Download or read book Cellular and molecular mechanisms of motor neuron death in amyotrophic lateral sclerosis written by Ricardo Tapia and published by Frontiers Media SA. This book was released on 2015-02-11 with total page 191 pages. Available in PDF, EPUB and Kindle. Book excerpt: Amyotrophic lateral sclerosis (ALS), which was described since 1869 by Jean Martin Charcot, is a devastating neurodegenerative disease characterized by the selective and progressive loss of upper and lower motor neurons of the cerebral cortex, brainstem and the spinal cord. The cognitive process is not affected and is not merely the result of aging because may occur at young ages. The only known cause of the disease is associated with genetic mutations, mainly in the gene encoding superoxide dismutase 1 (familial ALS), whereas there is no known cause of the sporadic form of ALS (SALS), which comprises >90% of cases. Both ALS types develop similar histopathological and clinical characteristics, and there is no treatment or prevention of the disease. Because effective treatments for ALS, as for other neurodegenerative diseases, can only result from the knowledge of their cellular and molecular pathophysiological mechanisms, research on such mechanisms is essential. Although progress in neurochemical, physiological and clinical investigations in the last decades has identified several mechanisms that seem to be involved in the cell death process, such as glutamate-mediated excitotoxicity, alterations of inhibitory circuits, inflammatory events, axonal transport deficits, oxidative stress, mitochondrial dysfunction and energy failure, the understanding of the origin and temporal progress of the disease is still incomplete and insufficient. Clearly, there is a need of further experimental models and approaches to discern the importance of such mechanisms and to discover the factors that determine the selective death of motor neurons characteristic of ALS, in contrast to other neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. Whereas studies in vitro in cell cultures, tissue slices or organotypic preparations can give useful information regarding cellular and molecular mechanisms, the experiments in living animal models obviously reflect more closely the situation in the human disease, provided that the symptoms and their development during time mimics as close as possible those of the human disease. It is necessary to correlate the experimental findings in vitro with those in vivo, as well as those obtained in genetic models with those in non-genetic models, aiming at designing and testing therapeutic strategies based on the results obtained.

Download or read book Molecular and Cellular Therapies for Motor Neuron Diseases written by Nicholas M Boulis and published by Academic Press. This book was released on 2017-01-18 with total page 337 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular and Cellular Therapies for Motor Neuron Diseases discusses the basics of the diseases, also covering advances in research and clinical trials. The book provides a resource for students that will help them learn the basics in a detailed manner that is required for scientists and clinicians. Users will find a comprehensive overview of the background of Amyotrophic Lateral Sclerosis (ALS/Lou Gehrig’s Disease) and Spinal Muscular Atrophy (SMA), along with the current understanding of their genetics and mechanisms. In addition, the book details gene and cell therapies that have been developed and their translation to clinical trials. Provides an overview of gene and cell therapies for amyotrophic lateral sclerosis (ALS) and other motor neuron diseases Edited by a leading Neurosurgeon and two research scientists to promote synthesis between basic neuroscience and clinical relevance Presents a great resource for researchers and practitioners in neuroscience, neurology, and gene and cell therapy

Download or read book Amyotrophic Lateral Sclerosis written by Martin Henrik Maurer and published by BoD – Books on Demand. This book was released on 2012-01-20 with total page 742 pages. Available in PDF, EPUB and Kindle. Book excerpt: Though considerable amount of research, both pre-clinical and clinical, has been conducted during recent years, Amyotrophic Lateral Sclerosis (ALS) remains one of the mysterious diseases of the 21st century. Great efforts have been made to develop pathophysiological models and to clarify the underlying pathology, and with novel instruments in genetics and transgenic techniques, the aim for finding a durable cure comes into scope. On the other hand, most pharmacological trials failed to show a benefit for ALS patients. In this book, the reader will find a compilation of state-of-the-art reviews about the etiology, epidemiology, and pathophysiology of ALS, the molecular basis of disease progression and clinical manifestations, the genetics familial ALS, as well as novel diagnostic criteria in the field of electrophysiology. An overview over all relevant pharmacological trials in ALS patients is also included, while the book concludes with a discussion on current advances and future trends in ALS research.

Download or read book Understanding Neuromuscular Health and Disease Advances in Genetics Omics and Molecular Function written by William Duddy and published by . This book was released on 2021 with total page 318 pages. Available in PDF, EPUB and Kindle. Book excerpt: This compilation focuses on recent advances in the molecular and cellular understandingof neuromuscular biology, and the treatment of neuromuscular disease.These advances are at the forefront of modern molecular methodologies, oftenintegrating across wet-lab cell and tissue models, dry-lab computational approaches,and clinical studies. The continuing development and application ofmultiomics methods offer particular challenges and opportunities in the field,not least in the potential for personalized medicine.

