Abstract
Inclusion body myositis (IBM) is the most common myopathy in people over 50 years of age. It involves an inflammatory process that, paradoxically, does not respond to anti-inflammatory drugs. A key feature of IBM is the presence of amyloid-β-peptide aggregates called amyloid deposits, which are also characteristic of Alzheimer’s disease. The use of animals that mimic at least some characteristics of a disease has become very important in the quest to elucidate the molecular mechanisms underlying this and other pathogeneses. Although there are some transgenic mouse strains that recreate some aspects of IBM, in this review, we hypothesize that the great degree of similarity between nematode and human genes known to be involved in IBM as well as the considerable conservation of biological mechanisms across species is an important feature that must be taken into consideration when deciding on the use of this nematode as a model. Straightforward laboratory techniques (culture, transformation, gene knockdown, genetic screenings, etc.) as well as anatomical, physiological, and behavioral characteristics add to the value of this model. In the present work, we review evidence that supports the use of Caenorhabditis elegans as a biological model for IBM.
Similar content being viewed by others
References
Selkoe DJ (2007) Developing preventive therapies for chronic diseases: lessons learned from Alzheimer’s disease. Nutr Rev 65:S239–S243
Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 81:741–766
Engel WK, Askanas V (2006) Inclusion-body myositis: clinical, diagnostic, and pathologic aspects. Neurology 66:S20–S29
Askanas V, Engel WK (2007) Inclusion-body myositis, a multifactorial muscle disease associated with aging: current concepts of pathogenesis. Curr Opin Rheumatol 19:550–559
Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101–112
Brenner S (2003) Nature’s gift to science (Nobel lecture). Chembiochem 4:683–687
Culetto E, Sattelle DB (2000) A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes. Hum Mol Genet 9:869–877
Riddle DL, Blumenthal T, Meyer BJ, Priess JR (1997) C. elegans II. In: Riddle DL, Blumenthal T, Meyer BJ, Priess JR (eds) Cold Spring Harbor monograph series. Cold Spring Harbor Laboratory Press, Cold Spring Harbor
Hope IA (1999) C. elegans: a practical approach. In: Hope IA (ed) The practical approach series. Oxford University Press, Oxford, pp 69–95
Crawford D, Libina N, Kenyon C (2007) Caenorhabditis elegans integrates food and reproductive signals in lifespan determination. Aging Cell 6:715–721
Ghazi A, Henis-Korenblit S, Kenyon C (2007) Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A 104:5947–5952
Hansen M, Chandra A, Mitic LL, Onken B, Driscoll M, Kenyon C (2008) A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet 4:e24
Broue F, Liere P, Kenyon C, Baulieu EE (2007) A steroid hormone that extends the lifespan of Caenorhabditis elegans. Aging Cell 6:87–94
Hansen M, Hsu AL, Dillin A, Kenyon C (2005) New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet 1:119–128
Sulston JE, Horvitz HR (1977) Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 56:110–156
Horvitz HR (2003) Worms, life, and death (Nobel lecture). Chembiochem 4:697–711
Metzstein MM, Stanfield GM, Horvitz HR (1998) Genetics of programmed cell death in C. elegans: past, present and future. Trends Genet 14:410–416
Sulston JE (2003) Caenorhabditis elegans: the cell lineage and beyond (Nobel lecture). Chembiochem 4:688–696
Badrising UA, Maat-Schieman ML, van Houwelingen JC et al (2005) Inclusion body myositis. Clinical features and clinical course of the disease in 64 patients. J Neurol 252:1448–1454
Adams RD, Kakulas BA, Samaha FA (1965) A myopathy with cellular inclusions. Trans Am Neurol Assoc 90:213–216
Lotz BP, Engel AG, Nishino H, Stevens JC, Litchy WJ (1989) Inclusion body myositis. Observations in 40 patients. Brain 112(Pt 3):727–747
Figarella-Branger D, Civatte M, Bartoli C, Pellissier JF (2003) Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies. Muscle Nerve 28:659–682
Neville HE, Baumbach LL, Ringel SP, Russo LS Jr., Sujansky E, Garcia CA (1992) Familial inclusion body myositis: evidence for autosomal dominant inheritance. Neurology 42:897–902
McFerrin J, Engel WK, Askanas V (1998) Impaired innervation of cultured human muscle overexpressing betaAPP experimentally and genetically: relevance to inclusion-body myopathies. Neuroreport 9:3201–3205
Askanas V, Alvarez RB, Engel WK (1993) Beta-amyloid precursor epitopes in muscle fibers of inclusion body myositis. Ann Neurol 34:551–560
Askanas V, Engel WK (1993) New advances in inclusion-body myositis. Curr Opin Rheumatol 5:732–741
