Published online before print December 16, 2005, doi:10.1212/01.wnl.0000192128.13875.1e)
NEUROLOGY 2006;66:S39-S48
© 2006 American Academy of Neurology
Inclusion-body myositisA myodegenerative conformational disorder associated with Aβ, protein misfolding, and proteasome inhibition
Valerie Askanas, MD, PhD and
W. King Engel, MD
From the USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA.
Address correspondence and reprint requests to Dr. Valerie Askanas, USC Neuromuscular Center, Good Samaritan Hospital, 637 S. Lucas Ave, Los Angeles, CA 90017-1912; e-mail: askanas{at}usc.edu
Sporadic inclusion-body myositis (s-IBM), the most common muscle disease of older persons, is of unknown cause and there is no successful treatment. We summarize our most recent findings, which provide a better understanding of the steps in the pathogenetic cascade. We suggest that s-IBM is primarily a myodegenerative disease. Intriguing are the phenotypic similarities between s-IBM muscle fibers and the brains of Alzheimer disease, the most common neurodegenerative disease of older persons. In s-IBM, abnormal accumulation of the amyloid-β (Aβ) precursor protein and its proteolytic fragment, Aβ, associated with the aging intracellular milieu of the muscle fiber, appear to be key upstream pathogenic events. We propose that the identified abnormal accumulation, misfolding, and aggregation of proteins, perhaps provoked by the aging milieu and aggravated by the oxidative stress, lead to the s-IBM-specific vacuolar degeneration and atrophy of muscle fibers.
This article was previously published in electronic format as an Expedited E-Pub at www.neurology.org.
Supported by grants 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.
Disclosure: The authors report no conflicts of interest.
Received June 22, 2005. Accepted in final form October 14, 2005.
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