title: Sporadic inclusion-body myositis: A degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy.
abstract: Sporadic inclusion-body myositis (s-IBM) is the most common degenerative muscle disease in which aging appears to be a key risk factor. In this review we focus on several cellular molecular mechanisms responsible for multiprotein aggregation and accumulations within s-IBM muscle fibers, and their possible consequences. Those include mechanisms leading to: a) accumulation in the form of aggregates within the muscle fibers, of several proteins, including amyloid-β42 and its oligomers, and phosphorylated tau in the form of paired helical filaments, and we consider their putative detrimental influence; and b) protein misfolding and aggregation, including evidence of abnormal myoproteostasis, such as increased protein transcription, inadequate protein disposal, and abnormal posttranslational modifications of proteins. Pathogenic importance of our recently demonstrated abnormal mitophagy is also discussed. The intriguing phenotypic similarities between s-IBM muscle fibers and the brains of Alzheimer and Parkinson's disease patients, the two most common neurodegenerative diseases associated with aging, are also discussed. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
authors.affiliation: USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA, USA. Electronic address: askanas@usc.edu.
authors.forename: Valerie
authors.initials: V
authors.lastname: Askanas
authors.affiliation: USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA, USA.
authors.forename: W King
authors.initials: WK
authors.lastname: Engel
authors.affiliation: USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Nogalska
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D057165:Proteostasis Deficiencies / Q000378:metabolism / Q000401:mortality
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Aging; Amyloid-β42; Autophagy; Inclusion-body myositis; Mitophagy; Multiprotein aggregates