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 Neuroglia Molecular Mechanisms in Psychiatric Disorders written by Caterina Scuderi and published by Frontiers Media SA. This book was released on 2019-01-21 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuropsychiatric disorders have long been considered as specific dysfunctions of neuronal functions. Studies of the recent decade, however, have challenged this simplistic view, highlighting the important role played by neuroglial cells in the onset and/or progression of neuropsychiatric diseases. In the central nervous system (CNS) non-excitable neuroglia are represented by cells of ectodermal origin (astrocytes, mainly responsible for CNS homeostasis and oligodendrocytes that provide myelination and support for axons) and mesodermal origin (microglial cells that are scions of foetal macrophages entering the neural tube early in development; these cells provide for CNS defence and contribute to shaping neuronal networks). Pathological changes of neuroglia are complex; these changes are classified into reactive gliosis (astrogliosis, activation of microglia and hypertrophy of oligodendroglial precursors), gliodegeneration with loss of function and glial pathological remodelling. Combination of these processes defines the evolution of neurological diseases in general and neuropsychiatric disorders in particular. In this research topic we addressed the contribution of neuroglia to major neuropsychiatric pathologies including major depression, schizophrenia, and addictive disorders.

Download or read book Neurodegenerative Diseases written by Nagehan Ersoy Tunalı and published by BoD – Books on Demand. This book was released on 2021-01-20 with total page 180 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurodegenerative diseases represent a very large group of heterogeneous disorders affecting specific subtypes of neurons in the brain. This book contributes insight both to the awareness of the brain and its neurodegenerative states. The chapters present current knowledge regarding genetics, molecular mechanisms, and new therapeutic strategies against neurodegenerative disorders. The book is intended to serve as a source to aid clinicians and researchers in the field, and also life science readers to increase their understanding and awareness of the clinical correlations, genetic aspects, neuropathological findings, and current therapeutic interventions in neurodegenerative diseases. I believe that this book will enlighten the curiosity for neurodegeneration and also encourage researchers to work on potentially effective molecular therapies for still mysterious neurodegenerative disorders.

Download or read book Molecular Mechanisms of Pathogenesis of Central Nervous System Disorders written by Amico Bignami and published by . This book was released on 1985 with total page 157 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Peripheral Nerve Disorders written by Grahame J. Kidd and published by Elsevier Inc. Chapters. This book was released on 2013-08-17 with total page 63 pages. Available in PDF, EPUB and Kindle. Book excerpt: The fundamental roles of Schwann cells during peripheral nerve formation and regeneration have been recognized for more than 100 years, but the cellular and molecular mechanisms that integrate Schwann cell and axonal functions continue to be elucidated. Derived from the embryonic neural crest, Schwann cells differentiate into myelinating cells or bundle multiple unmyelinated axons into Remak fibers. Axons dictate which differentiation path Schwann cells follow, and recent studies have established that axonal neuregulin1 signaling via ErbB2/B3 receptors on Schwann cells is essential for Schwann cell myelination. Extracellular matrix production and interactions mediated by specific integrin and dystroglycan complexes are also critical requisites for Schwann cell–axon interactions. Myelination entails expansion and specialization of the Schwann cell plasma membrane over millimeter distances. Many of the myelin-specific proteins have been identified, and transgenic manipulation of myelin genes have provided novel insights into myelin protein function, including maintenance of axonal integrity and survival. Cellular events that facilitate myelination, including microtubule-based protein and mRNA targeting, and actin based locomotion, have also begun to be understood. Arguably, the most remarkable facet of Schwann cell biology, however, is their vigorous response to axonal damage. Degradation of myelin, dedifferentiation, division, production of axonotrophic factors, and remyelination all underpin the substantial regenerative capacity of the Schwann cells and peripheral nerves. Many of these properties are not shared by CNS fibers, which are myelinated by oligodendrocytes. Dissecting the molecular mechanisms responsible for the complex biology of Schwann cells continues to have practical benefits in identifying novel therapeutic targets not only for Schwann cell-specific diseases but other disorders in which axons degenerate.

