Molecular pathology and pathogenesis of inclusion‐body myositis

We summarize the molecular phenotype, diagnostic criteria, and the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion‐body myositis (s‐IBM), a muscle disease usually of persons over age 50. On the basis of our research, several processes seem to be important in relation to the still‐speculative pathogenesis: 1) increased transcription and accumulation of amyloid‐β precursor protein (AβPP), and accumulation of its proteolytic fragment Aβ; 2) abnormal accumulation of cholesterol, caveolin‐1, and apolipoprotein E; 3) oxidative stress; 4) accumulations of intramuscle fiber multiprotein aggregates; and 5) evidence that unfolded/misfolded proteins participate in s‐IBM pathogenesis. Our basic hypothesis is that overexpression of AβPP within the aging muscle fibers is an early upstream event causing a subsequent pathogenic cascade. Microsc. Res. Tech. 67:114–120, 2005. © 2005 Wiley‐Liss, Inc.

[1]  J. Buxbaum,et al.  BACE1 and BACE2 in pathologic and normal human muscle , 2003, Experimental Neurology.

[2]  J. Buxbaum,et al.  Presence of BACE1 and BACE2 in muscle fibres of patients with sporadic inclusion-body myositis , 2001, The Lancet.

[3]  W. Engel,et al.  Use of anti‐neurofilament antibody to identify paired‐helical filaments in inclusion‐body myositis , 1996, Annals of neurology.

[4]  W. Engel,et al.  Impaired innervation of cultured human muscle overexpressing βAPP experimentally and genetically: relevance to inclusion‐body myopathies , 1998, Neuroreport.

[5]  W. Engel,et al.  Redox factor-1 in muscle biopsies of patients with inclusion-body myositis , 2000, Neuroscience Letters.

[6]  W. Engel,et al.  Endoplasmic reticulum stress and unfolded protein response in inclusion body myositis muscle. , 2004, The American journal of pathology.

[7]  W. Engel,et al.  Difference in Expression of Phosphorylated Tau Epitopes between Sporadic Inclusion‐body Myositis and Hereditary Inclusion‐body Myopathies , 1996, Journal of neuropathology and experimental neurology.

[8]  R. Prayson,et al.  Ubiquitin immunostaining and inclusion body myositis: study of 30 patients with inclusion body myositis. , 1997, Human pathology.

[9]  W. Engel,et al.  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. , 1998, The American journal of pathology.

[10]  F. Grosveld,et al.  Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients. , 1998, Science.

[11]  W. Surewicz,et al.  The Role of Disulfide Bridge in the Folding and Stability of the Recombinant Human Prion Protein* , 2001, The Journal of Biological Chemistry.

[12]  D. Hilton‐Jones.  Inflammatory muscle diseases , 2001, Current opinion in neurology.

[13]  C. Southan,et al.  ASP1 (BACE2) Cleaves the Amyloid Precursor Protein at the β-Secretase Site , 2000, Molecular and Cellular Neuroscience.

[14]  Aaron Ciechanover,et al.  The Ubiquitin Proteasome System in Neurodegenerative Diseases Sometimes the Chicken, Sometimes the Egg , 2003, Neuron.

[15]  W. Engel,et al.  beta-Amyloid precursor protein mRNA is increased in inclusion-body myositis muscle. , 1993, Neuroreport.

[16]  W. Engel,et al.  Rapid examination of muscle tissue , 1963, Neurology.

[17]  J R Lindsey,et al.  Amyloid-beta deposition in skeletal muscle of transgenic mice: possible model of inclusion body myopathy. , 1998, The American journal of pathology.

[18]  J. Growdon,et al.  Elevation of cystatin C in susceptible neurons in Alzheimer's disease. , 2001, The American journal of pathology.

[19]  W. Engel,et al.  Novel cytoplasmic immunolocalization of RNA polymerase II in inclusion-body myositis muscle , 2001, Neuroreport.

[20]  Sangram S. Sisodia,et al.  γ-Secretase, notch, Aβ and alzheimer's disease: Where do the presenilins fit in? , 2002, Nature Reviews Neuroscience.

[21]  S. Silberstein,et al.  Acute migraine treatment with droperidol , 2003, Neurology.

