Download or read book The Molecular Mechanisms of Myelin Disassembly written by Marie-Theres Weil and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myelin is characterized by stacking of multiple layers of membrane compacted by MBP. The breakdown of myelin is a pathological hallmark of several autoimmune diseases of the nervous system. To assess the myelin fragmentation patterns in early stages of demyelinating disease, I employed antibody- and toxin-mediated animal models of Multiple Sclerosis and Neuromyelitis optica (NMO). Using electron microscopy of high pressure frozen samples, I could show that the temporary sequence of myelin degeneration in all the models employed starts with the vesiculation of the innermost myelin lamellae. ...

Download or read book Molecular Mechanisms of Myelin Dysfunctions in the Nervous System written by Jihyun Kim and published by . This book was released on 2017 with total page 166 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myelin is generated by Schwann cells (SCs) in the peripheral nervous system (PNS) and by oligodendrocytes (OLs) in the central nervous system (CNS). Myelin not only provides physical and structural support to the axon, it also provides trophic and metabolic supports. In addition, myelin is important for rapid nerve conduction, which is essential for proper communication within a neuronal circuit. Therefore, damage to myelin or myelin loss disrupts axonal integrity and impairs neuronal functions. Elucidating molecular mechanisms underlying myelin defects under pathological conditions will be important in gaining insights into developing a strategy for preventing myelin loss and improving myelin repair. In this study, we investigated molecular mechanisms of aberrant myelination and myelin loss associated with Charcot Marie Tooth disease (CMT) in the PNS and traumatic brain injury (TBI) in the CNS. In Chapter 1, we investigated the impact of CMT4B1-associated MTMR2 loss in SCs. CMT4B1 is a genetically inherited disorder of the PNS that is caused by loss of MTMR2 gene function. In CMT4B1 patients, myelin outfolding and demyelination are observed resulting in decreased nerve conduction, muscle weakness, atrophy, and sensory deficits. Previously, it has been shown that SC-specific deletion of MTMR2 in mice results in reduced nerve conduction and myelin abnormalities similar to defects observed in CMT4B1patients. However, the mechanism(s) by which loss of MTMR2 function leads to the myelin abnormalities are not fully understood. To elucidate the underlying mechanisms, we generated MTMR2 knockdown SCs and analyzed the effect of MTMR2 loss on intracellular signaling pathways that are essential for SC myelination. Since MTMR2 is a phosphoinositide 3-phosphatase that regulates the PI(3,5)P2 metabolism, it is possible that abnormal regulation of the PI(3,5)P2 level in MTMR2 KD SCs may be associated with the aberrant SC functions. Recently, PI(3,5)P2 has been shown to serve as a platform for mTORC1 signaling on lysosomal membrane. Since mTORC1 has an important role in SC myelination, we monitored whether MTMR2 loss affects the mTORC1 signaling pathway in SCs. Here, we report an aberrant increase in mTORC1 activity in MTMR2 KD SCs. The mTORC1 activation is also associated with inhibition of autophagy and transcription activity of TFEB, a regulator of lysosomal biogenesis and function. Myelin repair or promoting remyelination in the PNS is important for improving neuronal function in patients with peripheral myelin dysfunctions. In Chapter 2, we elucidated the promyelination function of recombinant TIMP-3 in SCs. TIMP-3 is a member of the tissue inhibitor of metalloproteinase family proteins and one of the targets includes ADAM17. Endogenous ADAM17 in the PNS negatively regulate axonal Nrg1 type III signaling that is essential for SC myelination. Here, we report that recombinant TIMP-3 enhances myelin formation by SCs. The TIMP-3 function is associated with an increase in axonal Nrg1 signaling and laminin deposition during the early stages of myelin formation. In Chapter 3, we investigated molecular mechanisms underlying myelin dysfunction in the CNS associated with TBI. Myelin loss following TBI contributes to axonal degeneration, neuronal death and in long-term, neuronal dysfunction in the patients. Recent studies provide evidence that primary myelin loss contributes to the myelinated axon pathology following TBI. The myelin loss appears to occur without OL death, indicating that demyelination results from a mechanism that actively destroys myelin in viable OLs. Therefore, understanding the mechanisms of OL response to injury may provide insights into preventing demyelination and/or to protecting proper axon- myelin units following TBI. To this end, we investigated the direct impact of mechanical injury on OLs. We developed an OL monoculture system established on a deformable silicone membrane that can be rapidly stretched by a computer-controlled air pulse, which mimics diffused mechanical injury in the brain following TBI. Our data show that stretch injury induces activation of the Erk1/2 pathway in OLs, which leads to myelin protein loss. Furthermore, the Erk1/2 activation was induced by intracellular calcium increase. Inhibition of Erk1/2 or chelating intracellular calcium prevents myelin protein loss after stretch injury. Furthermore, TBI in vivo results in rapid Erk1/2 activation in white matter OLs accompanied by losing the mature OL phenotype. By studying the molecular mechanisms responsible for myelin malformation or myelin loss in demyelinating diseases, we provide evidences of signaling pathways or signaling molecules that could be potential therapeutic targets for preventing myelin dysfunctions.