Download or read book Novel Aspects on Motor Neuron Disease written by Humberto Foyaca Sibat and published by BoD – Books on Demand. This book was released on 2020-05-20 with total page 120 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dedicated to our readers, we include novel information (not reported in IntechOpen’s books before) about new contributions of aberrant astrocytes to MND damage and death in the SOD1G93A rat experimental model of ALS; novel genetic studies on ALS; an update of the structural and functional consequences of the spinal muscular atrophy-linked mutations of the survival motor neuron protein; stem cell therapy for MND; and the novel treatment for SMA and ALS in the introductory chapter. This book contains selected peer-reviewed chapters written by international researchers. In this publication, the readers will find a compilation of state-of-the-art reviews about etiology, therapies, investigations, the molecular basis of disease progression and clinical manifestations, and the genetic familial ALS, as well as novel therapeutic modalities. We look forward with confidence and pride to the remarkable role that this book will play for a new vision and mission.

Download or read book Amyotrophic Lateral Sclerosis written by Muralidhar L. Hegde and published by BoD – Books on Demand. This book was released on 2020-08-26 with total page 162 pages. Available in PDF, EPUB and Kindle. Book excerpt: A flurry of recent research on the role of the RNA/DNA-binding proteins TDP-43 and FUS as well as a dozen other factors (e.g., C9ORF72 and profilin) has led to a new paradigm in our understanding of the pathobiology of the motor neuron disease, Amyotrophic Lateral Sclerosis (ALS). How these factors trigger neuromuscular dysfunction is critical for developing more effective ALS therapeutics. The ‘gain-of-toxicity’ or ‘loss-of-function’ of these etiological factors is a key question. Recent studies on the imbalance in genome damage versus repair have opened avenues for potential DNA repair-based therapeutics. This book highlights emerging science in the area of ALS and discusses key approaches and mechanisms essential for developing a cure for ALS.

Download or read book A Study of the Mechanism of Motor Neuron Death in Amyotrophic Lateral Sclerosis written by Kristin Ann Politi and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Thus, I then used unbiased approaches, by meta-analyzing a gene expression signature captured from MNs undergoing cell death in vitro, to explore MN cell death drivers that may be engaged upstream or downstream to RIPK1/RIPK3/MLKL. I also explored the relevance of necroptosis to MN disease in vivo, in part by deleting RIPK3 from a genetic mouse model of familial ALS. Overall this approach did not rescue motor neuron loss, and there was no improvement in motor function, disease onset, or survival in these animals. I conclude that while necroptosis machinery drives motor neuron death in in vitro models of ALS, more work needs to be done to (1) assess the motor neuron-specific cell death program, and (2) evaluate the relationship, if any, of necroptosis to motor neuron disease in vivo.

Download or read book Current Advances in Amyotrophic Lateral Sclerosis written by Alvaro Estévez and published by BoD – Books on Demand. This book was released on 2013-09-11 with total page 268 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our understanding of the pathology of amyotrophic lateral sclerosis is a continuously changing field. New hypotheses are generated with each new discovery; they are abandoned to be reanalyzed after some time under the light of new observations. This book present a series of reviews from experts in different aspects of the disease focus on these hypotheses. There are also a few review chapters providing clear examples of these new observations that make the field to reanalyze previous conclusions.

Download or read book Molecular Mechanisms of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia written by Yulong Sun and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in modern medicine in the past century have dramatically improved the average life expectancy in the western world. Unfortunately, the molecular mechanisms that maintain the integrity of proteins in the body appear to be unable to keep pace. This has led to a growing prevalence of late-onset diseases involving abnormal accumulation of proteins, especially in the last century. The increase in occurrence of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and transmissible spongiform encephalopathies such as prion disease, has become a great burden to the healthcare system. All of these diseases are currently incurable and fatal, but they share the common hallmark of misfolding and aggregation of proteins within the effected neurons. The discovery and characterization of such proteins have often led to the identification of potential targets for treatment and drug design. In the case of ALS, progressive death of upper and lower motor neurons leads to full-body paralysis, and patient death from respiratory failure. The cause of ALS is currently unknown, but remarkably, regardless of the type of ALS (familial or sporadic), the RNA binding protein, TDP-43, is found in 97% of cases as neuronal inclusions, suggesting a mechanistic role in disease pathogenesis. In this thesis, several techniques are used to enable detailed biophysical characterization the TDP-43 aggregation process in solution and in model membranless organelles. Equilibrium turbidity measurements of the protein under aggregating conditions and the inhibitory effects of native-state stabilizing oligonucleotides on aggregation are presented. The modulatory effects of physiological concentrations of electrolytes on TDP-43 aggregation and their implications are also discussed. A novel technique called spatially targeted optical microproteomics (STOMP) is presented as a method to interrogate the proteomic contents of small cellular features in mammalian tissue in hope of identifying common proteins in neuronal inclusions and stress granules. Although the STOMP technique still requires refinement, the biophysical studies on TDP-43 presented here begin to unravel the complex and largely unknown etiology of what is currently a devastating and incurable disease.

