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Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer’s and Parkinson’s disease brains

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Abstract

Sporadic inclusion-body myositis (s-IBM), the most common muscle disease of older persons, is of unknown cause and lacks successful treatment. Here we summarize diagnostic criteria and discuss our current understanding of the steps in the pathogenic cascade. While it is agreed that both degeneration and mononuclear-cell inflammation are components of the s-IBM pathology, how each relates to the pathogenesis remains unsettled. We suggest that the intra-muscle-fiber degenerative component plays the primary role, leading to muscle-fiber destruction and clinical weakness, since anti-inflammatory treatments are not of sustained benefit. We discuss possible treatment strategies aimed toward ameliorating a degenerative component, for example, lithium and resveratrol. Also discussed are the intriguing phenotypic similarities between s-IBM muscle fibers and the brains of Alzheimer and Parkinson’s diseases, the most common neurodegenerative diseases associated with aging. Similarities include, in the respective tissues, cellular aging, mitochondrial abnormalities, oxidative and endoplasmic-reticulum stresses, proteasome inhibition and multiprotein aggregates.

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Acknowledgments

This work was supported in parts by grants (to VA) from the National Institutes of Health (NS31836, NS34103 and AG16768 Merit Award), the Muscular Dystrophy Association, The Myositis Association (to VA) and the Helen Lewis Research Fund. We thank our many research-team colleagues who participated over the years in the studies described herein. The most recent collaborators include A. Nogalska, C. Terracciano, S. Wojcik, O. Paciello and C. D’Agostino.

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  1. Department of Neurology, USC Neuromuscular Center, Good Samaritan Hospital, University of Southern California Keck School of Medicine, 637 South Lucas Avenue, Los Angeles, CA, 90017-1912, USA

    Valerie Askanas & W. King Engel

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  1. Valerie Askanas
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Correspondence to Valerie Askanas.

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Askanas, V., Engel, W.K. Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer’s and Parkinson’s disease brains. Acta Neuropathol 116, 583–595 (2008). https://doi.org/10.1007/s00401-008-0449-0

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