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Molecular pathology of myofibrillar myopathies

Published online by Cambridge University Press:  03 September 2008

Isidre Ferrer  and
Montse Olivé
Isidre Ferrer*
Affiliation:
Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat, Spain. CIBERNED, Spain.
Montse Olivé
Affiliation:
Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat, Spain. CIBERNED, Spain.
*
*Corresponding author: Isidre Ferrer, Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Spain. Tel: +34 932607452; Fax: +34 932607503; E-mail: [email protected]
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Abstract

Myofibrillar myopathies (MFMs) are clinically and genetically heterogeneous muscle disorders that are defined morphologically by the presence of foci of myofibril dissolution, accumulation of myofibrillar degradation products, and ectopic expression of multiple proteins. MFMs are the paradigm of conformational protein diseases of the skeletal (and cardiac) muscles characterised by intracellular protein accumulation in muscle cells. Understanding of this group of disorders has advanced in recent years through the identification of causative mutations in various genes, most of which encode proteins of the sarcomeric Z-disc, including desmin, αB-crystallin, myotilin, ZASP and filamin C. This review focuses on the MFMs arising from defects in these proteins, summarising genetic and clinical features of the disorders and then discussing emerging understanding of the molecular pathogenic mechanisms leading to muscle fibre degeneration. Defective extralysosomal degradation of proteins is now recognised as an important element in this process. Several factors – including mutant proteins, a defective ubiquitin–proteasome system, aggresome formation, mutant ubiquitin, p62, oxidative stress and abnormal regulation of some transcription factors – are thought to participate in the cascade of events occurring in muscle fibres in MFMs.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 10 , October 2008 , e25
Copyright
Copyright © Cambridge University Press 2008

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References

References

1Nakano, S. et al. (1996) Myofibrillar myopathy with abnormal foci of desmin positivity. I. Light and electron miscroscopy analysis of 10 cases. J Neuropathol Exp Neurol 55, 549-562CrossRefGoogle Scholar
2De Bleecker, J.L., Engel, A.G. and Ertl, B. (1996) Myofibrillar myopathy with foci of desmin positivity. II. Immunocytochemical analysis reveals accumulation of multiple other proteins. J Neuropathol Exp Neurol 55, 563-577CrossRefGoogle ScholarPubMed
3Nakano, S. et al. (1997) Myofibrillar myopathy. III. Abnormal expression of cyclin-dependent kinases and nuclear proteins. J Neuropathol Exp Neurol 56, 850-856CrossRefGoogle ScholarPubMed
4Goebel, H.H. (1995) Desmin-related neuromuscular disorders. Muscle Nerve 18, 1306-1320CrossRefGoogle ScholarPubMed
5Goebel, H.H. and Fardeau, M. (2002) Desmin-protein surplus myopathies, 96th European Neuromuscular Centre (ENMC)-sponsored International Workshop held 14-16 September 2001, Naarden, The Netherlands. Neuromusc Disord 12, 687-692CrossRefGoogle ScholarPubMed
6Goebel, H.H. and Goldfarb, L. (2002) Desmin-related myopathies. In Structural and Molecular Basis of Skeletal Muscle Diseases (Karpati, K., ed.), pp. 70-73, ISN Neuropath Press, BaselGoogle Scholar