Download or read book Neuroproteomics written by Oscar Alzate and published by CRC Press. This book was released on 2009-10-26 with total page 356 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this, the post-genomic age, our knowledge of biological systems continues to expand and progress. As the research becomes more focused, so too does the data. Genomic research progresses to proteomics and brings us to a deeper understanding of the behavior and function of protein clusters. And now proteomics gives way to neuroproteomics as we beg

Download or read book Molecular Mechanisms of Myelin Membrane Biogenesis written by Katarina Trajkovic and published by . This book was released on 2007 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Biology of Oligodendrocytes written by Patricia Armati and published by Cambridge University Press. This book was released on 2010-10-21 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Traditionally, oligodendrocytes have been assumed to play a minor supporting role in the central nervous system and their importance has generally been overlooked. For the first time, this book provides a dedicated review of all of the major aspects of oligodendrocyte biology, including development, organization, genetics, and immunobiology. Later chapters emphasize the importance of this underestimated cell to the mammalian central nervous system by exploring the role of myelin synthesis and maintenance in neural disease and repair. Particular attention is paid to multiple sclerosis (MS), arguably the prime example of an acquired demyelinating disease, with detailed examinations of the current concepts regarding demyelination, oligodendroglial damage, and remyelination in MS lesions.

Download or read book Molecular Mechanisms Underlying MRNA Localization to Myelin Sheaths written by Katie Mae and published by . This book was released on 2018 with total page 192 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myelin is a specialized membrane produced by oligodendrocytes that insulates and supports axons. Oligodendrocytes extend numerous cellular processes, as projections of the plasma membrane, and simultaneously wrap multiple layers of myelin membrane around target axons. Notably, myelin sheaths originating from the same oligodendrocyte are variable in size, suggesting local mechanisms regulate myelin sheath growth. Purified myelin contains ribosomes and hundreds of mRNAs, supporting a model that mRNA localization and local protein synthesis regulate sheath growth and maturation. However, the mechanisms by which mRNAs are selectively enriched in myelin sheaths are unclear. To investigate how mRNAs are targeted to myelin sheaths, we tested the hypothesis that transcripts are selected for myelin enrichment through consensus sequences in the 3' untranslated region (3' UTR). Using methods to visualize mRNA in living zebrafish larvae, we identified candidate 3' UTRs that were sufficient to localize mRNA to sheaths and enriched near growth zones of nascent membrane. We bioinformatically identified motifs common in the 3' UTRs of three myelin-enriched transcripts and determined that these motifs are required for mRNA transport to myelin sheaths. Moreover, we show that one motif is highly enriched in the myelin transcriptome, suggesting that this sequence is a global regulator of mRNA localization during developmental myelination. In addition to localization sequences, we investigated how the RNA binding protein, Quaking, and neuronal activity promote mRNA localization to nascent sheaths. By identifying the cis-regulatory elements necessary to promote mRNA transport, we are uniquely poised to discover the trans-acting factors that interact with the elements. In this body of work, we investigated how RNA binding proteins (RBPs), promote myelination via post-transcriptional mRNA regulation and we anticipate these approaches will aid in the interrogation of novel RBPs that interact with the localization elements. Taken together, we identified several cis-regulatory elements that are required for mRNA localization to myelin sheaths, which provide the fundamental information necessary to determine how mRNA localization and local translation promote myelination.