Needham M, Mastaglia FL, Garlepp MJ (2007) Genetics of inclusion-body myositis. Muscle Nerve 35:549–561
Koffman BM, Sivakumar K, Simonis T, Stroncek D, Dalakas MC (1998) HLA allele distribution distinguishes sporadic inclusion body myositis from hereditary inclusion body myopathies. J Neuroimmunol 84:139–142
Ranque-Francois B, Maisonobe T, Dion E et al (2005) Familial inflammatory inclusion body myositis. Ann Rheum Dis 64:634–637
Hubbers CU, Clemen CS, Kesper K et al (2007) Pathological consequences of VCP mutations on human striated muscle. Brain 130:381–393
Lindberg C, Trysberg E, Tarkowski A, Oldfors A (2003) Anti-T-lymphocyte globulin treatment in inclusion body myositis: a randomized pilot study. Neurology 61:260–262
Schmidt J, Rakocevic G, Raju R, Dalakas MC (2004) Upregulated inducible co-stimulator (ICOS) and ICOS-ligand in inclusion body myositis muscle: significance for CD8+ T cell cytotoxicity. Brain 127:1182–1190
Amemiya K, Granger RP, Dalakas MC (2000) Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time. Studies in repeated muscle biopsies. Brain 123(Pt 10):2030–2039
Raju R, Vasconcelos O, Granger R, Dalakas MC (2003) Expression of IFN-gamma-inducible chemokines in inclusion body myositis. J Neuroimmunol 141:125–131
Dalakas MC (2004) Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA 291:2367–2375
Askanas V, Engel WK, Bilak M, Alvarez RB, Selkoe DJ (1994) Twisted tubulofilaments of inclusion body myositis muscle resemble paired helical filaments of Alzheimer brain and contain hyperphosphorylated tau. Am J Pathol 144:177–187
Askanas V, Engel WK (2001) Inclusion-body myositis: newest concepts of pathogenesis and relation to aging and Alzheimer disease. J Neuropathol Exp Neurol 60:1–14
Askanas V, Engel WK (2002) Newest pathogenetic considerations in inclusion-body myositis: possible role of amyloid-beta, cholesterol, relation to aging and to Alzheimer’s disease. Curr Rheumatol Rep 4:427–433
Broccolini A, Engel WK, Alvarez RB, Askanas V (2000) Paired helical filaments of inclusion-body myositis muscle contain RNA and survival motor neuron protein. Am J Pathol 156:1151–1155
Wilczynski GM, Engel WK, Askanas V (2000) Association of active extracellular signal-regulated protein kinase with paired helical filaments of inclusion-body myositis muscle suggests its role in inclusion-body myositis tau phosphorylation. Am J Pathol 156:1835–1840
Kumamoto T, Ueyama H, Tsumura H, Toyoshima I, Tsuda T (2004) Expression of lysosome-related proteins and genes in the skeletal muscles of inclusion body myositis. Acta Neuropathol 107:59–65
Fukuchi K, Pham D, Hart M, Li L, Lindsey JR (1998) Amyloid-beta deposition in skeletal muscle of transgenic mice: possible model of inclusion body myopathy. Am J Pathol 153:1687–1693
Morgan C, Colombres M, Nunez MT, Inestrosa NC (2004) Structure and function of amyloid in Alzheimer’s disease. Prog Neurobiol 74:323–349
Soto C, Branes MC, Alvarez J, Inestrosa NC (1994) Structural determinants of the Alzheimer’s amyloid beta-peptide. J Neurochem 63:1191–1198
Askanas V, Engel WK, Alvarez RB (1993) Enhanced detection of Congo-Red-positive amyloid deposits in muscle fibers of inclusion body myositis and brain of Alzheimer’s disease using fluorescence technique. Neurology 43:1265–1267
Dalakas MC, Koffman B, Fujii M, Spector S, Sivakumar K, Cupler E (2001) A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM. Neurology 56:323–327
Barohn RJ, Herbelin L, Kissel JT et al (2006) Pilot trial of etanercept in the treatment of inclusion-body myositis. Neurology 66:S123–S124
Wolfe MS (2008) Gamma-secretase: structure, function, and modulation for Alzheimer’s disease. Curr Top Med Chem 8:2–8
Zhang YW, Xu H (2007) Molecular and cellular mechanisms for Alzheimer’s disease: understanding APP metabolism. Curr Mol Med 7:687–696
Jin LW, Hearn MG, Ogburn CE et al (1998) Transgenic mice over-expressing the C-99 fragment of betaPP with an alpha-secretase site mutation develop a myopathy similar to human inclusion body myositis. Am J Pathol 153:1679–1686
Tateyama M, Takeda A, Onodera Y et al (2003) Oxidative stress and predominant Abeta42(43) deposition in myopathies with rimmed vacuoles. Acta Neuropathol 105:581–585
Lunemann JD, Schmidt J, Schmid D et al (2007) Beta-amyloid is a substrate of autophagy in sporadic inclusion body myositis. Ann Neurol 61:476–483
Iqbal K, Alonso Adel C, Chen S et al (2005) Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta 1739:198–210
Mirabella M, Alvarez RB, Bilak M, Engel WK, Askanas V (1996) Difference in expression of phosphorylated tau epitopes between sporadic inclusion-body myositis and hereditary inclusion-body myopathies. J Neuropathol Exp Neurol 55:774–786