7Goldfarb, L.G. et al. (2004) Desmin myopathy. Brain 127, 723-734CrossRefGoogle ScholarPubMed
8Olivé, M. et al. (2004) Desmin-related myopathy: clinical, electrophysiological, radiological, neuropathological and genetic studies. J Neurol Sci 219, 125-137CrossRefGoogle ScholarPubMed
9Olivé, M. et al. (2003) Expression of intermediate filament protein synemin in myofibrillar myopathies and other muscle diseases. Acta Neuropathol 106, 1-7CrossRefGoogle ScholarPubMed
10Ferrer, I. et al. (2004) Proteasomal expression and activity, and induction of the immunoproteasome in myofibrilar myopathies and inclusion body myositis. J Neuropathol Exp Neurol 63, 484-498CrossRefGoogle Scholar
11Selcen, D., Ohno, K. and Engel, A.G. (2004) Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain 127, 439-451CrossRefGoogle ScholarPubMed
12Goldfarb, L.G. et al. (1998) Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet 19, 402-403CrossRefGoogle ScholarPubMed
13Muñoz-Mármol, A.M. et al. (1998) A dysfunctional desmin mutation in a patient with severe generalised myopathy. Proc Natl Acad Sci USA 95, 11312-11317CrossRefGoogle Scholar
14Dalakas, M.C. et al. (2000) Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N Engl J Med 342, 770-780CrossRefGoogle ScholarPubMed
15Vicart, P. et al. (1998) A missense mutation in the αB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 20, 92-95CrossRefGoogle ScholarPubMed
16Selcen, D. and Engel, A.G. (2004) Mutations in myotilin cause myofibrillar myopathy. Neurology 62, 1363-1371CrossRefGoogle ScholarPubMed
17Selcen, D. and Engel, A.G. (2005) Mutations in ZASP define a novel form of muscular dystrophy in humans. Ann Neurol 57, 269-276CrossRefGoogle ScholarPubMed
18Vorgerd, M. et al. (2005) A mutation in the dimerization domain of filamin causes a novel type of autosomal dominant myofibrillar myopathy. Am J Hum Genet 77, 297-304CrossRefGoogle ScholarPubMed
19Goebel, H.H. and Warlo, I. (2000) Gene-related protein surplus myopathies. Mol Genet Metab 71, 267-275CrossRefGoogle ScholarPubMed
20Goebel, H.H. and Warlo, I. (2001) Surplus protein myopathies. Neuromusc Disord 11, 3-6CrossRefGoogle ScholarPubMed
21Goebel, H.H. and Muller, H.D. (2006) Protein aggregate myopathies. Semin Pediatr Neurol 13, 96-103CrossRefGoogle ScholarPubMed
22Carrell, R.W. and Lomas, D.A. (1997) Conformational disease. Lancet 350, 134-138CrossRefGoogle ScholarPubMed
23Sherman, M.Y. and Goldberg, A.L. (2001) Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative disease. Neuron 29, 15-32CrossRefGoogle Scholar
24Ellis, R.J. and Pinheiro, T.J.T. (2002) Danger—misfolded proteins. Nature 416, 483-484CrossRefGoogle ScholarPubMed
25Crowther, D.C. (2002) Familial conformational diseases and dementias. Hum Mut 20, 1-14CrossRefGoogle ScholarPubMed
26Dagvadorj, A. et al. (2004) A series of West European patients with severe cardiac and skeletal myopathy associated with a de novo R406W mutation in desmin. J Neurol 251,143-149CrossRefGoogle Scholar
27Olivé, M. et al. (2007) Phenotypic patterns of desminopathy associated with three novel mutations in the desmin gene. Neuromusc Disord 17, 443-450CrossRefGoogle ScholarPubMed
28Goldfarb, L.G. et al. Intermediate filament diseases: desminopathy. In Cytoskeletal Disorders ( Laing, N., ed.), Eurekah/Landes Biosciences (in press)Google Scholar
29Selcen, D. and Engel, A.G. (2003) Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. Ann Neurol 54, 804-810CrossRefGoogle ScholarPubMed