Download or read book Clinical and Molecular Aspects of Motor Neuron Disease written by Johnathan Cooper-Knock and published by Morgan & Claypool. This book was released on 2013-09-01 with total page 62 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this e-book, motor neuron disease (MND) shall refer to amyotrophic lateral sclerosis (ALS), the most common neurodegenerative disorder affecting both the upper and lower motor neurons. With the discovery of C9ORF72 expansions in approximately 10% of all MND cases, in certain populations, we stand at the brink of a new era of MND research and hopefully treatment facilitated by the ability to associate a relatively large group of patients with a similar disease mechanism. This review will summarise both current clinical management of MND and our present understanding of the molecular pathogenesis of MND. Study of C9ORF72-MND has the potential to rapidly advance both of these aspects in the coming years. In the first section, we will discuss the clinical features of MND and describe how patients with this devastating condition present, are investigated, and managed in the 21st century. Although, currently, management is limited by an incomplete understanding of disease pathophysiology, there is much which can be done to assist and support patients with MND. In the following sections, we will discuss molecular mechanisms implicated in MND, highlighting observations which unify different theories. Particular attention will be given to placing proposed mechanisms within the clinical course of MND. Furthermore, novel therapeutic targets will be discussed. Table of Contents: Clinical Aspects of MND / Molecular Aspects of MND / References / Author Biographies / Titles of Related Interest / Series of Related Interest

Download or read book Molecular Mechanism and Therapeutics of Amyotrophic Lateral Sclerosis written by Koji Abe and published by Elsevier. This book was released on 2001 with total page 404 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume covers the latest findings on the molecular mechanism and therapeutics of amyotrophic lateral sclerosis (ALS), including important research on 1) pathological characteristics and epidemiology of ALS, 2) selective vulnerability of spinal motor neurons, 3) genetic abnormality of ALS and neurotrophin, 4) mechanism of motor neuron death and glutamate toxicity, 5) motor axon, axonal transport, neurofilament, and glycation, 6) basic therapeutic approach, and 7) clinical therapeutic approach. The surprising discovery of Cu/Zn superoxide dismutase (SOD1) gene mutations in a part of familial ALS in 1993 has had a strong impact on all neuroscientists and clinicians dealing with this disease. This volume aims to help them to progress their future basic and clinical investigations, and to enhance strong scientific collaboration in elucidating the molecular mechanism and discovering the essential therapeutics of the disease.

Download or read book Amyotrophic Lateral Sclerosis Motor Neuron Disease An Insight written by Thakur Gurjeet Singh and published by LAP Lambert Academic Publishing. This book was released on 2014-10-28 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: Amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig's disease, and rarely Charcot disease, is the most common form of motor neuron disease. It is typically characterized by degeneration of the motor neurons, and is usually fatal within a few years of onset. A subset of population suffering from ALS is due to inherited and genes mutation identified in familial cases have been involved in pathogenesis of ALS. Molecular mechanisms involved linked with SOD1-related ALS has revealed a complex array of interconnected pathological processes, including glutamate excitotoxicity, dysregulation of neurotrophic factors, axon guidance proteins, axonal transport defects, mitochondrial dysfunction, deficient protein quality control, and aberrant RNA processing. In humans, no therapy for ALS has ever been discovered that could extend lifespan more than a few additional months. The ALS Association has committed $99 million to find effective treatments and a cure for ALS. Our global research effort has helped increase the number of scientists working on ALS, advanced new discoveries and treatments, and has shed light on the complex genetic and environmental factors involved in ALS.