Pei JJ, Braak H, An WL et al (2002) Up-regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer’s disease. Brain Res Mol Brain Res 109:45–55
Gross SD, Anderson RA (1998) Casein kinase I: spatial organization and positioning of a multifunctional protein kinase family. Cell Signal 10:699–711
Flotow H, Graves PR, Wang AQ, Fiol CJ, Roeske RW, Roach PJ (1990) Phosphate groups as substrate determinants for casein kinase I action. J Biol Chem 265:14264–14269
Risnik VV, Adam G, Gusev NB, Friedrich P (1988) Casein kinases I and II bound to pig brain microtubules. Cell Mol Neurobiol 8:315–324
Li G, Yin H, Kuret J (2004) Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules. J Biol Chem 279:15938–15945
Ghoshal N, Smiley JF, DeMaggio AJ et al (1999) A new molecular link between the fibrillar and granulovacuolar lesions of Alzheimer’s disease. Am J Pathol 155:1163–1172
Kannanayakal TJ, Tao H, Vandre DD, Kuret J (2006) Casein kinase-1 isoforms differentially associate with neurofibrillary and granulovacuolar degeneration lesions. Acta Neuropathol 111:413–421
Price MA (2006) CKI, there’s more than one: casein kinase I family members in Wnt and Hedgehog signaling. Genes Dev 20:399–410
Caricasole A, Copani A, Caraci F et al (2004) Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer’s brain. J Neurosci 24:6021–6027
Inestrosa N, De Ferrari GV, Garrido JL et al (2002) Wnt signaling involvement in beta-amyloid-dependent neurodegeneration. Neurochem Int 41:341–344
De Ferrari GV, Inestrosa NC (2000) Wnt signaling function in Alzheimer’s disease. Brain Res Brain Res Rev 33:1–12
Kannanayakal TJ, Mendell JR, Kuret J (2008) Casein kinase 1 alpha associates with the tau-bearing lesions of inclusion body myositis. Neurosci Lett 431:141–145
Wolfe MS (2008) Gamma-secretase inhibition and modulation for Alzheimer’s disease. Curr Alzheimer Res 5:158–164
Evin G, Sernee MF, Masters CL (2006) Inhibition of gamma-secretase as a therapeutic intervention for Alzheimer’s disease: prospects, limitations and strategies. CNS Drugs 20:351–372
Askanas V, Engel WK, Yang CC, Alvarez RB, Lee VM, Wisniewski T (1998) Light and electron microscopic immunolocalization of presenilin 1 in abnormal muscle fibers of patients with sporadic inclusion-body myositis and autosomal-recessive inclusion-body myopathy. Am J Pathol 152:889–895
Vassar R (2004) BACE1: the beta-secretase enzyme in Alzheimer’s disease. J Mol Neurosci 23:105–114
Cole SL, Vassar R (2007) The Alzheimer’s disease beta-secretase enzyme, BACE1. Mol Neurodegener 2:22
Vattemi G, Engel WK, McFerrin J, Buxbaum JD, Pastorino L, Askanas V (2001) Presence of BACE1 and BACE2 in muscle fibres of patients with sporadic inclusion-body myositis. Lancet 358:1962–1964
Vattemi G, Engel WK, McFerrin J, Pastorino L, Buxbaum JD, Askanas V (2003) BACE1 and BACE2 in pathologic and normal human muscle. Exp Neurol 179:150–158
He W, Lu Y, Qahwash I, Hu XY, Chang A, Yan R (2004) Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation. Nat Med 10:959–965
Wojcik S, Engel WK, Yan R, McFerrin J, Askanas V (2007) NOGO is increased and binds to BACE1 in sporadic inclusion-body myositis and in A beta PP-overexpressing cultured human muscle fibers. Acta Neuropathol 114:517–526
Carson KA, Geula C, Mesulam MM (1991) Electron microscopic localization of cholinesterase activity in Alzheimer brain tissue. Brain Res 540:204–208
Geula C, Greenberg BD, Mesulam MM (1994) Cholinesterase activity in the plaques, tangles and angiopathy of Alzheimer’s disease does not emanate from amyloid. Brain Res 644:327–330
Inestrosa NC, Alarcon R (1998) Molecular interactions of acetylcholinesterase with senile plaques. J Physiol Paris 92:341–344
Alvarez A, Alarcon R, Opazo C et al (1998) Stable complexes involving acetylcholinesterase and amyloid-beta peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer’s fibrils. J Neurosci 18:3213–3223
Inestrosa NC, Alvarez A, Calderon F (1996) Acetylcholinesterase is a senile plaque component that promotes assembly of amyloid beta-peptide into Alzheimer’s filaments. Mol Psychiatry 1:359–361
Inestrosa NC, Alvarez A, Perez CA et al (1996) Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer’s fibrils: possible role of the peripheral site of the enzyme. Neuron 16:881–891
Alvarez A, Bronfman F, Perez CA, Vicente M, Garrido J, Inestrosa NC (1995) Acetylcholinesterase, a senile plaque component, affects the fibrillogenesis of amyloid-beta-peptides. Neurosci Lett 201:49–52
Alvarez A, Opazo C, Alarcon R, Garrido J, Inestrosa NC (1997) Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils. J Mol Biol 272:348–361