30Olivé, M. et al. (2005) Myotilinopathy: refining the clinical and myopathological phenotype. Brain 128, 2315-2326CrossRefGoogle ScholarPubMed
31Ferreiro, A. et al. (2004) Desmin-related myopathy with Mallory body-like inclusions is caused by mutations of the selenoprotein N gene. Ann Neurol 55, 676-686CrossRefGoogle ScholarPubMed
32Watts, G.D. et al. (2004) Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin containing protein. Nat Genet 36, 377-381CrossRefGoogle ScholarPubMed
33Hübbers, C.U. et al. (2007) Pathological consequences of VCP mutations on human striated muscle. Brain 130, 381-393CrossRefGoogle ScholarPubMed
34Lazarides, E. (1980) Intermediate filaments as mechanical integrators of cellular space. Nature 283, 249-256Google ScholarPubMed
35Price, M.G. (1984) Molecular analysis of intermediate filament cytoskeleton – putative load-bearing structure. Am J Physiol 246, 566-572Google ScholarPubMed
36Hermannn, H. and Aebi, U. (2004) Intermediate filaments: molecular structure, assembly mechanisms and integration into functionally distinct intracellular scaffolds. Annu Rev Biochem 73, 749-789CrossRefGoogle Scholar
37Li, Z. et al. (1989) Human desmin-coding gene: complete nucleotide sequence: characterization and regulation of expresion during myogenesis and development. Gene 78, 243-254Google Scholar
38Weber, K. and Geisler, N. (1985) Intermediate filaments: structural conservation and divergence. Ann N Y Acad Sci 455, 126-154CrossRefGoogle ScholarPubMed
39Brown, J.H., Cohen, C. and Parry, D.A.D. (1996) Heptad breaks in α-helical coiled coils: stutters and stammers. Proteins 26, 134-1453.0.CO;2-G>CrossRefGoogle ScholarPubMed
40Herrmann, H. et al. (2000) The intermediate filament protein consensus motif helix 2B: its atomic structure and contribution to assembly. J Mol Biol 298, 817-832CrossRefGoogle ScholarPubMed
41Strelkov, S.V. et al. (2002) Conserved segments 1A and 2B of the intermediate filament dimer: their atomic structures and role in filament assembly. EMBO J 21, 1255-1266CrossRefGoogle ScholarPubMed
42Li, Z. et al. (1996) Cardiovascular lesions and skeletal myopathy in mice lacking desmin. Dev Biol 175, 362-366CrossRefGoogle ScholarPubMed
43Milner, D.J. et al. (1996) Disruption of muscle architecture and myocardial degeneration in mice lacking desmin. J Cell Biol 134, 1255-1270CrossRefGoogle ScholarPubMed
44Tornell, L.E. et al. (1997) Null mutation in the desmin gene gives rise to a cardiomyopathy. J Mol Cardiol 29, 2107-2124CrossRefGoogle Scholar
45Brakenhoff, R.H. et al. (1990) Human αB-crystallin (CRYA2) gene mapped to chromosome 11q12-q23. Hum Genet 85, 237-240CrossRefGoogle Scholar
46Golenhofen, N. et al. (1999) Binding of the stress protein αB-crystallin to cardiac myofibrils correlates with the degree of myocardial damage during ischemia/reperfusion in vivo. J Mol Cell Cardiol 31, 569-580CrossRefGoogle Scholar
47Horwitz, J. (2000) The function of alpha-crystallin in vision. Semin Cell Dev Biol 11, 53-60CrossRefGoogle ScholarPubMed
48Salmikangas, P. et al. (1999) Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy. Hum Mol Genet 8, 1329-1336CrossRefGoogle ScholarPubMed
49van der Ven, P. et al. (2000) Indications for a novel muscular dystrophy pathway: γ-filamin, the muscle-specific filamin isoform, interacts with myotilin. J Cell Biol 151, 235-248CrossRefGoogle ScholarPubMed
