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Optineurin is potentially associated with TDP‐43 and involved in the pathogenesis of inclusion body myositis
Author(s) -
Yamashita S.,
Kimura E.,
Tawara N.,
Sakaguchi H.,
Nakama T.,
Maeda Y.,
Hirano T.,
Uchino M.,
Ando Y.
Publication year - 2013
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2012.01297.x
Subject(s) - optineurin , pathology , pathogenesis , amyotrophic lateral sclerosis , sod1 , polymyositis , medicine , oculopharyngeal muscular dystrophy , inclusion body myositis , muscle biopsy , biology , biopsy , muscular dystrophy , disease
S. Yamashita, E. Kimura, N. Tawara, H. Sakaguchi, T. Nakama, Y. Maeda, T. Hirano, M. Uchino and Y. Ando (2013) Neuropathology and Applied Neurobiology 39, 406–416 Optineurin is potentially associated with TDP‐43 and involved in the pathogenesis of inclusion body myositis 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.