De Ferrari GV, Canales MA, Shin I, Weiner LM, Silman I, Inestrosa NC (2001) A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation. Biochemistry 40:10447–10457
Reyes AE, Chacon MA, Dinamarca MC, Cerpa W, Morgan C, Inestrosa NC (2004) Acetylcholinesterase–Abeta complexes are more toxic than Abeta fibrils in rat hippocampus: effect on rat beta-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss. Am J Pathol 164:2163–2174
Rees T, Hammond PI, Soreq H, Younkin S, Brimijoin S (2003) Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex. Neurobiol Aging 24:777–787
Inestrosa NC, Sagal JP, Colombres M (2005) Acetylcholinesterase interaction with Alzheimer amyloid beta. Subcell Biochem 38:299–317
Inestrosa NC, Dinamarca MC, Alvarez A (2008) Amyloid-cholinesterase interactions. Implications for Alzheimer’s disease. Febs J 275:625–632
Askanas V, Engel WK (2003) Unfolding story of inclusion-body myositis and myopathies: role of misfolded proteins, amyloid-beta, cholesterol, and aging. J Child Neurol 18:185–190
Frears ER, Stephens DJ, Walters CE, Davies H, Austen BM (1999) The role of cholesterol in the biosynthesis of beta-amyloid. Neuroreport 10:1699–1705
Jaworska-Wilczynska M, Wilczynski GM, Engel WK, Strickland DK, Weisgraber KH, Askanas V (2002) Three lipoprotein receptors and cholesterol in inclusion-body myositis muscle. Neurology 58:438–445
Askanas V, Mirabella M, Engel WK, Alvarez RB, Weisgraber KH (1994) Apolipoprotein E immunoreactive deposits in inclusion-body muscle diseases. Lancet 343:364–365
Mirabella M, Alvarez RB, Engel WK, Weisgraber KH, Askanas V (1996) Apolipoprotein E and apolipoprotein E messenger RNA in muscle of inclusion body myositis and myopathies. Ann Neurol 40:864–872
Inestrosa NC, Marzolo MP, Bonnefont AB (1998) Cellular and molecular basis of estrogen’s neuroprotection. Potential relevance for Alzheimer’s disease. Mol Neurobiol 17:73–86
Roses AD, Saunders AM (1997) Apolipoprotein E genotyping as a diagnostic adjunct for Alzheimer’s disease. Int Psychogeriatr 9(Suppl 1):277–288 discussion 317–221
Roses AD (2006) On the discovery of the genetic association of Apolipoprotein E genotypes and common late-onset Alzheimer disease. J Alzheimers Dis 9:361–366
Roses AD (1996) Apolipoprotein E alleles as risk factors in Alzheimer’s disease. Annu Rev Med 47:387–400
Caruso A, Motolese M, Iacovelli L et al (2006) Inhibition of the canonical Wnt signaling pathway by apolipoprotein E4 in PC12 cells. J Neurochem 98:364–371
Gossrau G, Gestrich B, Koch R et al (2004) Apolipoprotein E and alpha-1-antichymotrypsin polymorphisms in sporadic inclusion body myositis. Eur Neurol 51:215–220
Albrecht S, Bilbao JM (1993) Ubiquitin expression in inclusion body myositis. An immunohistochemical study. Arch Pathol Lab Med 117:789–793
Askanas V, Serdaroglu P, Engel WK, Alvarez RB (1991) Immunolocalization of ubiquitin in muscle biopsies of patients with inclusion body myositis and oculopharyngeal muscular dystrophy. Neurosci Lett 130:73–76
Mori H, Kondo J, Ihara Y (1987) Ubiquitin is a component of paired helical filaments in Alzheimer’s disease. Science 235:1641–1644
Perry G, Friedman R, Shaw G, Chau V (1987) Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc Natl Acad Sci U S A 84:3033–3036
Weihl CC, Miller SE, Hanson PI, Pestronk A (2007) Transgenic expression of inclusion body myopathy associated mutant p97/VCP causes weakness and ubiquitinated protein inclusions in mice. Hum Mol Genet 16:919–928
Fratta P, Engel WK, McFerrin J, Davies KJ, Lin SW, Askanas V (2005) Proteasome inhibition and aggresome formation in sporadic inclusion-body myositis and in amyloid-beta precursor protein-overexpressing cultured human muscle fibers. Am J Pathol 167:517–526
Parkin ET, Watt NT, Hussain I et al (2007) Cellular prion protein regulates beta-secretase cleavage of the Alzheimer’s amyloid precursor protein. Proc Natl Acad Sci U S A 104:11062–11067
Gacia M, Safranow K, Styczynska M et al (2006) Prion protein gene M129 allele is a risk factor for Alzheimer’s disease. J Neural Transm 113:1747–1751
Inestrosa NC, Cerpa W, Varela-Nallar L (2005) Copper brain homeostasis: role of amyloid precursor protein and prion protein. IUBMB Life 57:645–650
Varela-Nallar L, Toledo EM, Larrondo LF, Cabral AL, Martins VR, Inestrosa NC (2006) Induction of cellular prion protein gene expression by copper in neurons. Am J Physiol Cell Physiol 290:C271–281
Varela-Nallar L, Gonzalez A, Inestrosa NC (2006) Role of copper in prion diseases: deleterious or beneficial?. Curr Pharm Des 12:2587–2595
