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Vascular Occlusion Training for Inclusion Body Myositis: A Novel Therapeutic Approach
Published on: June 5, 2010
Molecular pathology and pathogenesis of inclusion-body myositis
Valerie Askanas1, W King Engel
1USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, California 90017-1912, USA. askanas@usc.edu
Abstract:
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-beta precursor protein (AbetaPP), and accumulation of its proteolytic fragment Abeta; 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 AbetaPP within the aging muscle fibers is an early upstream event causing a subsequent pathogenic cascade.
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