[22]  D. Dickson,et al.  Recognition of tau epitopes by anti-neurofilament antibodies that bind to Alzheimer neurofibrillary tangles. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Amy S. Lee,et al.  The glucose-regulated proteins: stress induction and clinical applications. , 2001, Trends in biochemical sciences.

[24]  W. Engel,et al.  Proposed pathogenetic cascade of inclusion-body myositis: importance of amyloid-&bgr;, misfolded proteins, predisposing genes, and aging , 2003, Current opinion in rheumatology.

[25]  W. Klein.  ADDLs & protofibrils—the missing links? , 2002, Neurobiology of Aging.

[26]  B. Ghetti,et al.  Codeposition of Cystatin C with Amyloid‐β Protein in the Brain of Alzheimer Disease Patients , 2001, Journal of neuropathology and experimental neurology.

[27]  H. Paulson,et al.  Protein aggregation and the ubiquitin proteasome pathway: gaining the UPPer hand on neurodegeneration. , 2003, Current opinion in genetics & development.

[28]  Min Goo Lee,et al.  Dynamic Association of Proteasomal Machinery with the Centrosome , 1999, The Journal of cell biology.

[29]  E. Hol,et al.  Molecular misreading: a new type of transcript mutation expressed during aging , 2000, Neurobiology of Aging.

[30]  W. Engel,et al.  Sporadic inclusion-body myositis and its similarities to Alzheimer disease brain. Recent approaches to diagnosis and pathogenesis, and relation to aging. , 1998, Scandinavian journal of rheumatology.

[31]  W. Engel,et al.  β‐Amyloid precursor epitopes in muscle fibers of inclusion body myositis , 1993 .

[32]  W. Engel,et al.  Novel Immunolocalization of α‐Synuclein in Human Muscle of Inclusion‐Body Myositis, Regenerating and Necrotic Muscle Fibers, and at Neuromuscular Junctions , 2000, Journal of neuropathology and experimental neurology.

[33]  H. Atkins,et al.  Suppressing immunity in advancing MS , 2004, Neurology.

[34]  C. Warren Olanow,et al.  Altered Proteasomal Function in Sporadic Parkinson's Disease , 2003, Experimental Neurology.

[35]  K. Mori.  Tripartite Management of Unfolded Proteins in the Endoplasmic Reticulum , 2000, Cell.

[36]  George M. Martin,et al.  Transgenic Mice Over-Expressing the C-99 Fragment of βPP with an α-Secretase Site Mutation Develop a Myopathy Similar to Human Inclusion Body Myositis , 1998 .

[37]  W. Engel,et al.  Enhanced detection of Congo‐red‐positive amyloid deposits in muscle fibers of inclusion body myositis and brain of Alzheimer's disease using fluorescence technique , 1993, Neurology.

[38]  E. Bennett,et al.  Global impairment of the ubiquitin-proteasome system by nuclear or cytoplasmic protein aggregates precedes inclusion body formation. , 2005, Molecular cell.

[39]  W. Baumeister,et al.  The 26S proteasome: a molecular machine designed for controlled proteolysis. , 1999, Annual review of biochemistry.

[40]  W. Engel,et al.  Does Overexpression of βAPP in Aging Muscle Have a Pathogenic Role and a Relevance to Alzheimer’s Disease? : Clues from Inclusion Body Myositis, Cultured Human Muscle, and Transgenic Mice , 1998 .

[41]  M. Dalakas.  The molecular and cellular pathology of inflammatory muscle diseases. , 2001, Current opinion in pharmacology.

[42]  K. Hall,et al.  Serum cholesterol, APOE genotype, and the risk of Alzheimer’s disease: A population-based study of African Americans , 2000, Neurology.

[43]  W. Engel,et al.  Inclusion‐Body Myositis: Newest Concepts of Pathogenesis and Relation to Aging and Alzheimer Disease , 2001, Journal of neuropathology and experimental neurology.

[44]  R. Barbour,et al.  Purification and cloning of amyloid precursor protein β-secretase from human brain , 1999, Nature.

[45]  K. Lindenberg,et al.  Protein surveillance machinery in brains with spinocerebellar ataxia type 3: Redistribution and differential recruitment of 26S proteasome subunits and chaperones to neuronal intranuclear inclusions , 2002, Annals of neurology.