Download or read book Neuroprotection in Alzheimer s Disease written by Illana Gozes and published by Academic Press. This book was released on 2016-12-30 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuroprotection in Alzheimer’s Disease offers a translational point-of-view from both basic and clinical standpoints, putting it on the cusp for further clinical development with its emphasis on nerve cell protection, including the accumulation of knowledge from failed clinical trials and new advances in disease management. This book brings together the latest findings, both basic, and clinical, under the same cover, making it easy for the reader to obtain a complete overview of the state-of-the-field and beyond. Alzheimer's disease is the most common form of dementia, accounting for 60 to 80 percent of dementia cases. It is a progressive brain disease that slowly destroys memory, thinking skills, and eventually, even the ability to carry out the simplest tasks. It is characterized by death of synapses coupled to death nerve cells and brain degeneration which is manifested by loss of cognitive abilities. Understanding neuroprotection in Alzheimer’s disease will pave the path to better disease management and novel therapeutics. Comprehensive reference detailing neuroprotection in Alzheimer’s Disease, with details on nerve cell protection and new advances in disease management Combines the knowledge and points-of-view of both medical doctors and basic scientists, putting the subject at the forefront for further clinical development Edited by one of the leading researchers in Alzheimer’s Disease

Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Netter s Atlas of Neuroscience written by David L. Felten and published by Elsevier Health Sciences. This book was released on 2015-11-30 with total page 499 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ideal for students of neuroscience and neuroanatomy, the new edition of Netter's Atlas of Neuroscience combines the didactic well-loved illustrations of Dr. Frank Netter with succinct text and clinical points, providing a highly visual, clinically oriented guide to the most important topics in this subject. The logically organized content presents neuroscience from three perspectives: an overview of the nervous system, regional neuroscience, and systemic neuroscience, enabling you to review complex neural structures and systems from different contexts. You may also be interested in: A companion set of flash cards, Netter's Neuroscience Flash Cards, 3rd Edition, to which the textbook is cross-referenced. Coverage of both regional and systemic neurosciences allows you to learn structure and function in different and important contexts. Combines the precision and beauty of Netter and Netter-style illustrations to highlight key neuroanatomical concepts and clinical correlations. Reflects the current understanding of the neural components and supportive tissue, regions, and systems of the brain, spinal cord, and periphery. Uniquely informative drawings provide a quick and memorable overview of anatomy, function, and clinical relevance. Succinct and useful format utilizes tables and short text to offer easily accessible "at-a-glance" information. Provides an overview of the basic features of the spinal cord, brain, and peripheral nervous system, the vasculature, meninges and cerebrospinal fluid, and basic development. Integrates the peripheral and central aspects of the nervous system. Bridges neuroanatomy and neurology through the use of correlative radiographs. Highlights cross-sectional brain stem anatomy and side-by-side comparisons of horizontal sections, CTs and MRIs. Features video of radiograph sequences and 3D reconstructions to enhance your understanding of the nervous system. Student Consult eBook version included with purchase. This enhanced eBook experience includes access -- on a variety of devices -- to the complete text, 14 videos, and images from the book. Expanded coverage of cellular and molecular neuroscience provides essential guidance on signaling, transcription factors, stem cells, evoked potentials, neuronal and glial function, and a number of molecular breakthroughs for a better understanding of normal and pathologic conditions of the nervous system. Micrographs, radiologic imaging, and stained cross sections supplement illustrations for a comprehensive visual understanding. Increased clinical points -- from sleep disorders and inflammation in the CNS to the biology of seizures and the mechanisms of Alzheimer's -- offer concise insights that bridge basic neuroscience and clinical application.

