Axon Degeneration
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Axon Degeneration
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Author : Elisabetta Babetto
language : en
Publisher: Humana
Release Date : 2020-06-11
Axon Degeneration written by Elisabetta Babetto and has been published by Humana this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-06-11 with Science categories.
This book is a collection of classical as well as innovative methods used to investigate axon degeneration with a particular focus on addressing the common challenges encountered while performing these procedures. Particular attention is devoted to the study of axon loss in several model organisms, as each poses unique challenges and provides powerful advantages. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Axon Degeneration: Methods and Protocols is an ideal guide for facilitating the application and further development of these protocols, which will help the scientific community tackle important questions regarding axon degeneration. Chapters 2, 3, and 20 are available Open Access under a Creative Commons Attribution 4.0 International License via link.springer.com.
What Is The Molecular Mechanism Of Axon Degeneration
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Author : Jack Tzu-Chieh Wang
language : en
Publisher:
Release Date : 2014
What Is The Molecular Mechanism Of Axon Degeneration written by Jack Tzu-Chieh Wang and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.
Axonal degeneration is a pivotal pathological event in most CNS and PNS diseases, but the molecular mechanisms that control this process remain unclear. Expression of the Wallerian degeneration slow (WldS) transgene robustly delays axon degeneration in various injury models and attenuate disease progression in many neurodegenerative conditions, indicating a common mechanism of axonal self-destruction in traumatic injuries and chronic degenerative events. In this thesis, I examined the mechanism of WldS axon protection as a window to understand the molecular events that orchestrate this axonal self-destruction program. In the first part of my thesis, I demonstrated that continuous, local WldS enzymatic activity in the axon, independent of nuclear gene transcription, is required to confer axonal protection. Furthermore, I showed that injured axons are not immediately committed to degeneration, but rather there is a critical period of 4-5hrs after injury in which the course of degeneration can be reversed. The presence of this latency period before the injured axons irreversibly commit to degeneration suggest that axonal degeneration can be attenuated or halted altogether even long after an injury has occurred. In the second part of the thesis, I investigated the signaling events and mechanisms that are responsible for translating WldS activity into axonal protection. I showed that NAD+, a metabolite of WldS enzymatic activity and a known redox cofactor in the mitochondria, is sufficient and specific to confer WldS-like axon protection. However, WldS axonal protection does not require the axonal mitochondria or involve changes in the bioenergy levels of the axon. I further demonstrated that independently increasing expression of Ca2+ buffering proteins in subcellular compartments is sufficient to delay axonal degeneration, suggesting that enhancement of Ca2+ buffering capacity in axonal subcellular compartments may be one mechanism by which WldS activity or NAD+ confers axonal protection. Finally, comparing the metabolomics profile of WT vs. WldS neurons reveals candidates in mediating NAD+ dependent regulation of intra-axonal Ca2+, and presents potential therapeutic targets to delay axon degeneration. In the third part of my thesis, I investigated the relationship between developmental axonal outgrowth, synaptic targeting and axon regeneration. Using retinal ganglion cells (RGCs) as a model system, I profiled the developmental expression of RGC genes from early embryonic to early postnatal development, a period that was previously shown to trigger a genetic switch to significantly slow the axonal growth rate. In particular, I showed that cyp1b1, a gene implicated in congenital glaucoma, is a potent source of retinoic acid during early RGC development and enhances RGC survival by sustaining retinoic acid production. In addition, several other genes from the expression profiling have been found by others to be involved in axonal regeneration after injury. Together, the findings provide a rich database for understanding the molecular signatures that control the development of retinal ganglion cells, and help uncover genetic factors that regulate axonal growth, targeting and regeneration.
Axonopathy In Neurodegenerative Disease
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Author : Samuel D. Crish
language : en
Publisher: Frontiers Media SA
Release Date : 2019-02-05
Axonopathy In Neurodegenerative Disease written by Samuel D. Crish and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-02-05 with categories.
Axons are the major output processes of neurons, responsible for transmitting information to other neurons and tissues throughout the body. The 150,000+ kilometers of axons make up half of the brain's volume and require a large amount of energy. Normal axon function is the product of a massive number of intra- and extra-cellular mechanisms working in concert. Perhaps not surprisingly, the axon is a site of vulnerability during normal aging and in disease states, although this has only been recently appreciated. Axonopathy, broadly defined as functional or structural defects in the axon or its terminal, is common across a wide range of neurodegenerative conditions, including amyotrophic lateral sclerosis, Huntington’s, Parkinson’s, and Alzheimer’s diseases, glaucoma, and as a result of neurotoxin exposure or drug treatment. This Research Topic assembles a series of original research papers, reviews, and commentaries that will illustrate both the commonalities and important differences across neurodegenerative disorders. Though this collection cannot address all aspects of this topic, it is our hope that these manuscripts will educate other scientists and inspire new investigations into axon dysfunction and degeneration.