[46]  R. Kopito,et al.  Aggresomes, inclusion bodies and protein aggregation. , 2000, Trends in cell biology.

[47]  K. Borden.  Structure/function in neuroprotection and apoptosis , 1998, Annals of neurology.

[48]  W. Markesbery,et al.  Impaired Proteasome Function in Alzheimer's Disease , 2000, Journal of neurochemistry.

[49]  K. Weisgraber,et al.  Apolipoprotein E and apolipoprotein E messenger RNA in muscle of inclusion body myositis and myopathies , 1996, Annals of neurology.

[50]  J. Yesavage,et al.  α2 Macroglobulin and the risk of Alzheimer’s disease , 2000, Neurology.

[51]  C. Fielding,et al.  Cholesterol and caveolae: structural and functional relationships. , 2000, Biochimica et biophysica acta.

[52]  W. Engel,et al.  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. , 2000, The American journal of pathology.

[53]  W. Engel,et al.  βAPP gene transfer into cultured human muscle induces inclusion‐body myositis aspects , 1997 .

[54]  R. Kaufman.  Orchestrating the unfolded protein response in health and disease. , 2002, The Journal of clinical investigation.

[55]  F. Acquati,et al.  The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the Down critical region , 2000, FEBS letters.

[56]  J. Mendell,et al.  Amyloid filaments in inclusion body myositis. Novel findings provide insight into nature of filaments. , 1991, Archives of neurology.

[57]  E. Hol,et al.  Mutant ubiquitin found in neurodegenerative disorders is a ubiquitin fusion degradation substrate that blocks proteasomal degradation , 2002, The Journal of cell biology.

[58]  W. Engel,et al.  Immunolocalization of transcription factor NF-κB in inclusion-body myositis muscle and at normal human neuromuscular junctions , 1998, Neuroscience Letters.

[59]  R. Terry.  The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis. , 1996, Journal of neuropathology and experimental neurology.

[60]  J. Trejo,et al.  A direct role for protein kinase C and the transcription factor Jun/AP-1 in the regulation of the Alzheimer's beta-amyloid precursor protein gene. , 1994, The Journal of biological chemistry.

[61]  W. Engel,et al.  Increase of nitric oxide synthases and nitrotyrosine in inclusion‐body myositis , 1996, Neuroreport.

[62]  W. Engel,et al.  Three lipoprotein receptors and cholesterol in inclusion-body myositis muscle , 2002, Neurology.

[63]  R. Kopito,et al.  Aggresomes: A Cellular Response to Misfolded Proteins , 1998, The Journal of cell biology.

[64]  V. Askanas,et al.  Cystatin C colocalizes with amyloid‐β and coimmunoprecipitates with amyloid‐β precursor protein in sporadic inclusion‐body myositis muscles , 2003 .

[65]  E. Sztul,et al.  Hassles with Taking Out the Garbage: Aggravating Aggresomes , 2002, Traffic.

[66]  F. Mastaglia,et al.  Inflammatory myopathies: Clinical, diagnostic and therapeutic aspects , 2003, Muscle & nerve.

[67]  W. Engel,et al.  Immunocytochemical localization of ubiquitin in inclusion body myositis allows its light‐microscopic distinction from polymyositis , 1992, Neurology.

[68]  W. Engel,et al.  Transfer of beta-amyloid precursor protein gene using adenovirus vector causes mitochondrial abnormalities in cultured normal human muscle. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[69]  P. Crofton,et al.  Diagnostic Utility of a Low-Dose Gonadotropin-Releasing Hormone Test in the Context of Puberty Disorders , 2004, Hormone Research in Paediatrics.

[70]  G. Vattemi,et al.  Mutant ubiquitin UBB+1 is accumulated in sporadic inclusion-body myositis muscle fibers , 2004, Neurology.

[71]  W. Engel,et al.  Inclusion-body myositis and myopathies: different etiologies, possibly similar pathogenic mechanisms , 2002, Current opinion in neurology.

[72]  R. Rosenberg.  The molecular and genetic basis of AD: The end of the beginning , 2000, Neurology.