Paired helical filaments of inclusion-body myositis muscle contain RNA and survival motor neuron protein.
Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older persons. Pathologically, the muscle biopsy manifests various degrees of inflammation and specific vacuolar degeneration of muscle fibers characterized by paired helical filaments (PHFs) composed of phosphorylated tau. IBM vacuolated fibers also contain accumulations of several other Alzheimer-characteristic proteins. Molecular mechanisms leading to formation of the PHFs and accumulations of proteins in IBM muscle are not known. We report that the abnormal muscle fibers of IBM contained (i) acridine-orange-positive RNA inclusions that colocalized with the immunoreactivity of phosphorylated tau and (ii) survival motor neuron protein immunoreactive inclusions, which by immuno-electron microscopy were confined to paired helical filaments. This study demonstrates two novel components of the IBM paired helical filaments, which may lead to better understanding of their pathogenesis.
Broccolini
A
A
University of Southern California Neuromuscular Center, Los Angeles, California 90017-1712, USA.
Engel
W K
WK
Alvarez
R B
RB
Askanas
V
V
D000165:Acridine Orange; D000911:Antibodies, Monoclonal; D017362:Cyclic AMP Response Element-Binding Protein; D005456:Fluorescent Dyes; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009132:Muscles / Q000378:metabolism*; D018979:Myositis, Inclusion Body / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019600:Neuropil Threads / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D013194:Staining and Labeling; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D017362:Cyclic AMP Response Element-Binding Protein; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D012313:RNA; D000165:Acridine Orange