HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: 01.wnl.0000192128.13875.1ev1 66/1_suppl_1/S39    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Askanas, V. Articles by Engel, W. K. Search for Related Content PubMed PubMed Citation Articles by Askanas, V. Articles by Engel, W. K.

Inclusion-body myositis

A myodegenerative conformational disorder associated with Aβ, protein misfolding, and proteasome inhibition

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.

This article has been cited by other articles:

				C C Weihl, P Temiz, S E Miller, G Watts, C Smith, M Forman, P I Hanson, V Kimonis, and A Pestronk TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia J. Neurol. Neurosurg. Psychiatry, October 1, 2008; 79(10): 1186 - 1189. [Abstract] [Full Text] [PDF]

				J. Schmidt and M. C. Dalakas Inflammation interrelates to APP in sIBM: IL-1{beta} induces accumulation of {beta}-amyloid Brain, July 24, 2008; (2008) awn164v1. [Full Text] [PDF]

				J. Schmidt, K. Barthel, A. Wrede, M. Salajegheh, M. Bahr, and M. C. Dalakas Interrelation of inflammation and APP in sIBM: IL-1{beta} induces accumulation of {beta}-amyloid in skeletal muscle Brain, May 1, 2008; 131(5): 1228 - 1240. [Abstract] [Full Text] [PDF]

				X. Chen, O. Ghribi, and J. D. Geiger Rabbits fed cholesterol-enriched diets exhibit pathological features of inclusion body myositis Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R829 - R835. [Abstract] [Full Text] [PDF]

				S. A. Greenberg Proposed immunologic models of the inflammatory myopathies and potential therapeutic implications Neurology, November 20, 2007; 69(21): 2008 - 2019. [Abstract] [Full Text] [PDF]

				M. C. V. Malicdan, S. Noguchi, I. Nonaka, Y. K. Hayashi, and I. Nishino A Gne knockout mouse expressing human GNE D176V mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy Hum. Mol. Genet., November 15, 2007; 16(22): 2669 - 2682. [Abstract] [Full Text] [PDF]

				M. Salajegheh, G. Rakocevic, R. Raju, A. Shatunov, L. G. Goldfarb, and M. C. Dalakas T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis Neurology, October 23, 2007; 69(17): 1672 - 1679. [Abstract] [Full Text] [PDF]

				M. C. V. Malicdan, S. Noguchi, I. Nonaka, Y. K. Hayashi, and I. Nishino A Gne knockout mouse expressing human V572L mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy Hum. Mol. Genet., January 15, 2007; 16(2): 115 - 128. [Abstract] [Full Text] [PDF]

				W. K. Engel and V. Askanas Inclusion-body myositis: Clinical, diagnostic, and pathologic aspects Neurology, January 24, 2006; 66(1_suppl_1): S20 - S29. [Abstract] [Full Text] [PDF]