Download or read book Multiple Sclerosis written by Institute of Medicine and published by National Academies Press. This book was released on 2001-08-10 with total page 457 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is a chronic and often disabling disease of the nervous system, affecting about 1 million people worldwide. Even though it has been known for over a hundred years, no cause or cure has yet been discovered-but now there is hope. New therapies have been shown to slow the disease progress in some patients, and the pace of discoveries about the cellular machinery of the brain and spinal cord has accelerated. This book presents a comprehensive overview of multiple sclerosis today, as researchers seek to understand its processes, develop therapies that will slow or halt the disease and perhaps repair damage, offer relief for specific symptoms, and improve the abilities of MS patients to function in their daily lives. The panel reviews existing knowledge and identifies key research questions, focusing on: Research strategies that have the greatest potential to understand the biological mechanisms of recovery and to translate findings into specific strategies for therapy. How people adapt to MS and the research needed to improve the lives of people with MS. Management of disease symptoms (cognitive impairment, depression, spasticity, vision problems, and others). The committee also discusses ways to build and financially support the MS research enterprise, including a look at challenges inherent in designing clinical trials. This book will be important to MS researchers, research funders, health care advocates for MS research and treatment, and interested patients and their families.

Download or read book Cell Engineering and Regeneration written by Heinz Redl and published by Springer. This book was released on 2017-02-16 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This reference work presents the origins of cells for tissue engineering and regeneration, including primary cells, tissue-specific stem cells, pluripotent stem cells and trans-differentiated or reprogrammed cells. There is particular emphasis on current understanding of tissue regeneration based on embryology and evolution studies, including mechanisms of amphibian regeneration. The book covers the use of autologous versus allogeneic cell sources, as well as various procedures used for cell isolation and cell pre-conditioning , such as cell sorting, biochemical and biophysical pre-conditioning, transfection and aggregation. It also presents cell modulation using growth factors, molecular factors, epigenetic approaches, changes in biophysical environment, cellular co-culture and other elements of the cellular microenvironment. The pathways of cell delivery are discussed with respect to specific clinical situations, including delivery of ex vivo manipulated cells via local and systemic routes, as well as activation and migration of endogenous reservoirs of reparative cells. The volume concludes with an in-depth discussion of the tracking of cells in vivo and their various regenerative activities inside the body, including differentiation, new tissue formation and actions on other cells by direct cell-to-cell communication and by secretion of biomolecules.

Download or read book Biochemical Basis of Medicine written by Eric D. Wills and published by Butterworth-Heinemann. This book was released on 2014-04-24 with total page 654 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biochemical Basis of Medicine discusses academic biochemistry and the applications of biochemistry in medicine. This book deals with the biochemistry of the subcellular organelles, the biochemistry of the body , and of the specialized metabolism occurring in many body tissues. This text also discusses the various applications of biochemistry as regards environmental hazards, as well as in the diagnosis of illnesses and their treatment. This text explains the structure of the mammalian cell, the cell's metabolism, the nutritional requirements of the whole body, and the body's metabolism. This book explains the specialized metabolisms involved in tissues such as those occurring in blood clotting, in the liver during carbohydrate metabolism, or in the kidneys during water absorption. The text explains toxicology or biochemical damage caused by excess presence of copper, mercury, or lead in the body. Chelation therapy can remove these toxic metals. This book describes the effects of alcohol on plasma liquids, the multistage concept of carcinogenesis, and the biochemical basis of diagnosis. Diagnosis and treatment include the determination of typical enzymes found in the plasma, tests for genetic defects in blood proteins, and the use of chemotherapeutic drugs. This book is suitable for chemists, students and professors in organic chemistry, and laboratory technicians whose work is related to pharmacology.

