in their respective areas this new book provides readers with readily accessible information on each of the neurodegenerative diseases.

This exciting new book opens a window into the causes ofdebilitating neurological disorders such as Parkinson’sdisease, CJD and Huntington’s disease, and gives indicationsof the prospects for therapy, based on the understanding ofmolecular defects involved in these diseases. Looking at each specific neurological disorder in turn, the bookoutlines the role of metals in human biology, in particular in thebrain and explores tools for testing potential therapeuticstrategies. It concludes with an overview of the potential of bothchelation and antioxidant therapy and outlines some perspectivesfor the future.

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. 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

This issue reviews the role of metals in neurodegenerative diseases; including Parkinson’s and Huntington’s disease; restless leg syndrome and NBIA disorders; and Wilson’s disease and manganese and calcium accumulation disorders. An update on advances in neuroimaging and pathology of metal related disease is also presented. This volume of International Review of Neurobiology brings together cutting-edge research on metal related neurodegenerative disease It reviews the role of metals in neurodegenerative diseases, including Parkinson’s and Huntington’s disease; restless leg syndrome and NBIA disorders; and Wilson’s disease and manganese and calcium accumulation disorders An update on advances in neuroimaging and pathology of metal related disease is also presented

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 OC Metals and the Brain: From Neurochemistry to NeurodegenerationOCO (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. Contents: Metal-Catalyzed Redox Activity in Neurodegenerative Disease (M A Taddeo et al.); Aluminum and Central Nervous System Morphology in Hemodialysis (E Reusche); Transition Metals, Oxidation, Lipoproteins, and Amyloid-: Major Players in Alzheimer''s Disease (A Kontush); Molecular Basis of Copper Transport: Cellular and Physiological Functions of Menkes and Wilson Disease Proteins (ATP7A and ATP7B) (D R Kramer et al.); Copper-Zinc Superoxide Dismutase and Familial Amyotrophic Lateral Sclerosis (M B Yim et al.); Copper and Prion Disease (J Sasson & D Brown); Metallothioneins in Neurodegeneration (M Aschner et al.); Iron and Neurodegeneration (S L Grab & J R Connor); Iron, Neuromelanin, and -Synuclein in Neuropathogenesis of Parkinson''s Disease (K L Double et al.); Iron and Epilepsy (W-Y Ong et al.); Role of Iron Metabolism in Multiple Sclerosis (M J Kotze et al.); Neuroprotective Effects of Lithium (S Ermidiou-Pollet & S Pollet); and other articles. Readership: Academics, graduate students and researchers in neurology, psychiatry, neuroscience and environmental health."

Biometals such as copper, zinc and iron have key biological functions, however, aberrant metabolism can lead to detrimental effects on cell function and survival. These biometals have important roles in the brain, driving cellular respiration, antioxidant activity, intracellular signaling and many additional structural and enzymatic functions. There is now considerable evidence that abnormal biometal homeostasis is a key feature of many neurodegenerative diseases and may have an important role in the onset and progression of disorders such as Alzheimer’s, Parkinson’s, prion and motor neuron diseases. Recent studies also support biometal roles in a number of less common neurodegenerative disorders. The role of biometals in a growing list of brain disorders is supported by evidence from a wide range of sources including molecular genetics, biochemical studies and biometal imaging. These studies have spurred a growing interest in understanding the role of biometals in brain function and disease as well as the development of therapeutic approaches that may be able to restore the altered biometal chemistry of the brain. These approaches range from genetic manipulation of biometal transport to chelation of excess metals or delivery of metals where levels are deficient. A number of these approaches are offering promising results in cellular and animal models of neurodegeneration with successful translation to pre-clinical and clinical trials. At a time of aging populations and slow progress in development of neurotherapeutics to treat age-related neurodegenerative diseases, there is now a critical need to further our understanding of biometals in neurodegeneration. This issue covers a broad range of topics related to biometals and their role in neurodegeneration. It is hoped that this will inspire greater discussion and exchange of ideas in this crucial area of research and lead to positive outcomes for sufferers of these neurodegenerative diseases.

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.

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.