Advanced glycation endproducts are deposited in neuronal hyaline inclusions: A study on familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation

Noriyuki Shibata, Asao Hirano, Shinsuke Kato, Ryoji Nagai, Seikoh Horiuchi, Takashi Komori, Takahiko Umahara, Kohtaro Asayama, Makio Kobayashi

Research output: Contribution to journalArticle

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To determine the role of advanced glycation endproducts (AGE) in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) with superoxide dismutase-l (SOD1) mutation, we investigated the immunohistochemical localization of Nε-carboxymethyl-lysine (CML), one of the major AGE structures, in spinal cords from three familial ALS patients with a heterozygous Ala to Val substitution at codon 4 in the gene for SOD1. Neuronal hyaline inclusions (NHIs), the abnormal structures seen in some of the remaining lower motor neurons of familial ALS patients with SOD1 mutation, were intensely stained by a monoclonal antibody specific for CML in contrast to the only weakly stained cytoplasm. Inmunoelectron microscopy depicted the CML determinants restricted to the granule-associated thick linear structures that mainly compose the NHIs. The NHIs were also recognized by antibodies to SOD1, phosphorylated neurofilament protein and ubiquitin. No focal collection of either CML or SOD1 was found in neurons of the control individuals. Our results indicate that CML is a component of the NHIs of familial ALS patients with SOD1 mutation, and suggest that the CML formation may be mediated by protein glycoxidation or lipid peroxidation in the presence of oxidative stress from mutant SOD1, in association with motor neuron degeneration.

Original languageEnglish (US)
Pages (from-to)240-246
Number of pages7
JournalActa neuropathologica
Issue number3
Publication statusPublished - Mar 1 1999



  • Advanced glycation endproducts
  • Amyotrophic lateral sclerosis
  • Hyaline inclusions
  • Immunohistochemistry
  • Superoxide dismutase

ASJC Scopus subject areas

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

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