50Salmikangas, P. et al. (2003) Myotilin, the limb-girdle muscular dystrophy 1A (LGMD 1A) protein, cross-links actin filaments and controls sarcomere assembly. Hum Mol Genet 12, 189-203CrossRefGoogle Scholar
51von Nandelstadh, P. et al. (2005) Actin-organising properties of the muscular dystrophy protein myotilin. Exp Cell Res 310, 131-139CrossRefGoogle ScholarPubMed
52Gontier, Y. et al. (2005) The Z-disc proteins myotilin and FATZ-1 interact with each other and are connected to the sarcolemma via muscle-specific filamins. J Cell Sci 118, 3739-3749CrossRefGoogle Scholar
53Moza, M. et al. (2007) Targeted deletion of the muscular dystrophy gene myotilin does not perturb muscle structure or function in mice. Mol Cell Biol 27, 244-252CrossRefGoogle ScholarPubMed
54Faulkner, G. et al. (1999) ZASP: a new Z-band alternatively spliced PDZ-motif protein. J Cell Biol 146, 465-475CrossRefGoogle ScholarPubMed
55Au, Y. et al. (2004) Solution structure of ZASP PDZ domain: implications for sarcomere ultrastructure and enigma family redundancy. Structure 12, 611-622CrossRefGoogle ScholarPubMed
56Huang, C. et al. (2003) Characterization and in vivo functional analysis of splice variants of Cypher. J Biol Chem 278, 7360-7365CrossRefGoogle ScholarPubMed
57Van der Meer, D.L. et al. (2006) Zebrafish cipher is important for somite formation and heart development. Dev Biol 299, 356-372CrossRefGoogle Scholar
58Jani, K. and Schöck, F. (2007) Zasp is required for assembly of functional integrin adhesion sites. J Cell Biol 179, 1583-1597CrossRefGoogle ScholarPubMed
59Zhou, Q. et al. (2001) Ablation of cipher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy. J Cell Biol 155, 605-612CrossRefGoogle Scholar
60Arimura, T. et al. (2004) A Cypher/ZASP mutation associated with dilated cardiomyopathy alters the binding affinity to protein kinase C. J Biol Chem 279, 6746-6752CrossRefGoogle ScholarPubMed
61Himmel, M. et al. (2003) The limits of promiscuity: isoform-specific dimerization of filamins. Biochemistry 42, 30-39CrossRefGoogle ScholarPubMed
62van der Flier, A. and Sonnenberg, A. (2001) Structural and functional aspects of filamins. Biochim Biophys Acta 1538, 99-117CrossRefGoogle ScholarPubMed
63Thompson, T.G. et al. (2000) Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein. J Cell Biol 148, 115-126CrossRefGoogle ScholarPubMed
64van der Ven, P.F.M. et al. (2000) Characterization of muscle filamin isoforms suggests a possible role of gamma-filamin/ABP-L in sarcomeric Z-disc formation. Cell Motil Cytoskeleton 45, 149-1623.0.CO;2-G>CrossRefGoogle ScholarPubMed
65Takada, F. et al. (2001) Myozenin: an alpha-actinin- and gamma-filamin binding protein of skeletal muscle Z lines. Proc Natl Acad Sci U S A 98, 1595-1600Google ScholarPubMed
66Stossel, T.P. et al. (2001) Filamins as integrators of cell mechanics and signalling. Nat Rev Mol Cell Biol 2, 138-145CrossRefGoogle ScholarPubMed
67Xie, Z. et al. (1998) Molecular cloning of human ABPL, an actin-binding protein homologue. Biochem Biophys Res Commun 251, 914-919CrossRefGoogle ScholarPubMed
68van der Ven, P.F.M. et al. (2000) Indications for a novel muscular dystrophy pathway. Gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin. J Cell Biol 151, 235-248CrossRefGoogle ScholarPubMed
69Dalkilic, I. et al. (2006) Loss of filamin C (FLNc) results in severe defects in myogenesis and myotube structure. Mol Cell Biol 26, 6522-6634CrossRefGoogle ScholarPubMed
