| 1. |
- Ochala, Julien
(författare)
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Ca2+ sensitizers : An emerging class of agents for counterbalancing weakness in skeletal muscle diseases?
- 2010
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Ingår i: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966 .- 1873-2364. ; 20:2, s. 98-101
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Forskningsöversikt (refereegranskat)abstract
- Ca(2+) ions are key regulators of skeletal muscle contraction. By binding to contractile proteins, they initiate a cascade of molecular events leading to cross-bridge formation and ultimately, muscle shortening and force production. The ability of contractile proteins to respond to Ca(2+) attachment, also known as Ca(2+) sensitivity, is often compromised in acquired and congenital skeletal muscle disorders. It constitutes, undoubtedly, a major physiological cause of weakness for patients. In this review, we discuss recent studies giving strong molecular and cellular evidence that pharmacological modulators of some of the contractile proteins, also termed Ca(2+) sensitizers, are efficient agents to improve Ca(2+) sensitivity and function in diseased skeletal muscle cells. In fact, they compensate for the impaired contractile proteins response to Ca(2+) binding. Currently, such Ca(2+) sensitizing compounds are successfully used for reducing problems in cardiac disorders. Therefore, in the future, under certain conditions, these agents may represent an emerging class of agents to enhance the quality of life of patients suffering from skeletal muscle weakness.
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| 2. |
- Oldfors, Anders, 1951
(författare)
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Hereditary myosin myopathies
- 2007
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Ingår i: Neuromuscul Disord. - : Elsevier BV. ; 17:5, s. 355-67
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Forskningsöversikt (refereegranskat)abstract
- Hereditary myosin myopathies have emerged as a new group of muscle diseases with highly variable clinical features and onset during fetal development, childhood or adulthood. They are caused by mutations in skeletal muscle myosin heavy chain (MyHC) genes. Mutations have been reported in two of the three MyHC isoforms expressed in adult limb skeletal muscle: type I (slow/beta-cardiac MyHC; MYH7) and type IIa (MYH2). The majority of more than 200 dominant missense mutations in MYH7 are associated with hypertrophic/dilated cardiomyopathy without signs or symptoms of skeletal myopathy. Several mutations in two different parts of the slow/beta-cardiac MyHC rod region are associated with two distinct skeletal myopathies without cardiomyopathy: Laing early onset distal myopathy and myosin storage myopathy (MSM). However, early onset distal myopathy and MSM caused by MYH7 mutations may also occur together with cardiomyopathy. MSM affects proximal or scapuloperoneal muscles whereas Laing distal myopathy primarily affects the dorsiflexor muscles of the toes and ankles. MSM is morphologically characterized by subsarcolemmal accumulation of myosin in type 1 fibers, whereas Laing distal myopathy is associated with variable and unspecific muscle pathology, frequently with hypotrophic type 1 muscle fibers. A myopathy associated with a specific mutation in MYH2 is associated with congenital joint contractures and external ophthalmoplegia. The disease is mild in childhood but may be progressive in adulthood, with proximal muscle weakness affecting ambulation. Mutations in embryonic MyHC (MYH3) and perinatal MyHC (MYH8), which are myosin isoforms expressed during muscle development, are associated with distal arthrogryposis syndromes with no or minor muscle weakness. Clinical findings, muscle morphology and molecular genetics in hereditary myosin myopathies are summarized in this review.
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| 3. |
- Tajsharghi, Homa, 1968, et al.
(författare)
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Myopathies associated with beta-tropomyosin mutations
- 2012
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Ingår i: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966. ; 22:11, s. 923-933
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Forskningsöversikt (refereegranskat)abstract
- Mutations in TPM2, encoding beta-tropomyosin, have recently been found to cause a range of muscle disorders. We review the clinical and morphological expression of the previously reported mutations illustrating the heterogeneity of beta-tropomyosin-associated diseases and describe an additional case with a novel mutation. The manifestations of mutations in TPM2 include non-specific congenital myopathy with type 1 fibre predominance, nemaline myopathy, cap disease and distal arthrogryposis. In addition, Escobar syndrome with nemaline myopathy is a manifestation of homozygous truncating beta-tropomyosin mutation. Cap disease appears to be the most common morphological manifestation. A coarse intermyofibrillar network and jagged Z line:; are additional frequent changes. The dominant beta-tropomyosin mutations manifest either as congenital myopathy or distal arthrogryposis. The various congenital myopathies are usually associated with moderate muscle weakness and no congenital joint contractures. The distal arthrogryposis syndromes associated with TPM2 mutations include the less severe forms, with congenital contractures mainly of the hands and feet and mild or no muscle weakness. The dominant TPM2 mutations include amino acid deletions/insertions and missense mutations. There is no clear relation between the type of mutations or the localisation of the mutated residue in the beta-tropomyosin molecule and the clinical and morphological phenotype. (C) 2012 Elsevier B.V. All rights reserved.
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| 4. |
- Tajsharghi, Homa, et al.
(författare)
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Myopathies associated with β-tropomyosin mutations
- 2012
-
Ingår i: Neuromuscular Disorders. - : Elsevier. - 0960-8966 .- 1873-2364. ; 22:11, s. 923-933
-
Forskningsöversikt (refereegranskat)abstract
- Mutations in TPM2, encoding β-tropomyosin, have recently been found to cause a range of muscle disorders. We review the clinical and morphological expression of the previously reported mutations illustrating the heterogeneity of β-tropomyosin-associated diseases and describe an additional case with a novel mutation. The manifestations of mutations in TPM2 include non-specific congenital myopathy with type 1 fibre predominance, nemaline myopathy, cap disease and distal arthrogryposis. In addition, Escobar syndrome with nemaline myopathy is a manifestation of homozygous truncating β-tropomyosin mutation. Cap disease appears to be the most common morphological manifestation. A coarse intermyofibrillar network and jagged Z lines are additional frequent changes. The dominant β-tropomyosin mutations manifest either as congenital myopathy or distal arthrogryposis. The various congenital myopathies are usually associated with moderate muscle weakness and no congenital joint contractures. The distal arthrogryposis syndromes associated with TPM2 mutations include the less severe forms, with congenital contractures mainly of the hands and feet and mild or no muscle weakness. The dominant TPM2 mutations include amino acid deletions/insertions and missense mutations. There is no clear relation between the type of mutations or the localisation of the mutated residue in the β-tropomyosin molecule and the clinical and morphological phenotype.
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