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Exploring Myelin Dysfunction in Multiple System Atrophy
Multiple system atrophy (MSA) is a rare, yet fatal neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. MSA impacts on the autonomic nervous system affecting blood pressure, heart rate and bladder function, and the motor sys...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Korean Society for Brain and Neural Science
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276804/ https://www.ncbi.nlm.nih.gov/pubmed/25548533 http://dx.doi.org/10.5607/en.2014.23.4.337 |
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author | Wong, Joanna H. Halliday, Glenda M. Kim, Woojin Scott |
author_facet | Wong, Joanna H. Halliday, Glenda M. Kim, Woojin Scott |
author_sort | Wong, Joanna H. |
collection | PubMed |
description | Multiple system atrophy (MSA) is a rare, yet fatal neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. MSA impacts on the autonomic nervous system affecting blood pressure, heart rate and bladder function, and the motor system affecting balance and muscle movement. The cause of MSA is unknown, no definitive risk factors have been identified, and there is no cure or effective treatment. The definitive pathology of MSA is the presence of α-synuclein aggregates in the brain and therefore MSA is classified as an α-synucleinopathy, together with Parkinson's disease and dementia with Lewy bodies. Although the molecular mechanisms of misfolding, fibrillation and aggregation of α-synuclein partly overlap with other α-synucleinopathies, the pathological pathway of MSA is unique in that the principal site for α-synuclein deposition is in the oligodendrocytes rather than the neurons. The sequence of pathological events of MSA is now recognized as abnormal protein redistributions in oligodendrocytes first, followed by myelin dysfunction and then neurodegeneration. Oligodendrocytes are responsible for the production and maintenance of myelin, the specialized lipid membrane that encases the axons of all neurons in the brain. Myelin is composed of lipids and two prominent proteins, myelin basic protein and proteolipid protein. In vitro studies suggest that aberration in protein distribution and lipid transport may lead to myelin dysfunction in MSA. The purpose of this perspective is to bring together available evidence to explore the potential role of α-synuclein, myelin protein dysfunction, lipid dyshomeostasis and ABCA8 in MSA pathogenesis. |
format | Online Article Text |
id | pubmed-4276804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Korean Society for Brain and Neural Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42768042014-12-29 Exploring Myelin Dysfunction in Multiple System Atrophy Wong, Joanna H. Halliday, Glenda M. Kim, Woojin Scott Exp Neurobiol Review Article Multiple system atrophy (MSA) is a rare, yet fatal neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. MSA impacts on the autonomic nervous system affecting blood pressure, heart rate and bladder function, and the motor system affecting balance and muscle movement. The cause of MSA is unknown, no definitive risk factors have been identified, and there is no cure or effective treatment. The definitive pathology of MSA is the presence of α-synuclein aggregates in the brain and therefore MSA is classified as an α-synucleinopathy, together with Parkinson's disease and dementia with Lewy bodies. Although the molecular mechanisms of misfolding, fibrillation and aggregation of α-synuclein partly overlap with other α-synucleinopathies, the pathological pathway of MSA is unique in that the principal site for α-synuclein deposition is in the oligodendrocytes rather than the neurons. The sequence of pathological events of MSA is now recognized as abnormal protein redistributions in oligodendrocytes first, followed by myelin dysfunction and then neurodegeneration. Oligodendrocytes are responsible for the production and maintenance of myelin, the specialized lipid membrane that encases the axons of all neurons in the brain. Myelin is composed of lipids and two prominent proteins, myelin basic protein and proteolipid protein. In vitro studies suggest that aberration in protein distribution and lipid transport may lead to myelin dysfunction in MSA. The purpose of this perspective is to bring together available evidence to explore the potential role of α-synuclein, myelin protein dysfunction, lipid dyshomeostasis and ABCA8 in MSA pathogenesis. The Korean Society for Brain and Neural Science 2014-12 2014-12-12 /pmc/articles/PMC4276804/ /pubmed/25548533 http://dx.doi.org/10.5607/en.2014.23.4.337 Text en Copyright © Experimental Neurobiology 2014. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Wong, Joanna H. Halliday, Glenda M. Kim, Woojin Scott Exploring Myelin Dysfunction in Multiple System Atrophy |
title | Exploring Myelin Dysfunction in Multiple System Atrophy |
title_full | Exploring Myelin Dysfunction in Multiple System Atrophy |
title_fullStr | Exploring Myelin Dysfunction in Multiple System Atrophy |
title_full_unstemmed | Exploring Myelin Dysfunction in Multiple System Atrophy |
title_short | Exploring Myelin Dysfunction in Multiple System Atrophy |
title_sort | exploring myelin dysfunction in multiple system atrophy |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276804/ https://www.ncbi.nlm.nih.gov/pubmed/25548533 http://dx.doi.org/10.5607/en.2014.23.4.337 |
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