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Author : Sarah Pickles
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (13 download)
Download or read book Uncovering the Role of Misfolded SOD1 in the Pathogenesis of Amyotrophic Lateral Sclerosis written by Sarah Pickles and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Seiichi Nagano
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (115 download)
Download or read book Role of Cysteine Residue of Mutant Cu, Zn-Superoxide Dismutase (SOD1) in the Pathogenesis of Amyotrophic Lateral Sclerosis (ALS) written by Seiichi Nagano and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Mutations of Cu, Zn-superoxide dismutase (SOD1) gene have been identified in a subset of familial amyotrophic lateral sclerosis (ALS). Conformational change, that is, misfolding, of mutant SOD1 underlies its toxic gain of function for motor neuronal degeneration. Mutant SOD1 is prone to cause oxidative stress through the copper exposed on the protein by misfolding. The protein structure of SOD1 is critically affected by the redox state of cysteine residues, especially of Cys111. Oxidative modification of Cys111, which is enhanced in mutant SOD1, causes destabilization of the dimer interface to promote misfolding and aggregation of the protein. Substitution of Cys111 to serine alleviated the degeneration of motor neurons as well as the misfolding and aggregate formation of mutant SOD1 in the spinal cord of transgenic mice. It indicates that Cys111 is a crucial residue for the pathogenesis of ALS by mutant SOD1.
Author : Rishi Rakhit
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (13 download)
Download or read book Cu/Zn Superoxide Dismutase Misfolding in Amyotrophic Lateral Sclerosis written by Rishi Rakhit and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Ting Zhou
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (135 download)
Download or read book Selective Knockdown of Misfolded SOD1 as a Therapy for Amyotrophic Lateral Sclerosis written by Ting Zhou and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that features progressive degeneration of motor neurons. Over the past two decades, a major breakthrough in ALS research is the discovery that mutations in the gene superoxide dismutase 1 (SOD1) are a cause of familial ALS (fALS). Strong evidence supports that the fFALS-linked SOD1 variants are readily susceptible to posttranslational modifications, and subsequently become misfolded. Accumulation of the misfolded SOD1 triggers a toxic cascade leading to motor neuron degeneration. Studies also show that the wild type (WT) human SOD1, when modified post-translationally, undergoes aberrant conformational changes and acquires the same toxic properties that are observed in fALS-associated SOD1 variants. Misfolded SOD1 is thus at the center of ALS pathogenesis and a common toxic factor to a subset of both familial and sporadic ALS. Targeting misfolded SOD1 is therefore a rational approach towards an effective treatment for ALS. Here I present a new approach to selectively knockdown misfolded SOD1 by insertion of the CT-4 epitope of Derlin-1 into the chaperone-mediated autophagy system (CMA). In this study, I report efficiency and specificity of CT-4 peptide in knocking down misfolded SOD1 in vitro and in vivo. Our results revealed that CT-4 treatment resulted in a selective degradation of misfolded SOD1 in a dose-, time- and lysosomal activity-dependent manner in vitro. The in vivo studies revealed that CT-4 treatment resulted in knockdown of misfolded SOD1 in the tissues from the G93A transgenic mouse model of ALS. In addition, daily injection of CT-4 peptide significantly attenuated loss of motor neurons, delayed disease onset and extended lifespan of G93A transgenic mice of ALS. Furthermore, I explored the potential mechanisms underlying which CT-4 peptide delayed disease onset. My data indicated that knockdown of misfolded SOD1 could directly affect monocarboxylate transporter 1 (MCT1) protein expression in spinal cord, suggesting that CT-4 peptide treatment could result in preservation of MCT1 expression, maintenance of axon myelin and protection of neurons in ALS animal model. Therefore, the peptide may be developed into an effective treatment for ALS.
Author : Lawrence H. Lash
Publisher : Elsevier
ISBN 13 : 1483218619
Total Pages : 527 pages
Book Rating : 4.4/5 (832 download)
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.
