Optineurin is potentially associated with TDP-43 and involved in the pathogenesis of inclusion body myositis

Neuropathol Appl Neurobiol. 2013 Jun;39(4):406-16. doi: 10.1111/j.1365-2990.2012.01297.x.


Aims: Increasing evidences suggest a similarity in the pathophysiological mechanisms of neuronal cell death in amyotrophic lateral sclerosis (ALS) and myofibre degeneration in sporadic inclusion body myositis (sIBM). The aim of this study is to elucidate the involvement of ALS-causing proteins in the pathophysiological mechanisms in sIBM.

Methods: Skeletal muscle biopsy specimens of five patients with sIBM, two with oculopharyngeal muscular dystrophy (OPMD), three with polymyositis (PM), three with dermatomyositis (DM), three with neurogenic muscular atrophy, and three healthy control subjects were examined. We analysed the expression and localization of familial ALS-causing proteins, including transactive response DNA binding protein-43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), Cu/Zn superoxide dismutase (SOD1) and optineurin (OPTN) by immunohistochemistry.

Results: TDP-43, OPTN and, to a lesser extent, FUS/TLS were more frequently accumulated in the cytoplasm in patients with sIBM and OPMD than in patients with PM, DM, neurogenic muscular atrophy, or healthy control subjects. SOD1 was accumulated in a small percentage of myofibres in patients with sIBM and OPMD, and to a very small extent in patients with PM and DM. Confocal microscopy imaging showed that TDP-43 proteins more often colocalized with OPTN than with FUS/TLS, p62 and phosphorylated Tau.

Conclusions: These findings suggest that OPTN in cooperation with TDP-43 might be involved in the pathophysiological mechanisms of skeletal muscular degeneration in myopathy with rimmed vacuoles. Further investigation into these mechanisms is therefore warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / pathology
  • Biopsy
  • Cell Cycle Proteins
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Dermatomyositis / genetics
  • Dermatomyositis / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Transport Proteins
  • Middle Aged
  • Muscular Atrophy / genetics
  • Muscular Atrophy / pathology
  • Muscular Dystrophy, Oculopharyngeal / genetics
  • Muscular Dystrophy, Oculopharyngeal / pathology
  • Myositis, Inclusion Body / genetics*
  • Myositis, Inclusion Body / pathology*
  • Polymyositis / genetics
  • Polymyositis / pathology
  • RNA-Binding Protein FUS / metabolism
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • TDP-43 Proteinopathies / genetics*
  • TDP-43 Proteinopathies / pathology*
  • Transcription Factor TFIIIA / genetics
  • Transcription Factor TFIIIA / physiology*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Membrane Transport Proteins
  • OPTN protein, human
  • RNA-Binding Protein FUS
  • SOD1 protein, human
  • Transcription Factor TFIIIA
  • Superoxide Dismutase
  • Superoxide Dismutase-1