Zanusso G, Vattemi G, Ferrari S et al (2001) Increased expression of the normal cellular isoform of prion protein in inclusion-body myositis, inflammatory myopathies and denervation atrophy. Brain Pathol 11:182–189
Kovacs GG, Lindeck-Pozza E, Chimelli L et al (2004) Creutzfeldt-Jakob disease and inclusion body myositis: abundant disease-associated prion protein in muscle. Ann Neurol 55:121–125
Sarkozi E, Askanas V, Engel WK (1994) Abnormal accumulation of prion protein mRNA in muscle fibers of patients with sporadic inclusion-body myositis and hereditary inclusion-body myopathy. Am J Pathol 145:1280–1284
Huang S, Liang J, Zheng M et al (2007) Inducible overexpression of wild-type prion protein in the muscles leads to a primary myopathy in transgenic mice. Proc Natl Acad Sci U S A 104:6800–6805
Bilak M, Askanas V, Engel WK (1993) Strong immunoreactivity of alpha 1-antichymotrypsin co-localizes with beta-amyloid protein and ubiquitin in vacuolated muscle fibers of inclusion-body myositis. Acta Neuropathol 85:378–382
Vattemi G, Engel WK, McFerrin J, Askanas V (2003) Cystatin C colocalizes with amyloid-beta and coimmunoprecipitates with amyloid-beta precursor protein in sporadic inclusion-body myositis muscles. J Neurochem 85:1539–1546
Crawford FC, Freeman MJ, Schinka JA et al (2000) A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer’s disease. Neurology 55:763–768
Finckh U, von der Kammer H, Velden J et al (2000) Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease. Arch Neurol 57:1579–1583
Mao JJ, Katayama S, Watanabe C et al (2001) The relationship between alphaB-crystallin and neurofibrillary tangles in Alzheimer’s disease. Neuropathol Appl Neurobiol 27:180–188
Dabir DV, Trojanowski JQ, Richter-Landsberg C, Lee VM, Forman MS (2004) Expression of the small heat-shock protein alphaB-crystallin in tauopathies with glial pathology. Am J Pathol 164:155–166
Augusteyn RC (2004) alpha-crystallin: a review of its structure and function. Clin Exp Optom 87:356–366
Horwitz J (2003) Alpha-crystallin. Exp Eye Res 76:145–153
Stege GJ, Renkawek K, Overkamp PS et al (1999) The molecular chaperone alphaB-crystallin enhances amyloid beta neurotoxicity. Biochem Biophys Res Commun 262:152–156
Banwell BL, Engel AG (2000) AlphaB-crystallin immunolocalization yields new insights into inclusion body myositis. Neurology 54:1033–1041
Wojcik S, Engel WK, McFerrin J, Paciello O, Askanas V (2006) AbetaPP-overexpression and proteasome inhibition increase alphaB-crystallin in cultured human muscle: relevance to inclusion-body myositis. Neuromuscul Disord 16:839–844
Wilhelmus MM, de Waal RM, Verbeek MM (2007) Heat shock proteins and amateur chaperones in amyloid-Beta accumulation and clearance in Alzheimer’s disease. Mol Neurobiol 35:203–216
Gonzalez-Cadavid NF, Bhasin S (2004) Role of myostatin in metabolism. Curr Opin Clin Nutr Metab Care 7:451–457
Wojcik S, Nogalska A, McFerrin J, Engel WK, Oledzka G, Askanas V (2007) Myostatin precursor protein is increased and associates with amyloid-beta precursor protein in inclusion-body myositis culture model. Neuropathol Appl Neurobiol 33:238–242
Wojcik S, Engel WK, McFerrin J, Askanas V (2005) Myostatin is increased and complexes with amyloid-beta within sporadic inclusion-body myositis muscle fibers. Acta Neuropathol 110:173–177
Miranda S, Opazo C, Larrondo LF et al (2000) The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer’s disease. Prog Neurobiol 62:633–648
Thomas T, Thomas G, McLendon C, Sutton T, Mullan M (1996) Beta-amyloid-mediated vasoactivity and vascular endothelial damage. Nature 380:168–171
Opazo C, Huang X, Cherny RA et al (2002) Metalloenzyme-like activity of Alzheimer’s disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H(2)O(2). J Biol Chem 277:40302–40308
Behl C, Davis JB, Lesley R, Schubert D (1994) Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77:817–827
Santos MJ, Quintanilla RA, Toro A et al (2005) Peroxisomal proliferation protects from beta-amyloid neurodegeneration. J Biol Chem 280:41057–41068
Ruiz FH, Gonzalez M, Bodini M, Opazo C, Inestrosa NC (1999) Cysteine 144 is a key residue in the copper reduction by the beta-amyloid precursor protein. J Neurochem 73:1288–1292
Oldfors A, Moslemi AR, Jonasson L, Ohlsson M, Kollberg G, Lindberg C (2006) Mitochondrial abnormalities in inclusion-body myositis. Neurology 66:S49–S55
Fukuchi K, Ho L, Younkin SG et al (1996) High levels of circulating beta-amyloid peptide do not cause cerebral beta-amyloidosis in transgenic mice. Am J Pathol 149:219–227
Fukuchi K, Li L, Hart M, Lindsey JR (2000) Accumulation of amyloid-beta protein in exocrine glands of transgenic mice overexpressing a carboxyl terminal portion of amyloid protein precursor. Int J Exp Pathol 81:231–239