Download or read book Mechanisms of Myelination It s All about the Matrix written by Sarah Degenova Ackerman and published by . This book was released on 2016 with total page 293 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myelin, the lipid-rich sheath that insulates axons to facilitate rapid conduction of action potentials, is generated by specialized glial cells -- oligodendrocytes (OLs) in the central nervous system (CNS) and Schwann cells (SCs) in the peripheral nervous system (PNS). The importance of myelin is underscored by the devastating symptoms experienced by patients who suffer from demyelinating diseases of the PNS (e.g., Charcot-Marie-Tooth disease) and CNS (e.g., multiple sclerosis, MS). The molecular mechanisms governing myelination are not fully understood, yet several studies implicate extracellular matrix (ECM) proteins and their receptors as important regulators of these processes (reviewed in Chapter 1 of this thesis). In my thesis work, I used both forward and reverse genetics to define two new regulators of myelination with links to the ECM: GPR56 and ADAMTS9. GPR56 belongs to a specialized class of G protein-coupled receptors (GPCRs) called the adhesion GPCRs (aGCPRs). aGPCRs mediate both cell-cell and cell-matrix interactions, and thus could play a role in myelinating glial cells. I used zebrafish and mouse models to define the function of GPR56 in both OL and SC development and myelination. First, I explore the function of Gpr56 in the CNS in zebrafish and show that gpr56 is robustly expressed in early stages of OL development. In addition, I demonstrate that impaired Gpr56 function results in a significant reduction of OL number and of myelination due to decreased proliferation of OL precursor cells, and that these functions of Gpr56 are mediated via interactions with G[alpha]12/13 proteins and RhoA activation (Ackerman et al. 2015, Nat Commun; Chapter 2 of this thesis). In contrast, diminished GPR56 function in the PNS of zebrafish and mouse mutants does not result in hypomyelination. Instead, loss of Gpr56 causes defects in axon-SC interactions during development, myelin structural abnormalities, and impaired myelin maintenance. Importantly, these developmental defects result in axon degeneration and progressive neuropathy in adult Gpr56 mutants (Ackerman et al., in revision; Chapter 3 of this thesis). As mutations in GPR56 in humans cause neurological disorders that can present with PNS pathology, my work defines Gpr56 as a novel, clinically relevant regulator of nervous system health. In a separate yet complimentary line of work, I conducted a large scale forward genetic screen in zebrafish in collaboration with members of the Monk and Solnica-Krezel laboratories and identified the secreted matrix metalloprotease ADAMTS9 as a critical new regulator of OL myelination. ADAMTS9 normally functions to cleave chondroitin sulfate proteoglycans (CSPGs) in the ECM, and accumulation of CSPGs is a major cause of failed axon regrowth and remyelination after CNS injury and in demyelinating plaques of MS brains. Excitingly, I find that myelin is lost in adamts9 zebrafish mutants concurrently with engulfment of OL lineage cells (including mature, myelinating OLs) by phagocytic immune cells, and that these phenotypes can be ameliorated upon removal of CSPGs from the ECM (Ackerman et al., in preparation; Chapter 4 of this thesis). MS is a complex, autoimmune disease in which the immune system attacks the OL myelin sheath, and the cause of this attack is unknown. Thus, the identification of ADAMTS9 as a critical regulator of OL-immune cell interactions represents a major advancement in our understanding of CNS demyelination, and may present a new therapeutic target for MS. In sum, my thesis work defined the roles of two previously unappreciated regulators of myelination, GPR56 and ADAMTS9, and further emphasized the importance of the extracellular matrix in modulating the development of myelinating glial cells.

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 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 Mechanisms Underlying the CNS Myelination written by Nicolas Snaidero and published by . This book was released on 2014 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Central nervous system myelin is a multilayered membrane sheath generated by oligodendrocytes for rapid axonal electrical impulse propagation. Both light and electron microscopy have been used to describe morphological features of the myelin sheath. However, the underlying mechanisms of myelin wrapping are still unclear and remain under debate. To investigate the morphology of the CNS myelin sheath during its formation we made use of multiple imaging techniques such as focus ion beam milling coupled to scanning electron microscopy, live imaging, transmission electron microscopy, cryo-immuno ...

Download or read book Brain Neurotrauma written by Firas H. Kobeissy and published by CRC Press. This book was released on 2015-02-25 with total page 718 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the contribution from more than one hundred CNS neurotrauma experts, this book provides a comprehensive and up-to-date account on the latest developments in the area of neurotrauma including biomarker studies, experimental models, diagnostic methods, and neurotherapeutic intervention strategies in brain injury research. It discusses neurotrauma mechanisms, biomarker discovery, and neurocognitive and neurobehavioral deficits. Also included are medical interventions and recent neurotherapeutics used in the area of brain injury that have been translated to the area of rehabilitation research. In addition, a section is devoted to models of milder CNS injury, including sports injuries.

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 Molecular Mechanisms of BDNF Signalling in Central Nervous System Myelination written by Haley Moss Peckham and published by . This book was released on 2016 with total page 288 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 Myelin Biology and Disorders written by Robert A. Lazzarini and published by . This book was released on 2004 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

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 Essential Concepts in Molecular Pathology written by William B. Coleman and published by Academic Press. This book was released on 2019-11-23 with total page 636 pages. Available in PDF, EPUB and Kindle. Book excerpt: Essential Concepts in Molecular Pathology, Second Edition, offers an introduction to molecular genetics and the "molecular" aspects of human disease. The book illustrates how pathologists harness their understanding of these entities to develop new diagnostics and treatments for various human diseases. This new edition offers pathology, genetics residents, and molecular pathology fellows an advanced understanding of the molecular mechanisms of disease that goes beyond what they learned in medical and graduate school. By bridging molecular concepts of pathogenesis to the clinical expression of disease in cell, tissue and organ, this fully updated, introductory reference provides the background necessary for an understanding of today's advances in pathology and medicine. - Explains the practice of "molecular medicine" and the translational aspects of molecular pathology, including molecular diagnostics, molecular assessment and personalized medicine - Orients non-pathologists on what pathologists look for and how they interpret their observational findings based on histopathology - Provides the reader with what is missing from most targeted introductions to pathology—the cell biology behind pathophysiology