70Sjoberg, G. et al. (1999) Missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy and exerts a dominant negative effect on filament formation. Hum Mol Genet 8, 2191-2198CrossRefGoogle ScholarPubMed
71Li, D. et al. (1999) Desmin mutations responsible for idiopathic dilated cardiomyopathy. Circulation 100, 461-464CrossRefGoogle ScholarPubMed
72Sjoberg, G. et al. (1999) Missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy and exerts a dominant negative effect on fialament formation. Hum Mol Genet 8, 2191-2198CrossRefGoogle ScholarPubMed
73Park, K.Y. et al. (2000) Desmin splice variants causing cardiac and skeletal myopathy. J Med Genet 37, 851-857CrossRefGoogle ScholarPubMed
74Dagvadorj, A. et al. (2003) Respiratory insuficiency in desminopathy patients caused by introduction of proline residues in desmin C-terminal helical segment. Muscle Nerve 27, 669-675CrossRefGoogle Scholar
75Fidzianska, A. et al. (2005) A novel desmin R355P mutation causes cardiac and skeletal myopathy. Neuromusc Disord 15, 525-531CrossRefGoogle ScholarPubMed
76Vrabie, A. et al. (2005) The enlarging spectrum of desminopathies: new morphological findings, eastward geographic spread, novel exon 3 desmin mutation. Acta Neuropathol 109, 411-417CrossRefGoogle ScholarPubMed
77Bar, H. et al. (2007) Conspicuos involvement of desmin tail mutations in diverse cadiac and skeletal myopathies. Human Mut 28, 374-386CrossRefGoogle Scholar
78Dalakas, M.C. et al. (2003) Progressive skeletal myopathy, a phenotypic variant of desmin myopathy associated with desmin mutations. Neuromusc Disord 13, 252-258CrossRefGoogle ScholarPubMed
79Walter, M.C. et al. (2007) Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P. Brain 130, 1485-1496CrossRefGoogle Scholar
80Fardeau, M. et al. (1978) [A new familial muscular disorder demonstrated by the intra-sarcoplasmic accumulation of a granulo-filamentous material which is dense on electron microscopy (author's transl).] Rev Neurol (Paris) 134, 411-425 [Article in French]Google ScholarPubMed
81Fardeau, M. et al. (2000) [Familial myopathy with desmin storage seen as a granulo-filamentar, electron-dense material with mutation of the alphaB-cristallin gene.] Rev Neurol (Paris) 156, 497-504 [Article in French]Google ScholarPubMed
82Inagaki, N., Hayashi, T. and Arimura, T. (2006) αB-crystalin mutation in dilated cardiomyopathy. Biochem Biophys Res Commun 342, 379-386CrossRefGoogle ScholarPubMed
83Hauser, M.A. et al. (2000) Myotilin is mutated in limb girdle muscular dystrophy 1A. Hum Mol Genet 14, 2141-2147CrossRefGoogle Scholar
84Hauser, M.A. et al. (2002) Myotilin mutation found in second pedigree with LGMD 1 A. Am J Hum Genet 71, 1428-1432CrossRefGoogle Scholar
85Foroud, T. et al. (2005) A mutation in myotilin causes spheroid body myopathy. Neurology 65, 1936-1940CrossRefGoogle ScholarPubMed
86Fischer, D. et al. (2006) Different early pathogenesis in myotilinopathy compared to primary desminopathy. Neuromuscul Disord 16, 361-367CrossRefGoogle ScholarPubMed
87Berciano, J. et al. (2008) Autosomal dominant distal myopathy with a myotilin S55F mutation: sorting out the phenotype. J Neurol Neurosurg Psychiatry 79, 205-208CrossRefGoogle ScholarPubMed
88Griggs, R. et al. (2007) Zaspopathy in a large classic late-onset distal myopathy family. Brain 130, 1477-1484CrossRefGoogle Scholar
