Neuronal NOS is dislocated during muscle atrophy in amyotrophic lateral sclerosis

Naoki Suzuki, Hideki Mizuno, Hitoshi Warita, Shin'ichi Takeda, Yasuto Itoyama, Masashi Aoki

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Previously, we demonstrated that neuronal nitric oxide synthase (nNOS) is activated and promotes muscle atrophy in skeletal muscle during tail suspension, a model of unloading and denervation. Here, we examined patients with amyotrophic lateral sclerosis (ALS) and mutant (H46R) SOD1 transgenic (Tg) mice model using immunohistochemistry, Western blotting and real time PCR. We found cytoplasmic nNOS staining of angulated muscle fibers in patients with ALS. We also examined mutant SOD1 Tg mice and found cytoplasmic nNOS staining even before the onset of clinical muscle atrophy. In the Tg mice, nNOS was largely extracted with 100 mM NaCl and barely detected in the pellet fraction, suggesting fragile anchoring of nNOS to the sarcolemma. We also showed an elevated expression of atrogin-1, key molecules in muscle atrophy at the end stage. A common nNOS dislocation/atrogin-1/muscle atrophy pathway among tail suspension, denervation and ALS is suggested. nNOS modulation therapy may be beneficial in several types of muscle atrophy.

Original languageEnglish
Pages (from-to)95-101
Number of pages7
JournalJournal of the neurological sciences
Issue number1-2
Publication statusPublished - 2010 Jul 15


  • Amyotrophic lateral sclerosis (ALS)
  • Motor neuron disease (MND)
  • Muscle atrophy
  • Neuronal nitric oxide synthase (nNOS)
  • Superoxide dismutase (SOD1)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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