Electron Microscopy Of Axon Degeneration A Valuable Tool In Experimental Neuroanatomy
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Author : J.F. Alksne
language : en
Publisher: Springer
Release Date : 2013-11-11
Electron Microscopy Of Axon Degeneration A Valuable Tool In Experimental Neuroanatomy written by J.F. Alksne and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-11-11 with Medical categories.
Experimental methods for the mapping of nervous pathways are based partlyon the study of retrograde processes in the perikaryon, partlyon the demonstration of degenerative processes along the peripheral part of a transected axon. For this purpose, the Marchi method by which a selective staining of degenerating myelin is obtained has been extensively used. However, when this method is used the non-myelinated terminals of the transected axons are not stained. The introduction, about two decades ago, of silver impregnation as a means of tracing degenerating axons (especially the Glees and Nauta methods) by which also terminal boutons can be demonstrated, led therefore to revolutionary progress in the investigation of interneuronal connections. Notwithstanding, there are weH known difficulties involved in this kind of research. The capriciousness of the silver methods not seldom results in failure of impregnation with loss of valuable experimental animals. But even when well impregnated sections are used, other fundamental difficulties exist. One of the major problems is to prove beyond doubt that the impregnated structures are degenerating boutons and not merely fragments of non-terminal fibres passing the area under examination. Furthermore, only on occasion will silver impregnation permit one to accurately define the specific part of the receiving neuron on which the impregnated fibres end, i. e. , whether the bouton makes contact with soma, dendrite or spine.
Mechanisms Of Axon Degeneration And Its Blockade
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Author : Bogdan Karl Beirowski
language : en
Publisher:
Release Date : 2010
Mechanisms Of Axon Degeneration And Its Blockade written by Bogdan Karl Beirowski and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Electron Microscopy Of Axon Degeneration
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Author : J. F. Alksne
language : en
Publisher:
Release Date : 2014-01-15
Electron Microscopy Of Axon Degeneration written by J. F. Alksne and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-01-15 with categories.
Axon Degeneration Mechanisms In Alzheimer S Disease And Injury
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Author : Elisabetta Babetto
language : en
Publisher:
Release Date : 2011
Axon Degeneration Mechanisms In Alzheimer S Disease And Injury written by Elisabetta Babetto and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.
In Vivo Modelling Of Human Axon Degeneration
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Author : Mariarosa Tortora
language : en
Publisher:
Release Date : 2021
In Vivo Modelling Of Human Axon Degeneration written by Mariarosa Tortora and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with categories.
Electron Microscopy Of Axon Degeneration
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Author :
language : en
Publisher:
Release Date : 1966
Electron Microscopy Of Axon Degeneration written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1966 with categories.
Defining The Role Of Mapk Signaling In The Axonal Degeneration Pathway
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Author : Lauren Walker
language : en
Publisher:
Release Date : 2016
Defining The Role Of Mapk Signaling In The Axonal Degeneration Pathway written by Lauren Walker and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with Electronic dissertations categories.
Axons are neuronal projections that can extend for up to a meter to wire the nervous system over large distances. The incredible length of an axon makes it vulnerable to both injury and disease. Axonal integrity is actively regulated by the neuron and is controlled by a tight balance of pro-degenerative and pro-survival factors. NMNAT2, a NAD+-synthesizing enzyme, is a labile axon survival factor that is synthesized in the cell body and transported into the distal axon. NMNAT2 functions as a rheostat within the axon, such that when levels fall below a critical threshold, axon degeneration factors are activated. Axon degeneration is promoted by signaling from a mitogen-activated protein kinase (MAPK) cascade as well as the central regulator of axon degeneration, SARM1. While manipulating pro-degenerative and pro-survival factors can influence the progression of axon degeneration, a molecular pathway to unite these factors was unknown. Here, I demonstrate that MAPKs function upstream of SARM1 by dampening levels of axonal survival factors NMNAT2 and SCG10, a microtubule-binding protein. After axon injury, blocked axonal transport coupled with ongoing MAPK-dependent degradation causes depletion of NMNAT2 and subsequent activation of SARM1 and axon destruction. Importantly, these findings place major components of the axonal degeneration program into a linear molecular pathway and reveal drug targets that may be therapeutically beneficial.