Download or read book The Neuron written by Irwin B. Levitan and published by Oxford University Press, USA. This book was released on 2002 with total page 640 pages. Available in PDF, EPUB and Kindle. Book excerpt: Intended for use by advanced undergraduate, graduate and medical students, this book presents a study of the unique biochemical and physiological properties of neurons, emphasising the molecular mechanisms that generate and regulate their activity.

Download or read book Animal Models of Acute Neurological Injuries written by Jun Chen and published by Springer Science & Business Media. This book was released on 2008-12-16 with total page 490 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite numerous recent studies and exciting discoveries in the field, only limited treatment is available today for the victims of acute neurological injuries. Animal Models of Acute Neurological Injuries provides a standardized methodology manual designed to eliminate the inconsistent preparations and variability that currently jeopardizes advances in the field. Contributed by top experts and many original developers of the models, each chapter contains a step-by-step, proven procedure and visual aids covering the most commonly used animal models of neurological injury in order to highlight the practical applications of animal models rather than the theoretical issues. This intensive volume presents its readily reproducible protocols with great clarity and consistency to best aid neuroscientists and neurobiologists in laboratory testing and experimentation. Comprehensive and cutting-edge, Animal Models of Acute Neurological Injuries is an ideal guide for scientists and researchers who wish to pursue this vital course of study with the proficiency and precision that the field requires.

Download or read book The Axon written by Stephen G. Waxman and published by . This book was released on 1995 with total page 710 pages. Available in PDF, EPUB and Kindle. Book excerpt: The axon, interposed between the cell body and the synaptic terminals in most neurons, plays a crucial role in connecting neurons and acting as a conduit for the transmission of information between them. This book provides a comprehensive and up-to-date compendium that brings together chapterson the structure, function, and pathophysiology of axons in both the PNS and CNS. Carefully written, well-illustrated with superb illustrations, and generously referenced, the 33 chapters and introduction have been authored by 49 world-renowned authorities. Recent advances in the molecularneurobiology of axons are carefully reviewed, and new areas, such as the molecular biology of ion channels and myelination, the role of calcium in pathophysiology and regeneration, cell adhesion molecules and their roles in axo-glial interactions and axonal guidance, and optical recording methods,are highlighted. This book will provide an essential reference for neuroscientists as well as clinicians such as neurologists, neurosurgeons, and clinical electrophysiologists interested in axons.

Download or read book Brain Repair After Stroke written by Steven C. Cramer and published by Cambridge University Press. This book was released on 2010-10-28 with total page 307 pages. Available in PDF, EPUB and Kindle. Book excerpt: Increasing evidence identifies the possibility of restoring function to the damaged brain via exogenous therapies. One major target for these advances is stroke, where most patients can be left with significant disability. Treatments have the potential to improve the victim's quality of life significantly and reduce the time and expense of rehabilitation. Brain Repair After Stroke reviews the biology of spontaneous brain repair after stroke in animal models and in humans. Detailed chapters cover the many forms of therapy being explored to promote brain repair and consider clinical trial issues in this context. This book provides a summary of the neurobiology of innate and treatment-induced repair mechanisms after hypoxia and reviews the state of the art for human therapeutics in relation to promoting behavioral recovery after stroke. Essential reading for stroke physicians, neurologists, rehabilitation physicians and neuropsychologists.

Download or read book Multiple Sclerosis As A Neuronal Disease written by Stephen Waxman and published by Elsevier. This book was released on 2005-05-27 with total page 495 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book examines the role of neurons in multiple sclerosis (MS) and the changes that occur in neurons as a result of MS. It places MS in a new and important perspective that not only explains the basis for symptom production, remission, and progress in MS, but also promises to open up new therapeutic possibilities.* Brings together the latest information from clinical, pathological, imaging, molecular, and pharmacological realms to explore the neurobiology of Multiple Sclerosis* Places MS in a new and important perspective that promises to open up new therapeutic avenues* Superbly illustrated and referenced