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Desminopathies: pathology and mechanisms

The intermediate filament protein desmin is an essential component of the extra-sarcomeric cytoskeleton in muscle cells. This three-dimensional filamentous framework exerts central roles in the structural and functional alignment and anchorage of myofibrils, the positioning of cell organelles and si...

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Autores principales: Clemen, Christoph S., Herrmann, Harald, Strelkov, Sergei V., Schröder, Rolf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535371/
https://www.ncbi.nlm.nih.gov/pubmed/23143191
http://dx.doi.org/10.1007/s00401-012-1057-6
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author Clemen, Christoph S.
Herrmann, Harald
Strelkov, Sergei V.
Schröder, Rolf
author_facet Clemen, Christoph S.
Herrmann, Harald
Strelkov, Sergei V.
Schröder, Rolf
author_sort Clemen, Christoph S.
collection PubMed
description The intermediate filament protein desmin is an essential component of the extra-sarcomeric cytoskeleton in muscle cells. This three-dimensional filamentous framework exerts central roles in the structural and functional alignment and anchorage of myofibrils, the positioning of cell organelles and signaling events. Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant, autosomal recessive, and sporadic myopathies and/or cardiomyopathies with marked phenotypic variability. The disease onset ranges from childhood to late adulthood. The clinical course is progressive and no specific treatment is currently available for this severely disabling disease. The muscle pathology is characterized by desmin-positive protein aggregates and degenerative changes of the myofibrillar apparatus. The molecular pathophysiology of desminopathies is a complex, multilevel issue. In addition to direct effects on the formation and maintenance of the extra-sarcomeric intermediate filament network, mutant desmin affects essential protein interactions, cell signaling cascades, mitochondrial functions, and protein quality control mechanisms. This review summarizes the currently available data on the epidemiology, clinical phenotypes, myopathology, and genetics of desminopathies. In addition, this work provides an overview on the expression, filament formation processes, biomechanical properties, post-translational modifications, interaction partners, subcellular localization, and functions of wild-type and mutant desmin as well as desmin-related cell and animal models.
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spelling pubmed-35353712013-01-04 Desminopathies: pathology and mechanisms Clemen, Christoph S. Herrmann, Harald Strelkov, Sergei V. Schröder, Rolf Acta Neuropathol Review The intermediate filament protein desmin is an essential component of the extra-sarcomeric cytoskeleton in muscle cells. This three-dimensional filamentous framework exerts central roles in the structural and functional alignment and anchorage of myofibrils, the positioning of cell organelles and signaling events. Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant, autosomal recessive, and sporadic myopathies and/or cardiomyopathies with marked phenotypic variability. The disease onset ranges from childhood to late adulthood. The clinical course is progressive and no specific treatment is currently available for this severely disabling disease. The muscle pathology is characterized by desmin-positive protein aggregates and degenerative changes of the myofibrillar apparatus. The molecular pathophysiology of desminopathies is a complex, multilevel issue. In addition to direct effects on the formation and maintenance of the extra-sarcomeric intermediate filament network, mutant desmin affects essential protein interactions, cell signaling cascades, mitochondrial functions, and protein quality control mechanisms. This review summarizes the currently available data on the epidemiology, clinical phenotypes, myopathology, and genetics of desminopathies. In addition, this work provides an overview on the expression, filament formation processes, biomechanical properties, post-translational modifications, interaction partners, subcellular localization, and functions of wild-type and mutant desmin as well as desmin-related cell and animal models. Springer-Verlag 2012-11-11 2013 /pmc/articles/PMC3535371/ /pubmed/23143191 http://dx.doi.org/10.1007/s00401-012-1057-6 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
Clemen, Christoph S.
Herrmann, Harald
Strelkov, Sergei V.
Schröder, Rolf
Desminopathies: pathology and mechanisms
title Desminopathies: pathology and mechanisms
title_full Desminopathies: pathology and mechanisms
title_fullStr Desminopathies: pathology and mechanisms
title_full_unstemmed Desminopathies: pathology and mechanisms
title_short Desminopathies: pathology and mechanisms
title_sort desminopathies: pathology and mechanisms
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535371/
https://www.ncbi.nlm.nih.gov/pubmed/23143191
http://dx.doi.org/10.1007/s00401-012-1057-6
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