Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body myositis, regenerating and necrotic muscle fibers, and at neuromuscular junctions.
Alpha-synuclein (alpha-syn) is an important component of neuronal and glial inclusions in brains of patients with several neurodegenerative disorders. Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older patients. Its muscle phenotype shows several similarities with Alzheimer disease brain. A distinct feature of s-IBM pathology is specific vacuolar degeneration of muscle fibers characterized by intracellular amyloid inclusions formed by both amyloid-beta (Abeta) and paired-helical filaments composed of phosphorylated tau. We immunostained alpha-syn in muscle biopsies of s-IBM, disease-control, and normal patients. Approximately 60% of Abeta-positive vacuolated muscle fibers (VMF) contained well-defined inclusions immunoreactive with antibodies against alpha-syn. In those fibers. alpha-syn co-localized with Abeta, both by light microscopy, and ultrastructurally. Paired-helical filaments did not contain alpha-syn immunoreactivity. In all muscle biopsies, alpha-syn was strongly immunoreactive at the postsynaptic region of the neuromuscular junctions. alpha-syn immunoreactivity also occurred diffusely in regenerating and necrotic muscle fibers. In cultured human muscle fibers, alpha-syn and its mRNA were expressed by immunocytochemistry, immunoblots, and Northern blots. Our study provides the first demonstration that alpha-syn participates in normal and pathologic processes of human muscle. Therefore. its function is not exclusive to the brain and neurodegenerative diseases.
Askanas
V
V
USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912, USA.
Engel
W K
WK
Alvarez
R B
RB
McFerrin
J
J
Broccolini
A
A
D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000473:pathology; D016253:Microscopy, Immunoelectron; D018485:Muscle Fibers, Skeletal / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000473:pathology* / Q000502:physiology; D018979:Myositis, Inclusion Body / Q000473:pathology*; D009336:Necrosis; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009469:Neuromuscular Junction / Q000473:pathology* / Q000648:ultrastructure; D012038:Regeneration; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein