Molecular mechanism of ALS and a possible gene therapy

Koji Abe, Hitoshi Warita

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


We report clinical characteristics of familial amyotrophic lateral sclerosis (FALS) with four different missense point mutations in exons 1, 2, 4, and 5 of the Cu/Zn superoxide dismutase (SOD) gene, that result in amino acid substitutions of cysteine 6 by phenylalanin (C 6 F), histidine 46 by arginine (H46R), leucine 84 by valine (L84V), isoleucine 104 by phenylalanine (I104F), and valine 148 by isoleucine (V148I), in five Japanese families. Although features of progressive neurogenic muscular atrophy was common in patients of these families, patients of each family showed characteristic clinical features. Immunoreactivity for Cu/Zn SOD of the motor neurons was not different between the ALS and controls. In contrast, immunoreactivity for NT was densely detected in motor neurons of ALS while that was not or was only minimally detected in those of controls. Adenovirus-mediated E. coli LacZ gene was transferred and expressed both in the muscle and spinal cord of transgenic mice. These results suggest that familial ALS with different mutations of the Cu/Zn SOD gene showed each clinical characteristics, that nitration of protein-tyrosine residue is upregulated in motor neurons of the spinae cord of ALS, and that there could be a possible future therapy of ALS with exogenous gene transfer.

Original languageEnglish
Pages (from-to)68-69
Number of pages2
JournalClinical Neurology
Issue number1
Publication statusPublished - Jun 10 1999


  • Amyotrophic lateral sclerosis
  • Gene therapy
  • Nitric oxide
  • Superoxide dismutase

ASJC Scopus subject areas

  • Clinical Neurology


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