89Kley, R.A. et al. (2007) Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients. Brain 130, 3250-3264CrossRefGoogle ScholarPubMed
90Schröder, R. et al. (2003) On noxious desmin: functional effects of a novel heterozygous desmin insertion mutation on the extrasarcomeric desmin cytoskeleton and mitochondria. Hum Mol Genet 12, 657-669CrossRefGoogle ScholarPubMed
91Bar, H. et al. (2005) Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro. Hum Mol Genet 14, 1251-1260CrossRefGoogle ScholarPubMed
92Howman, E.V. et al. (2003) Syncoilin accumulation in two patients with desmin-related myopathy. Neuromusc Disord 13, 42-48Google ScholarPubMed
93Olivé, M. et al. (2003) Expression of intermediate filament protein synamin in myofibrillar myopathies and other muscle diseases. Acta Neuropathol 106, 1-7CrossRefGoogle ScholarPubMed
94Wang, X. et al. (2001) Mouse model of desmin-related cardiomyopathy. Circulation 103, 2402-2407CrossRefGoogle ScholarPubMed
95Yu, K.R. et al. (1994) Truncated desmin in PtK2 cells induces desmin-vimentin-cytokeratin coprecipitation, involution of intermediate filament networks and nuclear fragmentation: a model for many degenerative diseases. Proc Natl Acad Sci U S A 91, 2497-2501CrossRefGoogle Scholar
96Bar, H. et al. (2004) The biology of desmin filaments: how do mutations affect their structure, assembly and organisation. J Struct Biol 148, 137-152CrossRefGoogle ScholarPubMed
97Kaminska, A. et al. (2004) Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy. Hum Genet 114, 306-313CrossRefGoogle ScholarPubMed
98Bar, H. et al. (2006) Impact of disease mutations on the desmin filament assembly process. J Mol Biol 360, 1031-1042CrossRefGoogle ScholarPubMed
99Garvey, S.M. et al. (2006) Transgenic mice expressing the myotilin T57I mutation unite the pathology associated with LGMD1A and MFM. Hum Mol Genet 15, 2348-2362CrossRefGoogle ScholarPubMed
100Garvey, S.M. et al. (2008) Myotilin overexpression enhances myopathology in the LGMD1A mouse model. Muscle Nerve 37, 663-667CrossRefGoogle ScholarPubMed
101Wang, X. et al. (2001) Expression of R120G-αB-crystallin causes aberrant desmin and αB-crystallin aggregation and cardiomyopathy in mice. Circ Res 89, 84-91CrossRefGoogle ScholarPubMed
102Löwe, T. et al. (2007) The pathomechanism of filaminopathy: altered biochemical properties explain the cellular phenotype of a protein aggregation myopathy. Hum Mol Genet 16, 1351-1358CrossRefGoogle ScholarPubMed
103Barrachina, M. et al. (2007) Target genes of neuron-restrictive silencer factor are abnormally up-regulated in human myotilinopathy. Am J Pathol 171, 1312-1323CrossRefGoogle ScholarPubMed
104Schoenherr, C.J. and Anderson, D.J. (1995) The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science 267, 1360-1363CrossRefGoogle ScholarPubMed
105Bruce, A.W. et al. (2004) Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes. Proc Natl Acad Sci U S A 101,10458-10463CrossRefGoogle ScholarPubMed
106Glickman, M.H. and Ciechanover, A. (2002) The ubiquitin-proteasome proteolytic pathway: Destruction for the sake of construction. Physiol Rev 82, 373-428Google ScholarPubMed
107Kostova, Z. and Wolf, D.H. (2003) For whom the bell tolls: Protein quality control of the endoplasmic reticulum and the ubiquitin-proteasome connection. EMBO J 22, 2309-2317CrossRefGoogle ScholarPubMed