Sugarman MC, Yamasaki TR, Oddo S et al (2002) Inclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscle. Proc Natl Acad Sci U S A 99:6334–6339
Sugarman MC, Kitazawa M, Baker M, Caiozzo VJ, Querfurth HW, LaFerla FM (2006) Pathogenic accumulation of APP in fast twitch muscle of IBM patients and a transgenic model. Neurobiol Aging 27:423–432
Kitazawa M, Green KN, Caccamo A, LaFerla FM (2006) Genetically augmenting Abeta42 levels in skeletal muscle exacerbates inclusion body myositis-like pathology and motor deficits in transgenic mice. Am J Pathol 168:1986–1997
Kitazawa M, Trinh DN, Laferla FM (2008) Inflammation induces tau pathology in inclusion body myositis model via glycogen synthase kinase-3beta. Ann Neurol 64:15–24
Feany MB (2000) Studying human neurodegenerative diseases in flies and worms. J Neuropathol Exp Neurol 59:847–856
Link CD (2001) Transgenic invertebrate models of age-associated neurodegenerative diseases. Mech Ageing Dev 122:1639–1649
Link CD (2005) Invertebrate models of Alzheimer’s disease. Genes Brain Behav 4:147–156
Miguel-Aliaga I, Culetto E, Walker DS, Baylis HA, Sattelle DB, Davies KE (1999) The Caenorhabditis elegans orthologue of the human gene responsible for spinal muscular atrophy is a maternal product critical for germline maturation and embryonic viability. Hum Mol Genet 8:2133–2143
Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC (1994) Green fluorescent protein as a marker for gene expression. Science 263:802–805
Chapin A, Correa P, Maguire M, Kohn R (2007) Synaptic neurotransmission protein UNC-13 affects RNA interference in neurons. Biochem Biophys Res Commun 354:1040–1044
Kamath RS, Ahringer J (2003) Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30:313–321
Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811
Faber PW, Alter JR, MacDonald ME, Hart AC (1999) Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron. Proc Natl Acad Sci U S A 96:179–184
Satyal SH, Schmidt E, Kitagawa K et al (2000) Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans. Proc Natl Acad Sci U S A 97:5750–5755
Lakso M, Vartiainen S, Moilanen AM et al (2003) Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein. J Neurochem 86:165–172
Kuwahara T, Koyama A, Gengyo-Ando K et al (2006) Familial Parkinson mutant alpha-synuclein causes dopamine neuron dysfunction in transgenic Caenorhabditis elegans. J Biol Chem 281:334–340
Link CD (1995) Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans. Proc Natl Acad Sci U S A 92:9368–9372
Waterston RH (1998) The nematode Caenorhabditis elegans. In: Wood WB (ed) Cold Spring Harbor monograph series. Cold Spring Harbor Laboratory, NY, pp 281–335
Moerman DG, Williams BD (2006) Sarcomere assembly in C. elegans muscle. WormBook 16:1–16
Francis R, Waterston RH (1991) Muscle cell attachment in Caenorhabditis elegans. J Cell Biol 114:465–479
Lecroisey C, Segalat L, Gieseler K (2007) The C. elegans dense body: anchoring and signaling structure of the muscle. J Muscle Res Cell Motil 28:79–87
Epstein HF (1990) Genetic analysis of myosin assembly in Caenorhabditis elegans. Mol Neurobiol 4:1–25
Castellani L, Vibert P, Cohen C (1983) Structure of myosin/paramyosin filaments from a molluscan smooth muscle. J Mol Biol 167:853–872
Beall CJ, Sepanski MA, Fyrberg EA (1989) Genetic dissection of Drosophila myofibril formation: effects of actin and myosin heavy chain null alleles. Genes Dev 3:131–140
Lu MH, DiLullo C, Schultheiss T et al (1992) The vinculin/sarcomeric-alpha-actinin/alpha-actin nexus in cultured cardiac myocytes. J Cell Biol 117:1007–1022
Francis GR, Waterston RH (1985) Muscle organization in Caenorhabditis elegans: localization of proteins implicated in thin filament attachment and I-band organization. J Cell Biol 101:1532–1549
Gettner SN, Kenyon C, Reichardt LF (1995) Characterization of beta pat-3 heterodimers, a family of essential integrin receptors in C. elegans. J Cell Biol 129:1127–1141
Daigle I, Li C (1993) apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. Proc Natl Acad Sci U S A 90:12045–12049
Styren SD, Hamilton RL, Styren GC, Klunk WE (2000) X-34, a fluorescent derivative of Congo Red: a novel histochemical stain for Alzheimer’s disease pathology. J Histochem Cytochem 48:1223–1232
Link CD, Taft A, Kapulkin V et al (2003) Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer’s disease model. Neurobiol Aging 24:397–413
Fonte V, Kapulkin V, Taft A, Fluet A, Friedman D, Link CD (2002) Interaction of intracellular beta amyloid peptide with chaperone proteins. Proc Natl Acad Sci U S A 99:9439–9444
