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Aluminium is a chemical element present in earth’s crust and it is a known environmental toxin which has been found to be associated with various neurological disorders. Aluminium has been found to be a very strong risk factor for the development of Alzheimer’s disease. Biochemical Mechanisms of Aluminium Induced Neurological Disorders explains the association of aluminium with neurological disorders. The book introduces the reader to sources of aluminium exposure, followed by an explanation of pharmacokinetics of aluminium and the different biochemical pathways that cause neurological effects. Chapters cover the typical mechanisms associated with aluminium neurotoxicity such as synaptic impairment as well as recent topics of interest such as the role of aluminum in impairing blood-brain barrier functions. Separate chapters which cover clinical evidence of aluminium toxicity and its management are also included in the book. Biochemical Mechanisms of Aluminium Induced Neurological Disorders is a concise, yet informative reference on the subject of aluminium neurotoxicity for all readers, whether they are students of biochemistry, pharmacology and toxicology, clinical neurologists, environmentalists interested in metal pollution or general readers who want to learn about the toxic effects of aluminium in humans.
Aluminum is the third most abundant element in the Earth's crust. In many of the previous experimental, epidemiological, pathohistological, biochemical and other research studies, aluminum, accumulated from the environment has been recognized as a very harmful substance to the human body. Aluminum intake usually happens unintentionally due to the fact that people know little about its prevalence in water, factory-processed foods, medicines, cosmetics, etc. When accumulated in human organs, it can cause severe damage, and even lead to chronic neurodegenerative diseases. Both oxidative and nitrosative stress can be the leading cause or contribute to its toxic effects in humans and animals. All of this is supported by the fact that mitochondrial dysfunction is the earliest stage of aluminum neurotoxicity. When oxidative damage occurs under the effects of free radicals, together with the decreased antioxidant protection due to the decreased production of the chemical energy molecule (adenosine triphosphate) as well as reducing equivalents (both in and out of mitochondria) then the conditions for the occurrence of a vicious circle in aluminum neurotoxicity are created. Aluminum also significantly interferes with the main steps of the synaptic neurotransmission, which may lead to the progression of neuropathies. The glutamate-glutamine pathway and numerous neurotransmitter transporters are affected as well. Oxidative stress and the disruption of neurotransmission do not only exist when adult individuals are exposed to this neurotoxin, but also in individuals prenatally exposed to it as well, and these are expressed after birth. Numerous research studies, both in animals and humans, ex vivo and in vitro, quite clearly showed that aluminum can be associated with chronic neurodegenerative diseases. Additionally, there is a positive correlation between the exposure to aluminum and the pathophysiology of Alzheimer's, Parkinson's, Huntington's disease, amyotrophic lateral sclerosis, and so on. One of the possible mechanisms for the generation/development of these diseases could be the disturbed homeostasis of essential metals and the appearance of unfolded or misfolded proteins that are mostly specific for a particular disease. In those research studies, the influence of aluminum on the generation of beta-amyloid, alpha synuclein, etc. was satisfactorily examined. It is very difficult, however, to suppress aluminum neurotoxicity, as well as development and progression of the diseases caused by or associated with aluminum. This is the result of some complex mechanisms through which aluminum causes its deleterious effects, and which are also responsible for the existence of multiple targets for aluminum. It is, therefore, necessary to know how these mechanisms induce the damage, in order to be able to prevent or treat the damage once it occurs. A large number of substances, including active components in traditional medicine, medical drugs and substances which are used only experimentally, have been examined so far. The results of studies conducted so far are inconclusive and they require further research. According to all the aforementioned findings, it may be concluded that well-planned, prospective and randomized clinical trials are necessary in order to use any of these substances in humans.
The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.
Phytochemicals are naturally occurring bioactive compounds found in edible fruits, plants, vegetables, and herbs. Unlike vitamins and minerals, phytochemicals are not needed for the maintenance of cell viability, but they play a vital role in protecting neural cells from inflammation and oxidative stress associated with normal aging and acute and chronic age-related brain diseases. Neuroprotective Effects of Phytochemicals in Neurological Disorders explores the advances in our understanding of the potential neuroprotective benefits that these naturally occurring chemicals contain. Neuroprotective Effects of Phytochemicals in Neurological Disorders explores the role that a number of plant-based chemical compounds play in a wide variety of neurological disorders. Chapters explore the impact of phytochemicals on neurotraumatic disorders, such as stroke and spinal cord injury, alongside neurodegenerative diseases such as Alzheimer's and Parkinson's Disease, as well as neuropsychiatric disorders such as depression and schizophrenia. The chapters and sections of this book provide the reader with a big picture view of this field of research. Neuroprotective Effects of Phytochemicals in Neurological Disorders aims to present readers with a comprehensive and cutting edge look at the effects of phytochemicals on the brain and neurological disorders in a manner useful to researchers, neuroscientists, clinical nutritionists, and physicians.