108Sijts, A., Zaiss, D. and Kloetzel, P.M. (2001) The role of the ubiquitin-proteasome pathway in MHC class I antigen processing: implications for vaccine design. Curr Mol Med 1, 665-676CrossRefGoogle ScholarPubMed
109Liu, J. et al. (2006) Impairment of the ubiquitin-proteasome system in desminopathy mouse hearts. FASEB J 20, 362-364CrossRefGoogle ScholarPubMed
110Jones, S.E. and Jomary, C. (2002) Clusterin. Int J Biochem Cell Biol 34, 427-431Google ScholarPubMed
111Freixes, M. et al. (2004) Clusterin solubility and aggregation in Creutzfeldt-Jakob disease. Acta Neuropathol 108, 295-301CrossRefGoogle ScholarPubMed
112Ferrer, I. et al. (2005) Involvement of clusterin and the aggresome in abnormal protein deposits in myofibrillar myopathies and inclusion body myositis. Brain Pathol 15, 101-108CrossRefGoogle ScholarPubMed
113Kopito, R.R. (2000) Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol 10, 524-530CrossRefGoogle ScholarPubMed
114Waelter, S. et al. (2001) Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol Biol Cell 12, 1393-1407CrossRefGoogle ScholarPubMed
115Riley, N.E. et al. (2002) The Mallory body as an aggresome: in vitro studies. Exp Mol Pathol 72, 17-23CrossRefGoogle ScholarPubMed
116Olanow, C.W. et al. (2004) Lewy-body formation in aggresome-related process: a hypothesis. Lancet Neurol 8, 496-503CrossRefGoogle Scholar
117Chávez-Zobel, A.T. et al. (2003) Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alpha-B-Crystallin mutant. Hum Mol Genet 12, 1609-1620Google ScholarPubMed
118Sanbe, A. et al. (2004) Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis. Proc Natl Acad Sci U S A 101, 10132-10136CrossRefGoogle ScholarPubMed
119van Leeuwen, F.W. et al. (1998) Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients. Science 279, 242-247CrossRefGoogle ScholarPubMed
120de Pril, R., Fischer, D.F. and van Leeuwen, F.W. (2006) Conformational diseases: an umbrella for various neurological disorders with an impaired ubiquitin-proteasome system. Neurobiol Aging 27, 515-523CrossRefGoogle ScholarPubMed
121French, B.A. et al. (2001) Aggresome formation in liver cells in response to different toxic mechanisms: role of the ubiquitin-proteasome pathway and the frameshift mutant of ubiquitin. Exp Mol Pathol 71, 241-246CrossRefGoogle ScholarPubMed
122Fratta, P. et al. (2004) Mutant ubiquitin UBB+1 is accumulated in sporadic inclusion-body myositis muscle fibers. Neurology 63, 1114-1117CrossRefGoogle ScholarPubMed
123Olivé, M. et al. (2008) Expression of mutant ubiquitin (UBB(+1)) and p62 in myotilinopathies and desminopathies. Neuropathol Appl Neurobiol 34, 76-87CrossRefGoogle ScholarPubMed
124Geetha, T. and Wooten, M.W. (2005) Structure and functional properties of the ubiquitin binding protein p62. FEBS Lett 512, 19-24Google Scholar
125Seibenhener, M.L., Geetha, T. and Wooten, M.W. (2007) Sequestrosome 1/p62 – more than just a scaffold. FEBS Lett 581, 175-179CrossRefGoogle Scholar
126Seibenhener, M.L. et al. (2004) Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol 24, 8055-8068CrossRefGoogle ScholarPubMed
127Zatloukal, K. et al. (2002) p62 is a common component of cytoplasmic inclusions in protein aggregation diseases. Am J Pathol 160, 255-263CrossRefGoogle ScholarPubMed
128Kuusisto, E., Parkkinen, L. and Alafuzoff, I. (2003) Morphogenesis of Lewy bodies: dissimilar incorporation of α-synuclein, ubiquitin and p62. J Neuropath Exp Neurol 62, 1241-1253Google ScholarPubMed