Author : Rishi Rakhit
Publisher :
ISBN 13 : 9780494591352
Total Pages : 494 pages
Book Rating : 4.5/5 (913 download)
Download or read book Copper, Zinc Superoxide Dismutase Misfolding in Amyotrophic Lateral Sclerosis written by Rishi Rakhit and published by . This book was released on 2009 with total page 494 pages. Available in PDF, EPUB and Kindle. Book excerpt: Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration resulting in progressive paralysis and death. The only known cause of typical ALS is mutations in SOD1; these predominantly missense mutations produce a toxic gain-of-function in the enzyme Cu/Zn superoxide dismutase (SOD1). The prevailing hypotheses regarding the mechanism of toxicity were (a) oxidative damage from aberrant SOD1 redox chemistry, and (b) misfolding of the mutant protein. The goal of this thesis was to investigate the molecular mechanisms of the mutant SOD1 (mSOD1) misfolding and toxicity.To interrogate the in vivo misfolding pathway of SOD1, we used its high-resolution structure to create an antibody that reacts with monomer/misfolded SOD1 but not the native dimer. Upon verifying the reactivity of this antibody, we showed that monomer/misfolded SOD1 is found in a human case of familial ALS and in transgenic animal models of ALS. Misfolded SOD1 is found primarily in affected cells, motor neurons. Misfolded SOD1 is also initially absent, but appears prior to symptom onset. These observations together suggest a causal role for SOD1 misfolding through a monomeric intermediate in ALS pathogenesis.Because oxidation of SOD1 primarily affected the metal-binding His residues, we hypothesized that oxidation of wild-type, holo-SOD1 should lead to aggregation. Increasing the concentration of wild-type SOD1 in oxidation reactions produced aggregates similar to those observed earlier. Both wild-type and mSOD1 aggregation kinetics revealed an initial decrease in particle size rather than a monotonic increase using dynamic light scattering. This was consistent with the conversion of SOD1, normally an obligate homodimer, into monomers prior to aggregation. This observation was confirmed using analyatical ultracentrifugation. The common aggregation pathway for wild-type and mSOD1 suggested a mechanism for sporadic ALS caused by SOD1 misfolding.We proposed that oxidative damage to SOD1 itself could cause its misfolding and aggregation. To investigate this hypothesis, we subjected purified SOD1 in vitro to metal catalyzed oxidation. Oxidation of SOD1 produced aggregates reminiscent of those observed in ALS pathology. Aggregation propensity of zinc-deficient SOD1 and several mSOD1s known to have lower zinc-binding affinity was proportional to partial unfolding. Oxidation of SOD1 caused conversion of several His residues to 2-oxo-histidine.
Author : Humberto Foyaca Sibat
Publisher : BoD – Books on Demand
ISBN 13 : 9535126008
Total Pages : 281 pages
Book Rating : 4.5/5 (351 download)
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.
Author : Stephen J. Lippard
Publisher : University Science Books
ISBN 13 : 9780935702729
Total Pages : 444 pages
Book Rating : 4.7/5 (27 download)
Download or read book Principles of Bioinorganic Chemistry written by Stephen J. Lippard and published by University Science Books. This book was released on 1994 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: The use of unnatural metals - which have been introduced into human biology as diagnostic probes and drugs - is another active area of tremendous medical significance.
Author : Gabor G. Kovacs
Publisher : Cambridge University Press
ISBN 13 : 1316337650
Total Pages : 320 pages
Book Rating : 4.3/5 (163 download)
Download or read book Neuropathology of Neurodegenerative Diseases written by Gabor G. Kovacs and published by Cambridge University Press. This book was released on 2017-12-13 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: This practical guide to the diagnosis of neurodegenerative diseases discusses modern molecular techniques, morphological classification, fundamentals of clinical symptomology, diagnostic pitfalls and immunostaining protocols. It is based on the proteinopathy concept of neurodegenerative disease, which has influenced classification and provides new strategies for therapy. Numerous high-quality images, including histopathology photomicrographs and neuroradiology scans, accompany the description of morphologic alterations and interpretation of immunoreactivities. Diagnostic methods and criteria are placed within recent developments in neuropathology, including the now widespread application of immunohistochemistry. To aid daily practice, the guide includes diagnostic algorithms and offers personal insights from experienced experts in the field. Special focus is given to the way brain tissue should be handled during diagnosis. This is a must-have reference for medical specialists and specialist medical trainees in the fields of pathology, neuropathology and neurology working with neuropathologic features of neurodegenerative diseases.
