Superoxide dismutase-1 mutation-related neurotoxicity in familial amyotrophic lateral sclerosis

Noriyuki Shibata, Asao Hirano, T. Yamamoto, Y. Kato, Makio Kobayashi

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations


Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron system involvement, and is epidemiologically subclassified into sporadic, familial and endemic forms. About 20% of ALS families are associated with mutations in the gene for superoxide dismutase-1 (SOD1) encoded on chromosome 21q22.1. Several studies have pointed to a variety of functions of mutant SOD1, which has enhanced catalytic activity of the peroxynitrite-mediated tyrosine nitration, readily releases the reactive Cu ions, induces apoptotic cell death, has enhanced peroxidase activity, damages the mitochondria to release Ca 2+ , SOD1-containing aggregates in the cytoplasm. Many of these studies have obtained evidence for increased oxidative damage in ALS. On the other hand, some reports disagree with oxidative damage involvement in SOD1 mutant ALS. In considering the findings of increased oxidative damage in mutant SOD1- expressing transgenic mice, it should be remembered that overexpression of mutant SOD1 may enhance oxidative stress generation from this enzyme. In this review, we present the clinicopathological features of SOD1 mutant familial ALS and its transgenic mouse model, and also discuss SOD1 mutation-related neurotoxicity, including SOD1 protein aggreand forms gation and post-translational protein modification. (ALS 2000; 1:143-161)

Original languageEnglish (US)
Pages (from-to)143-161
Number of pages19
JournalAmyotrophic Lateral Sclerosis
Issue number3
StatePublished - Dec 1 2000


  • amyotrophic lateral sclerosis post-translational protein modification protein aggregation superoxide dismutase transgenic mouse model

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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