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ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease
Amyotrophic Lateral Sclerosis (ALS) is being redefined as a distal axonopathy, in that many molecular changes influencing motor neuron degeneration occur at the neuromuscular junction (NMJ) at very early stages of the disease prior to symptom onset. A huge variety of genetic and environmental causes...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132373/ https://www.ncbi.nlm.nih.gov/pubmed/25177267 http://dx.doi.org/10.3389/fnins.2014.00252 |
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author | Moloney, Elizabeth B. de Winter, Fred Verhaagen, Joost |
author_facet | Moloney, Elizabeth B. de Winter, Fred Verhaagen, Joost |
author_sort | Moloney, Elizabeth B. |
collection | PubMed |
description | Amyotrophic Lateral Sclerosis (ALS) is being redefined as a distal axonopathy, in that many molecular changes influencing motor neuron degeneration occur at the neuromuscular junction (NMJ) at very early stages of the disease prior to symptom onset. A huge variety of genetic and environmental causes have been associated with ALS, and interestingly, although the cause of the disease can differ, both sporadic and familial forms of ALS show a remarkable similarity in terms of disease progression and clinical manifestation. The NMJ is a highly specialized synapse, allowing for controlled signaling between muscle and nerve necessary for skeletal muscle function. In this review we will evaluate the clinical, animal experimental and cellular/molecular evidence that supports the idea of ALS as a distal axonopathy. We will discuss the early molecular mechanisms that occur at the NMJ, which alter the functional abilities of the NMJ. Specifically, we focus on the role of axon guidance molecules on the stability of the cytoskeleton and how these molecules may directly influence the cells of the NMJ in a way that may initiate or facilitate the dismantling of the neuromuscular synapse in the presymptomatic stages of ALS. |
format | Online Article Text |
id | pubmed-4132373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-41323732014-08-29 ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease Moloney, Elizabeth B. de Winter, Fred Verhaagen, Joost Front Neurosci Psychiatry Amyotrophic Lateral Sclerosis (ALS) is being redefined as a distal axonopathy, in that many molecular changes influencing motor neuron degeneration occur at the neuromuscular junction (NMJ) at very early stages of the disease prior to symptom onset. A huge variety of genetic and environmental causes have been associated with ALS, and interestingly, although the cause of the disease can differ, both sporadic and familial forms of ALS show a remarkable similarity in terms of disease progression and clinical manifestation. The NMJ is a highly specialized synapse, allowing for controlled signaling between muscle and nerve necessary for skeletal muscle function. In this review we will evaluate the clinical, animal experimental and cellular/molecular evidence that supports the idea of ALS as a distal axonopathy. We will discuss the early molecular mechanisms that occur at the NMJ, which alter the functional abilities of the NMJ. Specifically, we focus on the role of axon guidance molecules on the stability of the cytoskeleton and how these molecules may directly influence the cells of the NMJ in a way that may initiate or facilitate the dismantling of the neuromuscular synapse in the presymptomatic stages of ALS. Frontiers Media S.A. 2014-08-14 /pmc/articles/PMC4132373/ /pubmed/25177267 http://dx.doi.org/10.3389/fnins.2014.00252 Text en Copyright © 2014 Moloney, de Winter and Verhaagen. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Moloney, Elizabeth B. de Winter, Fred Verhaagen, Joost ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease |
title | ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease |
title_full | ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease |
title_fullStr | ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease |
title_full_unstemmed | ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease |
title_short | ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease |
title_sort | als as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132373/ https://www.ncbi.nlm.nih.gov/pubmed/25177267 http://dx.doi.org/10.3389/fnins.2014.00252 |
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