129Lange, S. et al. (2005) The kinase domain of titin controls muscle gene expression and protein turnover. Science 308, 1599-1603CrossRefGoogle ScholarPubMed
130Stagsted, J., Bendixen, E. and Andersen, H.J. (2004) Identification of specific oxidatively modified proteins in chicken muscles using a combined immunologic and proteomic approach. J Agric Food Chem 52, 3967-3974CrossRefGoogle ScholarPubMed
131Yan, L. et al. (2004) Gender-specific proteomic alterations in glycolytic and mitochondrial pathways in aging monkey hearts. J Mol Cell Cardiol 37,921-929CrossRefGoogle ScholarPubMed
132Rando, T.A. (2002) Oxidative stress and the pathogenesis of muscular dystrophies. Am J Phys Med Rehabil 81, S175-S186CrossRefGoogle ScholarPubMed
133Esposito, L.A. et al. (1999) Mitochondrial disease in mouse results in increased oxidative stress. Proc Natl Acad Sci U S A 96, 4820-4825CrossRefGoogle ScholarPubMed
134Haslbeck, K.M. et al. (2005) The RAGE pathway in inflammatory myopathies and limb girdle muscular dystrophy. Acta Neuropathol 110, 247-254CrossRefGoogle ScholarPubMed
135Rodriguez, M.C. and Tarnapolsky, M.A. (2003) Patients with dystrophinopathy show evidence of increased oxidative stress. Free Rad Biol Med 34,1217-1220CrossRefGoogle ScholarPubMed
136Janué, A., Olivé, M. and Ferrer, I. (2007) Oxidative stress in desminopathies and myotilinopathies: a link between oxidative damage and abnormal protein aggregation. Brain Pathol 17, 377-388CrossRefGoogle ScholarPubMed
137Buchwalow, I.B. et al. (2006) Nitric oxide synthase in muscular dystrophies: a re-evaluation. Acta Neuropathol 111, 579-588CrossRefGoogle ScholarPubMed
138Dudley, R.W.R. et al. (2006) Sarcolemmal damage in dystrophin deficiency is modulated by synergistic interactions between mechanical and oxidative/nitrosative stresses. Am J Pathol 168, 1276-1287CrossRefGoogle ScholarPubMed
139Poppek, D. and Grune, T. (2006) Proteasomal defense of oxidative protein modifications. Antioxid Redox Signal 8, 173-184CrossRefGoogle ScholarPubMed
140Divald, A. and Powell, S.R. (2006) Proteasome mediates removal of proteins oxidized during myocardial ischemia. Free Radic Biol Med 40, 156-164CrossRefGoogle ScholarPubMed
141Davies, K.J.A. (2001) Degradation of oxidized proteins by the 20S proteasome. Biochimie 83, 301-310CrossRefGoogle Scholar
142Grune, T. et al. (2004) Decreased proteolysis caused by protein aggregates, inclusion body, plaques, lipofuscin, ceroid, and aggresomes during oxidative stress, aging, and disease. J Biol Chem 36, 2519-2530Google ScholarPubMed
143Janué, A. et al. (2007) Desmin is oxidized and nitrated in affected muscles in myotilinopathies and desminopathies. J Neuropathol Exp Neurol 66, 711-723CrossRefGoogle ScholarPubMed
144Reimann, J. et al. (2003) Mitochondrial dysfunction in myofibrillar myopathy. Neuropathol Appl Neurobiol 29, 45-51Google ScholarPubMed
145Frank, D. et al. (2006) The sarcomeric Z-disc: a nodal point in signalling and disease. J Mol Med 84, 446-468Google ScholarPubMed

Further reading, resources and contacts

The entry for myofibrillar myopathies on the GENEreviews website, by D. Selcen and A.G. Engel, covers clinical and pathological aspects of these diseases; it also provides information on genetic testing and its use in diagnosis, management and genetic counselling of individuals and families with MFMs:

http://www.genereviews.orgGoogle Scholar
http://neuromuscular.wustl.eduGoogle Scholar