Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body myositis, regenerating and necrotic muscle fibers, and at neuromuscular junctions

J Neuropathol Exp Neurol. 2000 Jul;59(7):592-8. doi: 10.1093/jnen/59.7.592.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Fluorescent Antibody Technique
  • Humans
  • Inclusion Bodies / chemistry
  • Inclusion Bodies / pathology
  • Microscopy, Immunoelectron
  • Muscle Fibers, Skeletal / pathology*
  • Muscle Fibers, Skeletal / physiology
  • Muscle Fibers, Skeletal / ultrastructure
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / physiology
  • Myositis, Inclusion Body / pathology*
  • Necrosis
  • Nerve Tissue Proteins / analysis*
  • Neuromuscular Junction / pathology*
  • Neuromuscular Junction / ultrastructure
  • Regeneration
  • Synucleins
  • alpha-Synuclein

Substances

  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein