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, Jeffrey D Rothstein, Robert Bowser, Ronald Hamilton, Troy D. Wood, Don W. Cleveland, Vishwanath R. Lingappa, Jian Liu

Research output: Contribution to journalArticle

Abstract

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
Volume104
Issue number30
DOIs
StatePublished - Jul 24 2007

Fingerprint

Motor Neuron Disease
Biotinylation
Spinal Muscular Atrophy
Mutation
Huntington Disease
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Genes
Superoxide Dismutase
Parkinson Disease
Zinc
Copper
Spinal Cord
Alzheimer Disease
Biomarkers
Amyotrophic lateral sclerosis 1

Keywords

  • Copper, zinc superoxide dismutase
  • Motor neuron
  • Neurodegeneration

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis. / Gruzman, Arie; Wood, William L.; Alpert, Evgenia; Prasad, M. Dharma; Miller, Robert G.; Rothstein, Jeffrey D; Bowser, Robert; Hamilton, Ronald; Wood, Troy D.; Cleveland, Don W.; Lingappa, Vishwanath R.; Liu, Jian.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 30, 24.07.2007, p. 12524-12529.

Research output: Contribution to journalArticle

Gruzman, A, Wood, WL, Alpert, E, Prasad, MD, Miller, RG, Rothstein, JD, Bowser, R, Hamilton, R, Wood, TD, Cleveland, DW, Lingappa, VR & Liu, J 2007, 'Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 30, pp. 12524-12529. https://doi.org/10.1073/pnas.0705044104
Gruzman, Arie ; Wood, William L. ; Alpert, Evgenia ; Prasad, M. Dharma ; Miller, Robert G. ; Rothstein, Jeffrey D ; Bowser, Robert ; Hamilton, Ronald ; Wood, Troy D. ; Cleveland, Don W. ; Lingappa, Vishwanath R. ; Liu, Jian. / Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 30. pp. 12524-12529.
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