To understand Alzheimer's disease (AD) is one of the major thrusts of present-day clinical research, strongly supported by more fimdamental cellular, biochemical, immunological and structural studies. It is these latter that receive attention within this book. This compilation of 20 chapters indicates the diversity of work currently in progress and summarizes the current state of knowledge. Experienced authors who are scientifically active in their fields of study have been selected as contributors to this book, in an attempt to present a reasonably complete survey of the field. Inevitably, some exciting topics for one reason or another have not been included, for which we can only apologize. Standardization of terminology is often a problem in science, not least in the Alzheimer field; editorial effort has been made to achieve standardization between the Chapters, but some minor yet acceptable personal / author variation is still present, i. e. P-amyloid/amyloid-P; Ap42/Apl-42/APi. 42! The book commences with a broad survey of the contribution that the range of available microscopical techniques has made to the study of Alzheimer's amyloid plaques and amyloid fibrillogenesis. This chapter also serves as an Introduction to the book, since several of the topics introduced here are expanded upon in later chapters. Also, it is significant to the presence of this chapter that the initial discovery of brain plaques, by Alois Alzheimer, utilized light microscopy, a technique that continues to be extremely valuable in present-day AD research.
Due to that at present, the majority of diseases are associated with alterations in oxidative stress and inflammatory processes, and in that Nrf-2 is a modulator of these processes; knowing how this transcriptional factor functions and is regulated opens a therapeutic window to diverse diseases. Therefore, the efforts of various investigation groups are centered on finding activators and/or inhibitors of Nrf-2 to prevent or control diverse diseases, for example, cancer, where it would be important to regulate Nrf-2 in order for it to activate apoptosis pathways in cancerogenous cells, or in neurodegenerative diseases where cell death is predominant, it would be important for Nrf-2 to activate antiapoptotic pathways.
The subject of aluminium and Alzheimer's disease has been plagued with controversy. This controversy has served to obscure much of the scientific research in this field, and subsequently has obscured the possibility that aluminium is a contributory factor in the aetiology of Alzheimer's disease. This book brings together many of the world's leading scientists researching aluminium and life and contains their critical summaries on the known facts about aluminium toxicity in man and to offer an opinion on the implications of this knowledge on a link between aluminium and Alzheimer's disease. The subject areas of the chapters were chosen to reflect the myriad of ways that aluminium is known to impact upon mammalian physiology and function and range from clinical studies, through animal models of disease to the detailed biochemistry of aluminium toxicity. Chapters are also included on epidemiology and other factors involved in the aetiology of Alzheimer's.This is the first time that this subject has been treated in such a comprehensive manner. The research detailed in each chapter, includes the latest research in the field, it has been critically appraised and this appraisal has been used by each author to present an informed opinion of its relevance to aluminium and Alzheimer's disease. The chapters are much more than reviews; they are a statement of the state of the art and of what the future may hold for research in this field. As a whole they show the high quality of research that has been carried out in our efforts to understand the toxicity of aluminium in man and that we are far away from discounting the possibility that aluminium is a contributory factor in the aetiology of Alzheimer's disease.
This book reviews the scientific literature and the authors’ own research linking aluminum neurotoxicity with cognitive impairment and Alzheimer’s disease (AD). It focuses on aluminum levels in the brain, region-specific and subcellular distribution, and its relation to neurofibrillary tangles and amyloid beta. Further, the book stresses the importance of aluminum’s complex speciation chemistry in relation to biology, and details aluminum’s mechanism in oxidative stress and cell death, especially in connection with apoptosis and necroptosis. The electrophysiological variation and synaptic plasticity induced by aluminum are covered, while the metal’s debatable role in AD and the cross-talk between aluminum and genetic susceptibility are also discussed. In closing, the book reviews the neurotoxic effects of aluminum and its important role in the pathogenesis of AD. Given its depth of coverage, the book provides readers with a systematic summary of aluminum neurotoxicity.
The report “Dementia: a public health priority” has been jointly developed by WHO and Alzheimer's Disease International. The purpose of this report is to raise awareness of dementia as a public health priority, to articulate a public health approach and to advocate for action at international and national levels.
Over 400 years ago, Swiss alchemist and physician Paracelsus (1493-1541) cited: "All substances are poisons; there is none that is not a poison. The right dose differentiates a poison from a remedy." This is often condensed to: "The dose makes the poison." So, why are we overtly anxious about intoxications?In fact, poisons became a global problem with the industrial revolution. Pesticides, asbestos, occupational chemicals, air pollution, and heavy metal toxicity maintain high priority worldwide, especially in developing countries. Children between 0 and 5 years old are the most vulnerable to both acute and chronic poisonings, while older adults suffer from the chronic effects of chemicals. This book aims to raise awareness about the challenges of poisons, to help clinicians understand current issues in toxicology.