Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis

Arie Gruzman, William L. Wood, Evgenia Alpert, M. Dharma Prasad, Robert G. Miller, Jeffery D. Rothstein, Robert Bowser, Ronald Hamilton, Troy D. Wood, Don W. Cleveland, Vishwanath R. Lingappa, Jian Liu

Research output: Contribution to journalArticlepeer-review

149 Scopus citations


Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron degenerative disease whose etiology and pathogenesis remain poorly understood. Most cases of ALS (≈90%) are sporadic (SALS), occurring in the absence of genetic associations. Approximately 20% of familial ALS (FALS) cases are due to known mutations in the copper, zinc superoxide dismutase (SOD1) gene. Molecular evidence for a common pathogenesis of SALS and FALS has remained elusive. Here we use covalent chemical modification to reveal an attribute of spinal cord SOD1 common to both SOD1-linked FALS and SALS, but not present in normal or disease-affected tissues from other neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases and spinal muscular atrophy, a non-ALS motor neuron disease. Biotinylation reveals a 32-kDa, covalently cross-linked SOD1-containing protein species produced not only in FALS caused by SOD1 mutation, but also in SALS. These studies use chemical modification as a novel tool for the detection of a disease-associated biomarker. Our results identify a shared molecular event involving a known target gene and suggest a common step in the pathogenesis between SALS and FALS.

Original languageEnglish (US)
Pages (from-to)12524-12529
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number30
StatePublished - Jul 24 2007


  • Copper, zinc superoxide dismutase
  • Motor neuron
  • Neurodegeneration

ASJC Scopus subject areas

  • General


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