Stringham EG, Jones D, Candido EP (1992) Expression of the polyubiquitin-encoding gene (ubq-1) in transgenic Caenorhabditis elegans. Gene 113:165–173
Link CD, Cypser JR, Johnson CJ, Johnson TE (1999) Direct observation of stress response in Caenorhabditis elegans using a reporter transgene. Cell Stress Chaperones 4:235–242
Fonte V, Kipp DR, Yerg J 3rd et al (2008) Suppression of in vivo beta-amyloid peptide toxicity by overexpression of the HSP-16.2 small chaperone protein. J Biol Chem 283:784–791
Westlund B, Parry D, Clover R, Basson M, Johnson CD (1999) Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling. Proc Natl Acad Sci U S A 96:2497–2502
Levitan D, Doyle TG, Brousseau D et al (1996) Assessment of normal and mutant human presenilin function in Caenorhabditis elegans. Proc Natl Acad Sci U S A 93:14940–14944
Cinar HN, Sweet KL, Hosemann KE, Earley K, Newman AP (2001) The SEL-12 presenilin mediates induction of the Caenorhabditis elegans uterine pi cell fate. Dev Biol 237:173–182
Eimer S, Donhauser R, Baumeister R (2002) The Caenorhabditis elegans presenilin sel-12 is required for mesodermal patterning and muscle function. Dev Biol 251:178–192
Wittenburg N, Eimer S, Lakowski B, Rohrig S, Rudolph C, Baumeister R (2000) Presenilin is required for proper morphology and function of neurons in C. elegans. Nature 406:306–309
Arpagaus M, Combes D, Culetto E et al (1998) Four acetylcholinesterase genes in the nematode Caenorhabditis elegans. J Physiol Paris 92:363–367
Grauso M, Culetto E, Combes D, Fedon Y, Toutant JP, Arpagaus M (1998) Existence of four acetylcholinesterase genes in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. FEBS Lett 424:279–284
Combes D, Fedon Y, Toutant JP, Arpagaus M (2003) Multiple ace genes encoding acetylcholinesterases of Caenorhabditis elegans have distinct tissue expression. Eur J Neurosci 18:497–512
Drake J, Link CD, Butterfield DA (2003) Oxidative stress precedes fibrillar deposition of Alzheimer’s disease amyloid beta-peptide (1-42) in a transgenic Caenorhabditis elegans model. Neurobiol Aging 24:415–420
Triguero L, Singh R, Prabhakar R (2008) Molecular dynamics study to investigate the effect of chemical substitutions of methionine 35 on the secondary structure of the amyloid beta (Abeta(1-42)) monomer in aqueous solution. J Phys Chem B 112:2159–2167
Hou L, Shao H, Zhang Y et al (2004) Solution NMR studies of the A beta(1-40) and A beta(1-42) peptides establish that the Met35 oxidation state affects the mechanism of amyloid formation. J Am Chem Soc 126:1992–2005
Bitan G, Tarus B, Vollers SS et al (2003) A molecular switch in amyloid assembly: Met35 and amyloid beta-protein oligomerization. J Am Chem Soc 125:15359–15365
Fay DS, Fluet A, Johnson CJ, Link CD (1998) In vivo aggregation of beta-amyloid peptide variants. J Neurochem 71:1616–1625
Yatin SM, Varadarajan S, Link CD, Butterfield DA (1999) In vitro and in vivo oxidative stress associated with Alzheimer’s amyloid beta-peptide (1-42). Neurobiol Aging 20:325–330 discussion 339–342
Hensley K, Hall N, Subramaniam R et al (1995) Brain regional correspondence between Alzheimer’s disease histopathology and biomarkers of protein oxidation. J Neurochem 65:2146–2156
Boyd-Kimball D, Poon HF, Lynn BC et al (2006) Proteomic identification of proteins specifically oxidized in Caenorhabditis elegans expressing human Abeta(1-42): implications for Alzheimer’s disease. Neurobiol Aging 27:1239–1249
Mortimore GE, Schworer CM (1977) Induction of autophagy by amino-acid deprivation in perfused rat liver. Nature 270:174–176
Yu WH, Kumar A, Peterhoff C et al (2004) Autophagic vacuoles are enriched in amyloid precursor protein-secretase activities: implications for beta-amyloid peptide over-production and localization in Alzheimer’s disease. Int J Biochem Cell Biol 36:2531–2540
Yu WH, Cuervo AM, Kumar A et al (2005) Macroautophagy—a novel beta-amyloid peptide-generating pathway activated in Alzheimer’s disease. J Cell Biol 171:87–98
Nixon RA (2007) Autophagy, amyloidogenesis and Alzheimer disease. J Cell Sci 120:4081–4091
Florez-McClure ML, Hohsfield LA, Fonte G, Bealor MT, Link CD (2007) Decreased insulin-receptor signaling promotes the autophagic degradation of beta-amyloid peptide in C. elegans. Autophagy 3:569–580
Wu Y, Wu Z, Butko P et al (2006) Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans. J Neurosci 26:13102–13113
Soto C, Castano EM, Frangione B, Inestrosa NC (1995) The alpha-helical to beta-strand transition in the amino-terminal fragment of the amyloid beta-peptide modulates amyloid formation. J Biol Chem 270:3063–3067