Author : Marina Ramirez-Alvarado
Publisher : John Wiley & Sons
ISBN 13 : 1118031814
Total Pages : 1311 pages
Book Rating : 4.1/5 (18 download)
Download or read book Protein Misfolding Diseases written by Marina Ramirez-Alvarado and published by John Wiley & Sons. This book was released on 2010-12-01 with total page 1311 pages. Available in PDF, EPUB and Kindle. Book excerpt: An increasingly aging population will add to the number of individuals suffering from amyloid. Protein Misfolding Diseases provides a systematic overview of the current and emerging therapies for these types of protein misfolding diseases, including Alzheimer's, Parkinson's, and Mad Cow. The book emphasizes therapeutics in an amyloid disease context to help students, faculty, scientific researchers, and doctors working with protein misfolding diseases bridge the gap between basic science and pharmaceutical applications to protein misfolding disease.
Author : Sarika Singh
Publisher : Springer
ISBN 13 : 9811309442
Total Pages : 302 pages
Book Rating : 4.8/5 (113 download)
Download or read book Pathology, Prevention and Therapeutics of Neurodegenerative Disease written by Sarika Singh and published by Springer. This book was released on 2018-09-24 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, written by a leading panel of experts in the field of neurosciences, provides a comprehensive overview of the pathology of neurodegenerative diseases as well as the preventive measures. Prevention is important due to the lack of early diagnostic markers and the limitations/ problems of treating neurodegenerative diseases
Author : William Duddy
Publisher :
ISBN 13 : 9783036516219
Total Pages : 318 pages
Book Rating : 4.5/5 (162 download)
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.
Author : Rita Sattler
Publisher : Springer
ISBN 13 : 331989689X
Total Pages : 321 pages
Book Rating : 4.3/5 (198 download)
Download or read book RNA Metabolism in Neurodegenerative Diseases written by Rita Sattler and published by Springer. This book was released on 2018-06-18 with total page 321 pages. Available in PDF, EPUB and Kindle. Book excerpt: It has become evident over the last years that abnormalities in RNA processing play a fundamental part in the pathogenesis of neurodegenerative diseases. Cellular viability depends on proper regulation of RNA metabolism and subsequent protein synthesis, which requires the interplay of many processes including transcription, pre--‐mRNA splicing, mRNA editing as well as mRNA stability, transport and translation. Dysfunction in any of these processes, often caused by mutations in the coding and non--‐ coding RNAs, can be very destructive to the cellular environment and consequently impair neural viability. The result of this RNA toxicity can lead to a toxic gain of function or a loss of function, depending on the nature of the mutation. For example, in repeat expansion disorders, such as the newly discovered hexanucleotide repeat expansion in theC9orf72 gene found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a toxic gain of function leads to the formation of RNA foci and the sequestration of RNA binding proteins (RBPs). This in return leads to a loss of function of those RBPs, which is hypothesized to play a significant part in the disease progression of ALS and FTD. Other toxicities arising from repeat expansions are the formation of RNA foci, bi--‐directional transcription and production of repeat associated non--‐ATG (RAN) translation products. This book will touch upon most of these disease mechanisms triggered by aberrant RNA metabolism and will therefore provide a broad perspective of the role of RNA processing and its dysfunction in a variety of neurodegenerative disorders, including ALS, FTD, Alzheimer’s disease, Huntington’s disease, spinal muscular atrophy, myotonic dystrophy and ataxias. The proposed authors are leading scientists in the field and are expected to not only discuss their own work, but to be inclusive of historic as well as late breaking discoveries. The compiled chapters will therefore provide a unique collection of novel studies and hypotheses aimed to describe the consequences of altered RNA processing events and its newest molecular players and pathways.
