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Myosinopathies: pathology and mechanisms
The myosin heavy chain (MyHC) is the molecular motor of muscle and forms the backbone of the sarcomere thick filaments. Different MyHC isoforms are of importance for the physiological properties of different muscle fiber types. Hereditary myosin myopathies have emerged as an important group of disea...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer-Verlag
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535372/ https://www.ncbi.nlm.nih.gov/pubmed/22918376 http://dx.doi.org/10.1007/s00401-012-1024-2 |
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author | Tajsharghi, Homa Oldfors, Anders |
author_facet | Tajsharghi, Homa Oldfors, Anders |
author_sort | Tajsharghi, Homa |
collection | PubMed |
description | The myosin heavy chain (MyHC) is the molecular motor of muscle and forms the backbone of the sarcomere thick filaments. Different MyHC isoforms are of importance for the physiological properties of different muscle fiber types. Hereditary myosin myopathies have emerged as an important group of diseases with variable clinical and morphological expression depending on the mutated isoform and type and location of the mutation. Dominant mutations in developmental MyHC isoform genes (MYH3 and MYH8) are associated with distal arthrogryposis syndromes. Dominant or recessive mutations affecting the type IIa MyHC (MYH2) are associated with early-onset myopathies with variable muscle weakness and ophthalmoplegia as a consistent finding. Myopathies with scapuloperoneal, distal or limb-girdle muscle weakness including entities, such as myosin storage myopathy and Laing distal myopathy are the result of usually dominant mutations in the gene for slow/β cardiac MyHC (MYH7). Protein aggregation is part of the features in some of these myopathies. In myosin storage myopathy protein aggregates are formed by accumulation of myosin beneath the sarcolemma and between myofibrils. In vitro studies on the effects of different mutations associated with myosin storage myopathy and Laing distal myopathy indicate altered biochemical and biophysical properties of the light meromyosin, which is essential for thick filament assembly. Protein aggregates in the form of tubulofilamentous inclusions in association with vacuolated muscle fibers are present at late stage of dominant myosin IIa myopathy and sometimes in Laing distal myopathy. These protein aggregates exhibit features indicating defective degradation of misfolded proteins. In addition to protein aggregation and muscle fiber degeneration some of the myosin mutations cause functional impairment of the molecular motor adding to the pathogenesis of myosinopathies. |
format | Online Article Text |
id | pubmed-3535372 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-35353722013-01-04 Myosinopathies: pathology and mechanisms Tajsharghi, Homa Oldfors, Anders Acta Neuropathol Review The myosin heavy chain (MyHC) is the molecular motor of muscle and forms the backbone of the sarcomere thick filaments. Different MyHC isoforms are of importance for the physiological properties of different muscle fiber types. Hereditary myosin myopathies have emerged as an important group of diseases with variable clinical and morphological expression depending on the mutated isoform and type and location of the mutation. Dominant mutations in developmental MyHC isoform genes (MYH3 and MYH8) are associated with distal arthrogryposis syndromes. Dominant or recessive mutations affecting the type IIa MyHC (MYH2) are associated with early-onset myopathies with variable muscle weakness and ophthalmoplegia as a consistent finding. Myopathies with scapuloperoneal, distal or limb-girdle muscle weakness including entities, such as myosin storage myopathy and Laing distal myopathy are the result of usually dominant mutations in the gene for slow/β cardiac MyHC (MYH7). Protein aggregation is part of the features in some of these myopathies. In myosin storage myopathy protein aggregates are formed by accumulation of myosin beneath the sarcolemma and between myofibrils. In vitro studies on the effects of different mutations associated with myosin storage myopathy and Laing distal myopathy indicate altered biochemical and biophysical properties of the light meromyosin, which is essential for thick filament assembly. Protein aggregates in the form of tubulofilamentous inclusions in association with vacuolated muscle fibers are present at late stage of dominant myosin IIa myopathy and sometimes in Laing distal myopathy. These protein aggregates exhibit features indicating defective degradation of misfolded proteins. In addition to protein aggregation and muscle fiber degeneration some of the myosin mutations cause functional impairment of the molecular motor adding to the pathogenesis of myosinopathies. Springer-Verlag 2012-08-05 2013 /pmc/articles/PMC3535372/ /pubmed/22918376 http://dx.doi.org/10.1007/s00401-012-1024-2 Text en © The Author(s) 2012 https://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Review Tajsharghi, Homa Oldfors, Anders Myosinopathies: pathology and mechanisms |
title | Myosinopathies: pathology and mechanisms |
title_full | Myosinopathies: pathology and mechanisms |
title_fullStr | Myosinopathies: pathology and mechanisms |
title_full_unstemmed | Myosinopathies: pathology and mechanisms |
title_short | Myosinopathies: pathology and mechanisms |
title_sort | myosinopathies: pathology and mechanisms |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535372/ https://www.ncbi.nlm.nih.gov/pubmed/22918376 http://dx.doi.org/10.1007/s00401-012-1024-2 |
work_keys_str_mv | AT tajsharghihoma myosinopathiespathologyandmechanisms AT oldforsanders myosinopathiespathologyandmechanisms |