Investigation of Molecular and Cellular Mechanism of Myelin - Induced Axonal Degeneration PDF Download

Author: Asli Dedeagac
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Author: Stephen G. Waxman
Publisher:
ISBN: 0195082931
Category : Axons
Languages : en
Pages : 710

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Book Description
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.

Author: Jihyun Kim
Publisher:
ISBN:
Category : Myelin proteins
Languages : en
Pages : 166

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Book Description
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.

Author: James A. Radosevich
Publisher: John Wiley & Sons
ISBN: 1119432359
Category : Science
Languages : en
Pages : 768

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These volumes teach readers to think beyond apoptosis and describes all of the known processes that cells can undergo which result in cell death This two-volume source on how cells dies is the first, comprehensive collection to cover all of the known processes that cells undergo when they die. It is also the only one of its kind to compare these processes. It seeks to enlighten those in the field about these many processes and to stimulate their thinking at looking at these pathways when their research system does not show signs of activation of the classic apoptotic pathway. In addition, it links activities like the molecular biology of one process (eg. Necrosis) to another process (eg. apoptosis) and contrasts those that are close to each. Volume 1 of Apoptosis and Beyond: The Many Ways Cells Die begins with a general view of the cytoplasmic and nuclear features of apoptosis. It then goes on to offer chapters on targeting the cell death mechanism; microbial programmed cell death; autophagy; cell injury, adaptation, and necrosis; necroptosis; ferroptosis; anoikis; pyronecrosis; and more. Volume 2 covers such subjects as phenoptosis; pyroptosis; hematopoiesis and eryptosis; cyclophilin d-dependent necrosis; and the role of phospholipase in cell death. Covers all known processes that dying cells undergo Provides extensive coverage of a topic not fully covered before Offers chapters written by top researchers in the field Provides activities that link and contrast processes to each other Apoptosis and Beyond: The Many Ways Cells Die will appeal to students and researchers/clinicians in cell biology, molecular biology, oncology, and tumor biology.

Author: Jun Chen
Publisher: Springer Science & Business Media
ISBN: 1603271856
Category : Medical
Languages : en
Pages : 490

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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.

Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309072859
Category : Medical
Languages : en
Pages : 457

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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.

Author: Daniel Laskowitz
Publisher: CRC Press
ISBN: 1498766579
Category : Medical
Languages : en
Pages : 388

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Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the developme

Author: Illana Gozes
Publisher: Academic Press
ISBN: 0128037121
Category : Psychology
Languages : en
Pages : 344

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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

Author: Abel Lajtha
Publisher: Springer Science & Business Media
ISBN: 0387326707
Category : Medical
Languages : en
Pages : 332

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The nervous system is highly fragile, especially during aging, illness and trauma. This book addresses a small sampling of major constituents of neural function at the cellular and molecular level that play crucial roles in development and aging.

Author: M. Filippi
Publisher: Springer Science & Business Media
ISBN: 8847003911
Category : Medical
Languages : en
Pages : 233

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Written by world-renowned scientists, the volume provides a state-of-the-art on the most recent MRI techniques related to MS, and it is an indispensable tool for all those working in this field. The context in which this book exists is that there is an increasing perception that modern MR methodologies should be more extensively employed in clinical trials to derive innovative information.