Author : Thomas T. Warner
Publisher : Elsevier Health Sciences
ISBN 13 : 0702038458
Total Pages : 343 pages
Book Rating : 4.7/5 (2 download)
Download or read book Practical Guide to Neurogenetics E-Book written by Thomas T. Warner and published by Elsevier Health Sciences. This book was released on 2008-11-04 with total page 343 pages. Available in PDF, EPUB and Kindle. Book excerpt: This simple guide to neurogenetics demystifies the overwhelming amount of information on the subject so you can identify key clinical features and understand your management options. Reach relevant differential diagnoses and provide appropriate counseling to your patients using the symptom-based approach. By integrating genetic and neurological approaches to diagnoses, this book ensures that the neurological consequences of a genetic diagnosis and the genetic consequences of a neurological diagnosis are clear and explicit. Concise and portable, this book is ideal for easy reference in clinical use. Details the underlying basic science and clinical features of genetic disorders by taking a symptom-based approach to provide you with a comprehensive understanding of the field. Focuses on the clinical application of neurogenetics to be of practical use to you in the clinic. Clarifies the neurological consequences of a genetic diagnosis and the genetic consequences of a neurological diagnosis by integrating genetic and neurological approaches to diagnoses. Discusses and evaluates necessary investigations so you know when to use them and when to refer. Highlights diagnostic and therapeutic tips so you can learn new concepts or refine your skills in practice. Refers to online sources, such as Online Mendelian Inheritance in Man (OMIM) and others, to help you supplement your knowledge.
Author : Tsuneya Ikezu
Publisher : Springer
ISBN 13 : 3319440225
Total Pages : 1045 pages
Book Rating : 4.3/5 (194 download)
Download or read book Neuroimmune Pharmacology written by Tsuneya Ikezu and published by Springer. This book was released on 2016-12-22 with total page 1045 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of Neuroimmune Pharmacology bridges the disciplines of neuroscience, immunology and pharmacology from the molecular to clinical levels with particular thought made to engage new research directives and clinical modalities. Bringing together the foremost field authorities from around the world, Neuroimmune Pharmacology will serve as an invaluable resource for the basic and applied scientists of the current decade and beyond.
Author : Roberto Scatena
Publisher : Springer Science & Business Media
ISBN 13 : 9400728697
Total Pages : 459 pages
Book Rating : 4.4/5 (7 download)
Download or read book Advances in Mitochondrial Medicine written by Roberto Scatena and published by Springer Science & Business Media. This book was released on 2012-03-08 with total page 459 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria are far more than the “powerhouse” of the cell as they have classically been described. In fact, mitochondria biological activities have progressively expanded to include not only various bioenergetic processes but also important biosynthetic pathways, calcium homeostasis and thermogenesis, cell death by apoptosis, several different signal transduction pathways mainly related to redox control of gene expression and so on. This functional and structural complexity may undergo important derangements so to justify the definition of ‘mitochondrial medicine’, which should include all the clinical consequences of congenital or acquired mitochondrial dysfunctions. There are actually a growing number of studies which assign a significant pathogenic role to damaged mitochondria in different diseases: ischemia/reperfusion injury, neurodegenerative diseases, cancer with its dramatic sequelae (i.e, metastasis), metabolic syndrome, hyperlipidemias, just to mention a few of the most important pathologies. In this context, a further aspect that should not be disregarded is the interaction of pharmacological agents with mitochondria, not only in regard of the toxicological aspects but, above all, of the potential therapeutic applications. In fact, it is interesting to note that, while the properties of different so-called “mitoxicants” are well-known, the subtle linkages between drugs and mitochondria is still in need of a real pharmacological and therapeutic control at the clinical level. This lack of consideration can often lead to an underestimation of unwanted toxic effects but also of desirable therapeutic activities. A reevaluation of the potential clinical role of mitochondria could give a new light on some yet obscure aspects of human pathophysiology.
Author : Nancy Y. Ip
Publisher : Springer Science & Business Media
ISBN 13 : 0387788875
Total Pages : 326 pages
Book Rating : 4.3/5 (877 download)
Download or read book Cyclin Dependent Kinase 5 (Cdk5) written by Nancy Y. Ip and published by Springer Science & Business Media. This book was released on 2009-02-28 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.