Nilsberth C, Westlind-Danielsson A, Eckman CB et al (2001) The ‘Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Abeta protofibril formation. Nat Neurosci 4:887–893
Grez PA (2005) Obtención y análisis de Cepas Transgénicas de C. elegans. Expresión de péptido Aβ wild-type y sus variantes NIC y Arctic Facultad de Ciencias Químicas y Farmacéuticas. Universidad de Chile, Santiago, Chile, p 56
Praitis V, Casey E, Collar D, Austin J (2001) Creation of low-copy integrated transgenic lines in Caenorhabditis elegans. Genetics 157:1217–1226
Deibel MA, Ehmann WD, Markesbery WR (1996) Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer’s disease: possible relation to oxidative stress. J Neurol Sci 143:137–142
Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998) Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci 158:47–52
Candy JM, Oakley AE, Klinowski J et al (1986) Aluminosilicates and senile plaque formation in Alzheimer’s disease. Lancet 1:354–357
Lovell MA, Ehmann WD, Markesbery WR (1993) Laser microprobe analysis of brain aluminum in Alzheimer’s disease. Ann Neurol 33:36–42
Perl DP, Brody AR (1980) Alzheimer’s disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science 208:297–299
Landsberg JP, McDonald B, Watt F (1992) Absence of aluminium in neuritic plaque cores in Alzheimer’s disease. Nature 360:65–68
Chafi AH, Hauw JJ, Rancurel G, Berry JP, Galle C (1991) Absence of aluminium in Alzheimer’s disease brain tissue: electron microprobe and ion microprobe studies. Neurosci Lett 123:61–64
Good PF, Perl DP, Bierer LM, Schmeidler J (1992) Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer’s disease: a laser microprobe (LAMMA) study. Ann Neurol 31:286–292
Ferreira PC, Piai Kde A, Takayanagui AM, Segura-Munoz SI (2008) Aluminum as a risk factor for Alzheimer’s disease. Rev Lat Am Enfermagem 16:151–157
Sparks DL, Friedland R, Petanceska S et al (2006) Trace copper levels in the drinking water, but not zinc or aluminum influence CNS Alzheimer-like pathology. J Nutr Health Aging 10:247–254
Miu AC, Benga O (2006) Aluminum and Alzheimer’s disease: a new look. J Alzheimers Dis 10:179–201
Drago D, Bettella M, Bolognin S et al (2008) Potential pathogenic role of beta-amyloid(1-42)-aluminum complex in Alzheimer’s disease. Int J Biochem Cell Biol 40:731–746
Rodella LF, Ricci F, Borsani E et al (2008) Aluminium exposure induces Alzheimer’s disease-like histopathological alterations in mouse brain. Histol Histopathol 23:433–439
Bush AI, Pettingell WH, Multhaup G et al (1994) Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 265:1464–1467
Bush AI, Pettingell WH Jr., Paradis MD, Tanzi RE (1994) Modulation of A beta adhesiveness and secretase site cleavage by zinc. J Biol Chem 269:12152–12158
Cherny RA, Atwood CS, Xilinas ME et al (2001) Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron 30:665–676
Ritchie CW, Bush AI, Mackinnon A et al (2003) Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch Neurol 60:1685–1691
White AR, Zheng H, Galatis D et al (1998) Survival of cultured neurons from amyloid precursor protein knock-out mice against Alzheimer’s amyloid-beta toxicity and oxidative stress. J Neurosci 18:6207–6217
Maynard CJ, Cappai R, Volitakis I et al (2002) Overexpression of Alzheimer’s disease amyloid-beta opposes the age-dependent elevations of brain copper and iron. J Biol Chem 277:44670–44676
Bayer TA, Schafer S, Simons A et al (2003) Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Abeta production in APP23 transgenic mice. Proc Natl Acad Sci U S A 100:14187–14192
Phinney AL, Drisaldi B, Schmidt SD et al (2003) In vivo reduction of amyloid-beta by a mutant copper transporter. Proc Natl Acad Sci U S A 100:14193–14198
Cerpa WF, Barria MI, Chacon MA et al (2004) The N-terminal copper-binding domain of the amyloid precursor protein protects against Cu2+ neurotoxicity in vivo. FASEB J 18:1701–1703
Cerpa W, Varela-Nallar L, Reyes AE, Minniti AN, Inestrosa NC (2005) Is there a role for copper in neurodegenerative diseases?. Mol Aspects Med 26:405–420
Bush AI, Tanzi RE (2008) Therapeutics for Alzheimer’s disease based on the metal hypothesis. Neurotherapeutics 5:421–432
Tsuruta Y, Furuta A, Taniguchi N, Yamada T, Kira J, Iwaki T (2002) Increased expression of manganese superoxide dismutase is associated with that of nitrotyrosine in myopathies with rimmed vacuoles. Acta Neuropathol 103:59–65
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rebolledo, D.L., Minniti, A.N., Grez, P.M. et al. Inclusion Body Myositis: A View from the Caenorhabditis elegans Muscle. Mol Neurobiol 38, 178–198 (2008). https://doi.org/10.1007/s12035-008-8041-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-008-8041-0