Nuclear contour irregularity and abnormal transporter protein distribution in anterior horn cells in amyotrophic lateral sclerosis

Yoshimi Kinoshita, Hidefumi Ito, Asao Hirano, Kengo Fujita, Reika Wate, Masataka Nakamura, Satoshi Kaneko, Satoshi Nakano, Hirofumi Kusaka

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


The nucleocytoplasmic transport system is essential for maintainingcell viability; transport of proteins and nucleic acids between the nucleus and the cytoplasm occurs through nuclear pore complexes (NPCs). In this study, we examined the immunohistochemical distribution of the major protein components of NPCs, Nup62, Nup88, and Nup153, in spinal cords from controls and patients with sporadic or familial amyotrophic lateral sclerosis (SALS or FALS) and its mouse model. In control subjects, immunolabeling on thenuclear envelopes of anterior horn cells (AHCs) was invariably smooth and continuous, whereas in SALS and FALS patients, the AHCs predominantly showed irregular nuclear contours. Double immunofluorescence staining demonstrated that in SALS patients, importin-β immunoreactivity was absent in the nuclei in a subset of AHCs; in these cells, Nup62 immunolabeling of nuclear membrane was invariably irregular, suggesting that there was dysfunctional nucleocytoplasmic transport in those AHCs. In the mouse model, Nup62-immunolabeled AHCs with irregular nuclear contours were predominant as early as the presymptomatic stage and the contours became progressively discontinuous along with disease development. Together, these observations suggest that dysfunctional nucleocytoplasmic transport may underlie the pathogenesis of ALS.

Original languageEnglish (US)
Pages (from-to)1184-1192
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Issue number11
StatePublished - Nov 2009
Externally publishedYes


  • Amyotrophic lateral sclerosis
  • Nuclear contour irregularity
  • Nuclear pore complex
  • Nucleocytoplasmic transport system
  • Nucleoporin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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