Download or read book Spectrums of Amyotrophic Lateral Sclerosis written by Christopher A. Shaw and published by John Wiley & Sons. This book was released on 2021-04-20 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt: SPECTRUMS OF AMYOTROPHIC LATERAL SCLEROSIS Discover state-of-the-art research findings on ALS from leading authors and editors in the field In Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis & Therapeutic Directions, distinguished researchers and editors Dr. Christopher A. Shaw and Jessica R. Morrice deliver a practical and powerful perspective on Amyotrophic Lateral Sclerosis (ALS) as a heterogeneous spectrum of disorders. This increasingly accepted point-of-view allows researchers and medical professionals to develop better targeted interventions and more precise therapies. In the book, readers will find chapters on a wide variety of critical issues facing ALS researchers and healthcare practitioners treating ALS sufferers, including animal models of ALS, neuronal support cells known to have a pivotal role in ALS, and current challenges in ALS clinical trials, among others. The authors describe pathologic features common to all cases of ALS and why animal models, though crucial, should be interpreted with caution. Finally, multiple genetic and environmental etiologies of the disease are discussed. Readers will also benefit from the inclusion of: A thorough introduction to ALS as a spectrum disease and the implications for models, therapeutic development and clinical trial design Explorations of the genetic basis of ALS, prospective sALS etiologies, and the involvement of microbiome in ALS Discussions of ALS-PDC and environmental risk factors, protein aggregation in ALS, defects in RNA metabolism in ALS, and the non-cell autonomous nature of ALS and the involvement of glial cells Examinations of animal models of ALS and perspectives on previously failed ALS therapeutics and current therapeutic strategies Perfect for clinical neurologists, healthcare providers and caretakers, clinicians, and researchers studying motor neuron disease, Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis & Therapeutic Directions is also an indispensable resource for the neurodegenerative research community, neurology residents, and graduate-level neuroscience students.

Download or read book Update on Amyotrophic Lateral Sclerosis written by Humberto Foyaca Sibat and published by BoD – Books on Demand. This book was released on 2016-09-14 with total page 281 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book contains selected peer-reviewed chapters which cover updated information on ALS written by international researchers. Update on Amyotrophic Lateral Sclerosis is comprised of 13 chapters from some of the world's top central nervous system researchers and neurologists to provide a timely review of the most recent developments in ALS, covering historic aspects, experimental animal models, genetics, pathogenesis, clinical aspects and imagenology among others. Contributors from Belgium, France, Japan, India, Italy, Mexico, Russia, South Africa, and Switzerland have collaborated enthusiastically and efficiently, dedicating their time to create this reader-friendly yet comprehensive work which includes many explanatory figures, tables and photos to enhance legibility and make the book clinically useful. We are looking forward with confidence and pride in the remarkable role that this book will play for a new vision and mission.

Download or read book Motor Neuron Disease in Adults written by Mark B. Bromberg and published by Contemporary Neurology. This book was released on 2014-10-28 with total page 369 pages. Available in PDF, EPUB and Kindle. Book excerpt: 'Motor Neuron Disease in Adults' reviews new information from 1998 as it applies to all aspects of motor neuron disease. Articles included use evidence-based methods to ensure that the new information is solid and advances the topic. The book can be used by anyone who provides any type of care to ALS patients.

Download or read book Mitochondrial Dysfunction written by Lawrence H. Lash and published by Elsevier. This book was released on 2013-10-22 with total page 527 pages. Available in PDF, EPUB and Kindle. Book excerpt: Methods in Toxicology, Volume 2: Mitochondrial Dysfunction provides a source of methods, techniques, and experimental approaches for studying the role of abnormal mitochondrial function in cell injury. The book discusses the methods for the preparation and basic functional assessment of mitochondria from liver, kidney, muscle, and brain; the methods for assessing mitochondrial dysfunction in vivo and in intact organs; and the structural aspects of mitochondrial dysfunction are addressed. The text also describes chemical detoxification and metabolism as well as specific metabolic reactions that are especially important targets or indicators of damage. The methods for measurement of alterations in fatty acid and phospholipid metabolism and for the analysis and manipulation of oxidative injury and antioxidant systems are also considered. The book further tackles additional methods on mitochondrial energetics and transport processes; approaches for assessing impaired function of mitochondria; and genetic and developmental aspects of mitochondrial disease and toxicology. The text also looks into mitochondrial DNA synthesis, covalent binding to mitochondrial DNA, DNA repair, and mitochondrial dysfunction in the context of developing individuals and cellular differentiation. Microbiologists, toxicologists, biochemists, and molecular pharmacologists will find the book invaluable.

Download or read book Glutathione In The Nervous System written by Christopher Ari Shaw and published by Routledge. This book was released on 2018-10-08 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: The goal of this text is to focus readers attention on three major areas; the origin and localization of GSH in the nervous system; the multiple effects of GSH on neural health activity; and the potential for alterations on GSH status to lead to neurological damage of the type observed in amyotrophic lateral sclerosis, Parkinson's disease and other neurological disorders. The text also touches upon the additional roles of the antoxidant GSH, including possible neurotransmitter action, redox modulation of ionotropic receptor function, and neuroprotection against exicitoxic actions of glutamate.