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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...

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Autores principales: Wong, Joanna H., Halliday, Glenda M., Kim, Woojin Scott
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society for Brain and Neural Science 2014
Materias:
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.
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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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