New consensus research on neuropathological aspects of familial amyotrophic lateral sclerosis with superoxide dismutase 1 (SOD1) gene mutations: Inclusions containing SOD1 in neurons and astrocytes

Shinsuke Kato, Miki Takikawa, Kenji Nakashima, Asao Hirano, Don W. Cleveland, Hirofumi Kusaka, Noriyuki Shibata, Masako Kato, Imaharu Nakano, Eisaku Ohama

Research output: Contribution to journalReview article

120 Scopus citations


Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily involves the motor neuron system. Approximately 5-10% of ALS is familial. Superoxide dismutase 1 (SOD1) gene mutations are shown to be associated with about 20% of familial ALS (FALS) patients. The neuronal Lewy-body-like hyaline inclusion (LBHI) and astrocytic hyaline inclusion (Ast-HI) are morphological hallmarks of certain SOD1-linked FALS patients with SOD1 gene mutant and transgenic mice expressing human SOD1 with G85R mutation. From the detailed immunohistochemic analyses, the essential common protein of both inclusions is SOD1. Ultrastructurally, both inclusions consist of granule-coated fibrils 15-25 nm in diameter. Based on the immuno-electron microscopical finding that these abnormal granulecoated fibrils are positive for SOD1, the formation (or aggregation) of the abnormal fibrils containing SOD1 would be essential evidence in diseases caused by various SOD1 mutations. The granule-coated fibrils are also modified by advanced glycation end products (AGEs). The AGEs themselves are insoluble molecules with direct toxic effects on cells. AGE formation of SOD1 composing the granule-coated fibrils (probable AGE-modified mutant SOD1) may amplify their aggregation and produce a more marked toxicity. (ALS 2000; 1:163-184)

Original languageEnglish (US)
Pages (from-to)163-184
Number of pages22
JournalAmyotrophic Lateral Sclerosis
Issue number3
StatePublished - Dec 1 2000



  • Familial Amyotrophic Lateral Sclerosis (FLAS) Neuronal Lewy-BODY-LIKE Hyaline Inclusions (LBHIS) Astrocytic Hyaline Inclusions (AST-HIS) Superoxide Dismutase 1 (SOD1) Granule-COATED Fibris

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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