Sporadic inclusion-body myositis: a proposed key pathogenetic role of the abnormalities of the ubiquitin-proteasome system, and protein misfolding and aggregation.
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 in s-IBM muscle fibers, which demonstrate abnormalities of the ubiquitin-proteasome system, and abnormal accumulation, misfolding and aggregation of proteins. We propose that these changes, possibly provoked by the aging intra-muscle fiber cellular milieu, and aggravated by the oxidative stress, play a key pathogenic role in s-IBM. This evidence strongly suggests that mechanisms other than the immune/inflammatory response play the important role in s-IBM muscle fiber degeneration.
Askanas
V
V
USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, California 90017-1912, USA. askanas@hsc.usc.edu
Engel
W King
WK
D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D018979:Myositis, Inclusion Body / Q000209:etiology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D017510:Protein Folding; D025801:Ubiquitin / Q000502:physiology*; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D006360:Heat-Shock Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein